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Kraus, William Erle

Overview:

My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation.  My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I practice as a preventive cardiologist with a focus on cardiometabolic risk and exercise physiology for older athletes.  My research space has both a basic wet laboratory component and a human integrative physiology one.

One focus of our work is an integrative physiologic examination of exercise effects in human subjects in clinical studies of exercise training in normal individuals, in individuals at risk of disease (such as pre-diabetes and metabolic syndrome; STRRIDE), and in individuals with disease (such as coronary heart disease, congestive heart failure and cancer).

A second focus of my research group is exploration of genetic determinates of disease risk in human subjects.  We conduct studies of early onset cardiovascular disease (GENECARD; CATHGEN), congestive heart failure (HF-ACTION), peripheral arterial disease (AMNESTI), and metabolic syndrome.  We are exploring analytic models of predicting disease risk using established and innovative statistical methodology.

A third focus of my group’s work is to understand the cellular signaling mechanisms underlying the normal adaptive responses of skeletal muscle to physiologic stimuli, such as occur in exercise conditioning, and to understand the abnormal maladaptive responses that occur in response to pathophysiologic stimuli, such as occur in congestive heart failure, aging and prolonged exposure to microgravity.

Recently we have begun to investigate interactions of genes and lifestyle interventions on cardiometabolic outcomes.  We have experience with clinical lifestyle intervention studies, particularly the contributions of genetic variants to interventions responses.  We call this Lifestyle Medicopharmacogenetics.

KEY WORDS:

exercise, skeletal muscle, energy metabolism, cell signaling, gene expression, cell stretch, heart failure, aging, spaceflight, human genetics, early onset cardiovascular disease, lifestyle medicine

Positions:

Professor of Medicine

Medicine, Cardiology
School of Medicine

Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Professor in the School of Nursing

School of Nursing
School of Nursing

Member of Duke Molecular Physiology Institute

Duke Molecular Physiology Institute
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1982

M.D. — Duke University

Medical Resident, Medicine

Duke University

Fellow In Cardiology, Medicine

Duke University

News:

Grants:

Molecular Transducers of Physical Activity and Health: NC Consortium Clinical Site

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 06, 2016
End Date
November 30, 2022

Behavioral and Physiology in Aging

Administered By
Center for the Study of Aging and Human Development
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2015
End Date
August 31, 2020

Exercise and Pharmacotherapy for Anxiety in Cardiac Patients

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
August 01, 2015
End Date
July 31, 2020

Facility and Web-based Approaches to Lifestyle Change in Resistant Hypertension

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
December 01, 2014
End Date
November 30, 2019

Biomarkers of Caloric Restriction in Humans: the CALERIE Biorepository

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 15, 2015
End Date
May 31, 2019

Duke KURe Program

Administered By
Obstetrics and Gynecology, Urogynecology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
August 01, 2013
End Date
July 31, 2018

Determine the methylation profile of DNA samples II

Administered By
Duke Molecular Physiology Institute
AwardedBy
Environmental Protection Agency
Role
Principal Investigator
Start Date
February 02, 2017
End Date
August 01, 2017

Determine the Methylation Profile of DNA Samples

Administered By
Duke Molecular Physiology Institute
AwardedBy
Environmental Protection Agency
Role
Principal Investigator
Start Date
July 01, 2016
End Date
June 30, 2017

Circulatory system and integrated muscle tissue for drug and tissue toxicity

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 24, 2012
End Date
June 30, 2017

University Training Program in Biomolecular and Tissue Engineering

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1994
End Date
June 30, 2017

Lifestyle, CVD Risk and Cognitive Impairment

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2011
End Date
April 30, 2017

Ranolazine and Exercise

Administered By
Duke Molecular Physiology Institute
AwardedBy
Gilead Sciences, Inc.
Role
Principal Investigator
Start Date
August 07, 2013
End Date
March 31, 2017

Effects of Chondroitin Sulfate and Chrondroitin Sulfate/Glucosamine on Muscle Immune Signaling and Function in TNF-alpha Stimulated Three Dimensional Muscle Cultures

Administered By
Biomedical Engineering
AwardedBy
Bioiberica, S.A.
Role
Co Investigator
Start Date
February 15, 2016
End Date
February 14, 2017

Stress Management and Biomarkers of Risk in Cardiac Rehabilitation

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2009
End Date
November 30, 2016

A mHealth Strategy for Long-Term Care in Cardiac Rehabilitation Patients

Administered By
Duke Molecular Physiology Institute
AwardedBy
Vida Health
Role
Principal Investigator
Start Date
September 01, 2014
End Date
October 15, 2016

A Pilot Study in Healthy Male Volunteers to Evaluate a Skeletal-muscle Microbiopsy Technique

Administered By
Duke Molecular Physiology Institute
AwardedBy
GlaxoSmithKline
Role
Principal Investigator
Start Date
October 01, 2013
End Date
September 30, 2016

Metabolomic Quantitative Trait Locus (mQTL) Genetic Mapping in Human CVD

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 15, 2009
End Date
May 31, 2016

Bioiberica "Pre-Pilot Mobile App for OA"

Administered By
Duke Molecular Physiology Institute
AwardedBy
Bioiberica, S.A.
Role
Clinical Research Facilitator
Start Date
November 27, 2014
End Date
November 26, 2015

Mechanisms of Insulin Resistance in Rheumatoid Arthritis

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 05, 2008
End Date
August 31, 2015

Behavior And Physiology In Aging

Administered By
Center for the Study of Aging and Human Development
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1999
End Date
August 31, 2015

Exercise Dose-Response Effects in Prediabetes:Responses and Mechanisms

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 29, 2009
End Date
March 31, 2015

Dietary Nitrate to Augment Exercise Training Benefits in DM+PAD

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
February 01, 2013
End Date
January 31, 2015

CALERIE

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2009
End Date
December 31, 2014

CALERIE Non-competing Extension with Funds

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2002
End Date
December 31, 2014

Increased Plasma Nitrite, Tissue Oxygenation and Functional Changes in PAD

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
February 16, 2012
End Date
March 31, 2014

Aerobic Training During or After Adjuvant Therapy: A Randomized Trial

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 20, 2012
End Date
February 14, 2014

Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2010
End Date
February 14, 2014

Phase III Trial of Exercise Training in Postsurgical Lung Cancer

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
September 24, 2009
End Date
February 14, 2014

Multiwavelength Optical Emitter for Biomedical Diagnostics

Administered By
Duke Molecular Physiology Institute
AwardedBy
Valencell, INC
Role
Principal Investigator
Start Date
October 01, 2011
End Date
December 31, 2013

Analyses and reports of Cathgen database

Administered By
Duke Molecular Physiology Institute
AwardedBy
Environmental Protection Agency
Role
Principal Investigator
Start Date
May 15, 2012
End Date
September 30, 2013

Mechanisms of Insulin Resistance in Rheumatoid Arthritis

Administered By
Medicine, Rheumatology and Immunology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 05, 2008
End Date
August 31, 2013

The Role of Ankyrin-B Mutations in Premature Senescence

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 15, 2011
End Date
July 31, 2013

Peripheral endothelial and muscle cell pathology in cardiovascular disease

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 20, 2010
End Date
June 30, 2013

MicroRNA Mediation of Stretch-Induced Myoblast Function for Engineered Tissues

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2009
End Date
February 28, 2013

Mechanisms linking the adipogenic phenotype of aging muscle to insulin resistance

Administered By
Sarah Stedman Nutrition & Metabolism Center
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 15, 2006
End Date
August 31, 2012

Genetic modifiers of dilated cardiomyopathy in adult Drosophila

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 01, 2007
End Date
June 30, 2012

Genetic Mediators of Metabolic Cardiovascular Disease Risk

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2009
End Date
May 31, 2012

Candidate Genes and Longitudinal Disability Phenotypes

Administered By
Center for the Study of Aging and Human Development
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
May 15, 2006
End Date
April 30, 2012

Survival and Age Biases in Gene Associations with Coronary Disease

Administered By
School of Nursing
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 29, 2009
End Date
July 31, 2011

HF Action Supplement

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Communications Project Manager
Start Date
September 30, 2002
End Date
December 31, 2010

A CHF Trial Investigating Outcomes of Exercise Training

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2002
End Date
December 31, 2010

Advanced Haplotype Analyses in Coronary Artery Disease

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
August 02, 2004
End Date
June 30, 2010

Peripheral Effects of Exercise on Cardiovascular Health

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 15, 1998
End Date
December 31, 2009

Systems Biology of Angiogenesis

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
September 27, 2006
End Date
August 31, 2009

Changes in Functional Status Across Therapy for Primary Gilioma

Administered By
Radiation Oncology
AwardedBy
National Cancer Institute
Role
Consultant
Start Date
September 21, 2006
End Date
August 31, 2009

CALERIE

Administered By
Duke Clinical Research Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2002
End Date
August 31, 2009

Training in Biomolecular and Tissue Engineering

Administered By
Orthopaedics
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 20, 2003
End Date
June 30, 2009

Skeletal Muscle Plasticity Following LVAD Support

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
April 01, 2006
End Date
March 31, 2009

GENECARD: Gene identification in Early-Onset CAD

Administered By
Duke Molecular Physiology Institute
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2003
End Date
March 31, 2009

Comparative Approach to Genomics of Complex Traits

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 30, 2002
End Date
August 31, 2008

Angiogenesis and Mechanisms of Exercise Training in PAD

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 25, 2003
End Date
June 30, 2008

Duke Site Agreement for HF-ACTION trial

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 15, 2003
End Date
September 30, 2007

Insulin Resistance and Polycystic Ovary Syndrome

Administered By
Medicine, Endocrinology, Metabolism, and Nutrition
AwardedBy
National Institutes of Health
Role
Advisor
Start Date
September 15, 2002
End Date
July 31, 2007

Modifier Genes in Heart Failure

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 30, 2001
End Date
June 30, 2007

Promoting Health in Prostate and Breast Cancer Survivors

Administered By
School of Nursing
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
March 01, 2001
End Date
December 31, 2006

Mentored Clinical Research Scholar Program

Administered By
Medicine, Infectious Diseases
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 30, 2002
End Date
September 29, 2006

Stress & Myocardial Ischemia: Mechanisms & Treatment

Administered By
Psychiatry & Behavioral Sciences, Behavioral Medicine
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 05, 1998
End Date
August 31, 2006

STRENGTH: Survivor Training for Enhancing Total Health

Administered By
Surgery, Urology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 15, 2001
End Date
December 31, 2005

Differentiation and maintenance of skeletal and cardiac muscle in simulated microgravity

Administered By
Medicine, Cardiology
AwardedBy
National Aeronautics and Space Administration
Role
Principal Investigator
Start Date
December 01, 1999
End Date
November 30, 2003

Peripheral Effects Of Exercise On Cardiovascular Health

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 15, 1998
End Date
August 31, 2003

Differentiation And Maintenance Of Skeletal And Cardiac Mu

Administered By
Medicine, Cardiology
AwardedBy
National Aeronautics and Space Administration
Role
Principal Investigator
Start Date
March 01, 1999
End Date
November 30, 2002

Graduate Student Research Proposal for Amy Collinsworth (Cytoskeletal Contributions to Changes in Elasticity of Mammalia

Administered By
Biomedical Engineering
AwardedBy
National Aeronautics and Space Administration
Role
Co-Principal Investigator
Start Date
July 01, 1999
End Date
June 30, 2001

Regulation of Skeletal Muscle Development and Differentiation in Vitro by Mechanical

Administered By
Medicine, Cardiology
AwardedBy
National Aeronautics and Space Administration
Role
Principal Investigator
Start Date
September 01, 1995
End Date
September 02, 1999

Regulation Of Skeletal Muscle Development And Differentiat

Administered By
Medicine, Cardiology
AwardedBy
National Aeronautics and Space Administration
Role
Principal Investigator
Start Date
September 01, 1995
End Date
September 17, 1998

Molecular Signaling In Muscular Adaption To Exercise

Administered By
Medicine, Cardiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 1993
End Date
December 31, 1997

Regulation Of Skeletal Muscle Development And Differentiat

Administered By
Medicine, Cardiology
AwardedBy
National Aeronautics and Space Administration
Role
Principal Investigator
Start Date
September 01, 1995
End Date
September 18, 1997
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Publications:

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.

To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA.Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates. Groups were compared using mixed models. Bivariate associations were assessed with Spearman correlation.Compared to controls, patients with RA had 75% greater muscle concentrations of IL-6 protein (p = 0.006). In patients with RA, muscle concentrations of inflammatory markers were positively associated (p < 0.05 for all) with disease activity (IL-1β, IL-8), disability (IL-1β, IL-6), pain (IL-1β, TNF-α, toll-like receptor (TLR)-4), and physical inactivity (IL-1β, IL-6). Muscle cytokines were not related to corresponding systemic cytokines. Prominent among the gene sets differentially expressed in muscles in RA versus controls were those involved in skeletal muscle repair processes and glycolytic metabolism. Metabolic profiling revealed 46% higher concentrations of pyruvate in muscle in RA (p < 0.05), and strong positive correlation between levels of amino acids involved in fibrosis (arginine, ornithine, proline, and glycine) and disability (p < 0.05).RA is accompanied by broad-ranging molecular alterations in skeletal muscle. Analysis of inflammatory markers, gene expression, and metabolic intermediates linked disease-related disruptions in muscle inflammatory signaling, remodeling, and metabolic programming to physical inactivity and disability. Thus, skeletal muscle dysfunction might contribute to a viscous cycle of RA disease activity, physical inactivity, and disability.

Authors
Huffman, KM; Jessee, R; Andonian, B; Davis, BN; Narowski, R; Huebner, JL; Kraus, VB; McCracken, J; Gilmore, BF; Tune, KN; Campbell, M; Koves, TR; Muoio, DM; Hubal, MJ; Kraus, WE
MLA Citation
Huffman, KM, Jessee, R, Andonian, B, Davis, BN, Narowski, R, Huebner, JL, Kraus, VB, McCracken, J, Gilmore, BF, Tune, KN, Campbell, M, Koves, TR, Muoio, DM, Hubal, MJ, and Kraus, WE. "Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability." Arthritis research & therapy 19.1 (January 23, 2017): 12-.
Website
http://hdl.handle.net/10161/13703
PMID
28114971
Source
epmc
Published In
Arthritis Research and Therapy
Volume
19
Issue
1
Publish Date
2017
Start Page
12
DOI
10.1186/s13075-016-1215-7

A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses with Mortality.

Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of GlycA-a novel serum inflammatory biomarker that is an aggregate measure of enzymatically glycosylated acute phase proteins-and HDL subclasses on adverse events in a retrospective observational study of a secondary prevention population and to understand a priori defined potential interactions between GlycA and HDL subclasses.GlycA and HDL subclasses were measured using proton nuclear magnetic resonance spectroscopy in 7617 individuals in the CATHGEN (CATHeterization GENetics) cardiac catheterization biorepository.GlycA was associated with presence [odds ratio (OR) 1.07 (1.02-1.13), P = 0.01] and extent [OR 1.08 (1.03, 1.12) P < 0.0005] of coronary artery disease and with all-cause mortality [hazard ratio (HR) 1.34 (1.29-1.39), P < 0.0001], cardiovascular mortality [1.37 (1.30-1.45), P < 0.0001] and noncardiovascular mortality [1.46 (1.39-1.54) P < 0.0001] in models adjusted for 10 cardiovascular risk factors. GlycA and smaller HDL subclasses had independent but opposite effects on mortality risk prediction, with smaller HDL subclasses being protective [HR 0.69 (0.66-0.72), P < 0.0001]. There was an interaction between GlycA and smaller HDL subclasses-increasing GlycA concentrations attenuated the inverse association of smaller HDL subclasses with mortality. Adding GlycA and smaller HDL subclasses into the GRACE (Global Registry of Acute Coronary Events) and Framingham Heart Study Risk Scores improved mortality risk prediction, discrimination and reclassification.These findings highlight the interaction of systemic inflammation and HDL with clinical outcomes and may increase precision for clinical risk assessment in secondary prevention populations.

Authors
McGarrah, RW; Kelly, JP; Craig, DM; Haynes, C; Jessee, RC; Huffman, KM; Kraus, WE; Shah, SH
MLA Citation
McGarrah, RW, Kelly, JP, Craig, DM, Haynes, C, Jessee, RC, Huffman, KM, Kraus, WE, and Shah, SH. "A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses with Mortality." Clinical chemistry 63.1 (January 2017): 288-296.
PMID
27811210
Source
epmc
Published In
Clinical chemistry
Volume
63
Issue
1
Publish Date
2017
Start Page
288
End Page
296
DOI
10.1373/clinchem.2016.261636

Socioeconomic and partner status in chronic heart failure: Relationship to exercise capacity, quality of life, and clinical outcomes.

Prognosis in patients with heart failure (HF) is commonly assessed based on clinical characteristics. The association between partner status and socioeconomic status (SES) and outcomes in chronic HF requires further study.We performed a post hoc analysis of HF-ACTION, which randomized 2,331 HF patients with ejection fraction ≤35% to usual care ± aerobic exercise training. We examined baseline quality of life and functional capacity and outcomes (all-cause mortality/hospitalization) by partner status and SES using adjusted Cox models and explored an interaction with exercise training. Outcomes were examined based on partner status, education level, annual income, and employment.Having a partner, education beyond high school, an income >$25,000, and being employed were associated with better baseline functional capacity and quality of life. Over a median follow-up of 2.5 years, higher education, higher income, being employed, and having a partner were associated with lower all-cause mortality/hospitalization. After multivariable adjustment, lower mortality was seen associated with having a partner (hazard ratio 0.91, 95% CI 0.81-1.03, P=.15) and more than a high school education (hazard ratio 0.91, CI 0.80-1.02, P=.12), although these associations were not statistically significant. There was no interaction between any of these variables and exercise training on outcomes (all P>.5).Having a partner and higher SES were associated with greater functional capacity and quality of life at baseline but were not independent predictors of long-term clinical outcomes in patients with chronic HF. These findings provide information that may be considered as potential variables impacting outcomes.

Authors
Verma, AK; Schulte, PJ; Bittner, V; Keteyian, SJ; Fleg, JL; Piña, IL; Swank, AM; Fitz-Gerald, M; Ellis, SJ; Kraus, WE; Whellan, DJ; O'Connor, CM; Mentz, RJ
MLA Citation
Verma, AK, Schulte, PJ, Bittner, V, Keteyian, SJ, Fleg, JL, Piña, IL, Swank, AM, Fitz-Gerald, M, Ellis, SJ, Kraus, WE, Whellan, DJ, O'Connor, CM, and Mentz, RJ. "Socioeconomic and partner status in chronic heart failure: Relationship to exercise capacity, quality of life, and clinical outcomes." American heart journal 183 (January 2017): 54-61.
PMID
27979042
Source
epmc
Published In
American Heart Journal
Volume
183
Publish Date
2017
Start Page
54
End Page
61
DOI
10.1016/j.ahj.2016.10.007

Aerobic exercise training and general health status in ambulatory heart failure patients with a reduced ejection fraction—Findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)trial

Authors
Ambrosy, AP; Cerbin, LP; DeVore, AD; Greene, SJ; Kraus, WE; O'Connor, CM; Piña, IL; Whellan, DJ; Wojdyla, D; Wu, A; Mentz, RJ
MLA Citation
Ambrosy, AP, Cerbin, LP, DeVore, AD, Greene, SJ, Kraus, WE, O'Connor, CM, Piña, IL, Whellan, DJ, Wojdyla, D, Wu, A, and Mentz, RJ. "Aerobic exercise training and general health status in ambulatory heart failure patients with a reduced ejection fraction—Findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)trial." American Heart Journal (January 2017).
Source
crossref
Published In
American Heart Journal
Publish Date
2017
DOI
10.1016/j.ahj.2016.12.017

Apolipoprotein L1 Genetic Variants Are Associated with Chronic Kidney Disease but Not with Cardiovascular Disease in a Population Referred for Cardiac Catheterization

Authors
Wang, H; Pun, PH; Kwee, L; Craig, D; Haynes, C; Chryst-Ladd, M; Svetkey, LP; Patel, UD; Hauser, ER; Pollak, MR; Kraus, WE; Shah, SH
MLA Citation
Wang, H, Pun, PH, Kwee, L, Craig, D, Haynes, C, Chryst-Ladd, M, Svetkey, LP, Patel, UD, Hauser, ER, Pollak, MR, Kraus, WE, and Shah, SH. "Apolipoprotein L1 Genetic Variants Are Associated with Chronic Kidney Disease but Not with Cardiovascular Disease in a Population Referred for Cardiac Catheterization." Cardiorenal Medicine (2017): 96-103.
Source
crossref
Published In
CardioRenal Medicine
Publish Date
2017
Start Page
96
End Page
103
DOI
10.1159/000453458

Application of the Marginal Structural Model to Account for Suboptimal Adherence in a Randomized Controlled Trial.

BACKGROUND: There is considerable interest in adjusting for suboptimal adherence in randomized controlled trials. A per-protocol analysis, for example removes individuals who fail to achieve a minimal level of adherence. One can also reassign non-adherers to the control group, censor them at the point of non-adherence, or cross them over to the control. However, there are biases inherent in each of these methods. Here, we describe an application of causal modeling to address this issue. METHODS: The marginal structural model with inverse-probability weighting was implemented using a weighted generalized estimating equation model. Two ancillary models were developed to derive the weights. First, stepwise linear regression was used to model the observed percent weight loss, while stepwise logistic regression model was applied to model early discontinuation from the intervention. From these, participant- and time-specific weights were calculated. DISCUSSION: This model is complicated and requires careful attention to detail. Which variables to force into the ancillary models, how to construct interaction terms, and how to address time-dependent covariates must be considered. Nevertheless, it can be used to great effect to predict intervention effects at full adherence. Moreover, by contrasting these results against intention-to-treat results, insights can be gained into the intrinsic physiologic effect of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00427193.

Authors
Rochon, J; Bhapkar, M; Pieper, CF; Kraus, WE
MLA Citation
Rochon, J, Bhapkar, M, Pieper, CF, and Kraus, WE. "Application of the Marginal Structural Model to Account for Suboptimal Adherence in a Randomized Controlled Trial." Contemp Clin Trials Commun 4 (December 15, 2016): 222-228.
PMID
27900372
Source
pubmed
Published In
Contemp Clin Trials Commun
Volume
4
Publish Date
2016
Start Page
222
End Page
228
DOI
10.1016/j.conctc.2016.10.005

Associations among plasma metabolite levels and short-term exposure to PM2.5 and ozone in a cardiac catheterization cohort.

Exposure to ambient particulate matter (PM) and ozone has been associated with cardiovascular disease (CVD). However, the mechanisms linking PM and ozone exposure to CVD remain poorly understood.This study explored associations between short-term exposures to PM with a diameter <2.5μm (PM2.5) and ozone with plasma metabolite concentrations.We used cross-sectional data from a cardiac catheterization cohort at Duke University, North Carolina (NC), USA, accumulated between 2001 and 2007. Amino acids, acylcarnitines, ketones and total non-esterified fatty acid plasma concentrations were determined in fasting samples. Daily concentrations of PM2.5 and ozone were obtained from a Bayesian space-time hierarchical model, matched to each patient's residential address. Ten metabolites were selected for the analysis based on quality criteria and cluster analysis. Associations between metabolites and PM2.5 or ozone were analyzed using linear regression models adjusting for long-term trend and seasonality, calendar effects, meteorological parameters, and participant characteristics. We found delayed associations between PM2.5 or ozone and changes in metabolite levels of the glycine-ornithine-arginine metabolic axis and incomplete fatty acid oxidation associated with mitochondrial dysfunction. The strongest association was seen for an increase of 8.1μg/m3 in PM2.5 with a lag of one day and decreased mean glycine concentrations (-2.5% [95% confidence interval: -3.8%; -1.2%]).Short-term exposures to ambient PM2.5 and ozone is associated with changes in plasma concentrations of metabolites in a cohort of cardiac catheterization patients. Our findings might help to understand the link between air pollution and cardiovascular disease.

Authors
Breitner, S; Schneider, A; Devlin, RB; Ward-Caviness, CK; Diaz-Sanchez, D; Neas, LM; Cascio, WE; Peters, A; Hauser, ER; Shah, SH; Kraus, WE
MLA Citation
Breitner, S, Schneider, A, Devlin, RB, Ward-Caviness, CK, Diaz-Sanchez, D, Neas, LM, Cascio, WE, Peters, A, Hauser, ER, Shah, SH, and Kraus, WE. "Associations among plasma metabolite levels and short-term exposure to PM2.5 and ozone in a cardiac catheterization cohort." Environment international 97 (December 2016): 76-84.
PMID
27792908
Source
epmc
Published In
Environment International
Volume
97
Publish Date
2016
Start Page
76
End Page
84
DOI
10.1016/j.envint.2016.10.012

The Effect of Vigorous- Versus Moderate-Intensity Aerobic Exercise on Insulin Action.

Due to the beneficial effects on a wide range of modern medical conditions, most professional societies recommend regular aerobic exercise as part of a healthy lifestyle. Many of the exercise-related health benefits exhibit a dose-response relationship: Up to a point, more exercise is more beneficial. However, recent studies have suggested that different exercise intensities may provide distinct health benefits, independent of energy expenditure (i.e., exercise dose). One of these benefits, primarily mediated by the skeletal muscle, is exercise-related changes in insulin action and glucose homeostasis. Glucose uptake in the exercising muscle occurs through insulin-independent mechanisms whose downstream signaling events ultimately converge with insulin-signaling pathways, a fact that may explain why exercise and insulin have additive effect on skeletal muscle glucose uptake. Although the existing evidence is somewhat conflicting, well-controlled randomized studies suggest that, when controlled for total energy expenditure, moderate-intensity aerobic exercise improves insulin sensitivity more than vigorous-intensity aerobic exercise. The mechanisms underlying this difference are largely unknown. One possible explanation involves enhanced metabolism of fatty acid stores in the skeletal muscle by moderate-intensity exercise, which may directly improve insulin sensitivity. Overall, new technologic and physiologic investigative tools are beginning to shed light on the biology. Further understanding of these mechanisms will lead to better understanding of the clinical implications of a healthy lifestyle and may ultimately offer new therapeutic targets for common medical conditions such as insulin resistance and diabetes.

Authors
McGarrah, RW; Slentz, CA; Kraus, WE
MLA Citation
McGarrah, RW, Slentz, CA, and Kraus, WE. "The Effect of Vigorous- Versus Moderate-Intensity Aerobic Exercise on Insulin Action." Current cardiology reports 18.12 (December 2016): 117-. (Review)
PMID
27796854
Source
epmc
Published In
Current Cardiology Reports
Volume
18
Issue
12
Publish Date
2016
Start Page
117

Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes.

Whole body insulin sensitivity (Si) typically improves after aerobic exercise training; however, individual responses can be highly variable. The purpose of this study was to use global gene expression to identify skeletal muscle genes that correlate with exercise-induced Si changes.Longitudinal cohorts from the Studies of Targeted Risk Reduction Intervention through Defined Exercise were used as Discovery (Affymetrix) and Confirmation (Illumina) of vastus lateralis gene expression profiles. Discovery (n = 39; 21 men) and Confirmation (n = 42; 19 men) cohorts were matched for age (52 ± 8 vs 51 ± 10 yr), body mass index (30.4 ± 2.8 vs 29.7 ± 2.8 kg·m), and V˙O2max (30.4 ± 2.8 vs 29.7 ± 2.8 mL·kg·min). Si was determined via intravenous glucose tolerance test pretraining and posttraining. Pearson product-moment correlation coefficients determined relationships between a) baseline and b) training-induced changes in gene expression and %ΔSi after training.Expression of 2454 (Discovery) and 1778 genes (Confirmation) at baseline were significantly (P < 0.05) correlated to %ΔSi; 112 genes overlapped. Pathway analyses identified Ca signaling-related transcripts in this 112-gene list. Expression changes of 1384 (Discovery) and 1288 genes (Confirmation) after training were significantly (P < 0.05) correlated to %ΔSi; 33 genes overlapped, representing contractile apparatus of skeletal and smooth muscle genes. Pyruvate dehydrogenase phosphatase regulatory subunit expression at baseline (P = 0.01, r = 0.41) and posttraining (P = 0.01, r = 0.43) were both correlated with %ΔSi.Exercise-induced adaptations in skeletal muscle Si are related to baseline levels of Ca-regulating transcripts, which may prime the muscle for adaptation. Relationships between %ΔSi and pyruvate dehydrogenase phosphatase regulatory, a regulatory subunit of the pyruvate dehydrogenase complex, indicate that the Si response is strongly related to key steps in metabolic regulation.

Authors
Barberio, MD; Huffman, KM; Giri, M; Hoffman, EP; Kraus, WE; Hubal, MJ
MLA Citation
Barberio, MD, Huffman, KM, Giri, M, Hoffman, EP, Kraus, WE, and Hubal, MJ. "Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes." Medicine and science in sports and exercise 48.12 (December 2016): 2387-2397.
PMID
27846149
Source
epmc
Published In
Medicine and Science in Sports and Exercise
Volume
48
Issue
12
Publish Date
2016
Start Page
2387
End Page
2397

Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations.

Older age and obesity are associated with metabolic dysregulation; the mechanism by which these factors impact metabolism across the lifespan is important, but relatively unknown. We evaluated a panel of amino acids (AAs) and acylcarnitines (ACs) to identify effects of age and adiposity (body mass index) on circulating small-molecule metabolites in a meta-analysis of six diverse study populations.Targeted metabolic profiling was performed in six independent studies, representing 739 subjects with a broad range of age, body mass index, health states, and ethnic origin. Principal components analysis was performed on log-normalized values for AAs and ACs separately, generating one AC factor and two AA factors for each study. A common AC factor consisted primarily of acetylcarnitine, medium-chain AC, and several long-chain AC. AA Factor 1 consisted primarily of large neutral AAs. Glycine was its own factor.Metabolic profiling and factor analysis identified clusters of related metabolites of lipid and AA metabolism that were consistently associated with age and body mass in a series of studies with a broad range of age, body mass index, and health status. An inverse association of glycine with body mass index and male gender supports its role as a marker of favorable metabolic health.An important focus of future investigations should be to determine whether these clusters of metabolic intermediates are possible early predictors of health outcomes associated with body mass; are involved with accelerated aging; are involved in the causative pathway of aging; and how modification of these metabolic pathways impact the biology of aging.

Authors
Kraus, WE; Pieper, CF; Huffman, KM; Thompson, DK; Kraus, VB; Morey, MC; Cohen, HJ; Ravussin, E; Redman, LM; Bain, JR; Stevens, RD; Newgard, CB
MLA Citation
Kraus, WE, Pieper, CF, Huffman, KM, Thompson, DK, Kraus, VB, Morey, MC, Cohen, HJ, Ravussin, E, Redman, LM, Bain, JR, Stevens, RD, and Newgard, CB. "Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations." The journals of gerontology. Series A, Biological sciences and medical sciences 71.11 (November 2016): 1507-1513.
PMID
26984390
Source
epmc
Published In
Journals of Gerontology: Series A
Volume
71
Issue
11
Publish Date
2016
Start Page
1507
End Page
1513

Short-term effects of air temperature on plasma metabolite concentrations in patients undergoing cardiac catheterization.

Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease.To investigate short-term temperature effects on metabolites related to cardiovascular disease.Concentrations of 45 acylcarnitines, 15 amino acids, ketone bodies and total free fatty acids were available in 2869 participants from the CATHeterization GENetics cohort recruited at the Duke University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten metabolites were selected based on quality criteria and cluster analysis. Daily averages of meteorological variables were obtained from the North American Regional Reanalysis project. Immediate, lagged, and cumulative temperature effects on metabolite concentrations were analyzed using (piecewise) linear regression models.Linear temperature effects were found for glycine, C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5°C increase in temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%] increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1-DC (lag of four days), and a -1.4% [-2.4%; -0.3%] decrease in aspartic acid/asparagine (lag of two days). Non-linear temperature effects were observed for alanine and total ketone bodies with breakpoint of 4°C and 20°C, respectively. Both a 5°C decrease in temperature on colder days (<4°C)and a 5°C increase in temperature on warmer days (≥4°C) were associated with a four day delayed increase in alanine by 6.6% [11.7; 1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate (0-day lag) increases of 4.2% [-0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated with 5°C decreases on colder (<20°C) days and 5°C increases on warmer days (≥20°C), respectively.We observed multiple effects of air temperature on metabolites several of which are reported to be involved in cardiovascular disease. Our findings might help to understand the link between air temperature and cardiovascular disease.

Authors
Hampel, R; Breitner, S; Kraus, WE; Hauser, E; Shah, S; Ward-Caviness, CK; Devlin, R; Diaz-Sanchez, D; Neas, L; Cascio, W; Peters, A; Schneider, A
MLA Citation
Hampel, R, Breitner, S, Kraus, WE, Hauser, E, Shah, S, Ward-Caviness, CK, Devlin, R, Diaz-Sanchez, D, Neas, L, Cascio, W, Peters, A, and Schneider, A. "Short-term effects of air temperature on plasma metabolite concentrations in patients undergoing cardiac catheterization." Environmental research 151 (November 2016): 224-232.
PMID
27500855
Source
epmc
Published In
Environmental Research
Volume
151
Publish Date
2016
Start Page
224
End Page
232
DOI
10.1016/j.envres.2016.07.010

Follow-up of GxE Interactions: EBF1 GxE Association, Synthetic Chronic Psychosocial Stress, and Dropout from a Structured Exercise Program

Authors
Singh, A; Hauser, ER; Johnson, JL; Babyak, MA; Brummett, BH; Jiang, R; Slentz, CA; Huffman, KM; Siegler, IC; Williams, RB; Kraus, WE
MLA Citation
Singh, A, Hauser, ER, Johnson, JL, Babyak, MA, Brummett, BH, Jiang, R, Slentz, CA, Huffman, KM, Siegler, IC, Williams, RB, and Kraus, WE. "Follow-up of GxE Interactions: EBF1 GxE Association, Synthetic Chronic Psychosocial Stress, and Dropout from a Structured Exercise Program." November 2016.
Source
wos-lite
Published In
Genetic Epidemiology
Volume
40
Issue
7
Publish Date
2016
Start Page
662
End Page
663

Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial.

Although the Diabetes Prevention Program (DPP) established lifestyle changes (diet, exercise and weight loss) as the 'gold standard' preventive therapy for diabetes, the relative contribution of exercise alone to the overall utility of the combined diet and exercise effect of DPP is unknown; furthermore, the optimal intensity of exercise for preventing progression to diabetes remains very controversial. To establish clinical efficacy, we undertook a study (2009 to 2013) to determine: how much of the effect on measures of glucose homeostasis of a 6 month programme modelled after the first 6 months of the DPP is due to exercise alone; whether moderate- or vigorous-intensity exercise is better for improving glucose homeostasis; and to what extent amount of exercise is a contributor to improving glucose control. The primary outcome was improvement in fasting plasma glucose, with improvement in plasma glucose AUC response to an OGTT as the major secondary outcome.The trial was a parallel clinical trial. Sedentary, non-smokers who were 45-75 year old adults (n = 237) with elevated fasting glucose (5.28-6.94 mmol/l) but without cardiovascular disease, uncontrolled hypertension, or diabetes, from the Durham area, were studied at Duke University. They were randomised into one of four 6 month interventions: (1) low amount (42 kJ kg body weight(-1) week(-1) [KKW])/moderate intensity: equivalent of expending 42 KKW (e.g. walking ∼16 km [8.6 miles] per week) with moderate-intensity (50% [Formula: see text]) exercise; (2) high amount (67 KKW)/moderate intensity: equivalent of expending 67 KKW (∼22.3 km [13.8 miles] per week) with moderate-intensity exercise; (3) high amount (67 KKW)/vigorous intensity: equivalent to group 2, but with vigorous-intensity exercise (75% [Formula: see text]); and (4) diet + 42 KKW moderate intensity: same as group 1 but with diet and weight loss (7%) to mimic the first 6 months of the DPP. Computer-generated randomisation lists were provided by our statistician (G. P. Samsa). The randomisation list was maintained by L. H. Willis and C. A. Slentz with no knowledge of or input into the scheduling, whereas all scheduling was done by L. A. Bateman, with no knowledge of the randomisation list. Subjects were automatically assigned to the next group listed on the randomisation sheet (with no ability to manipulate the list order) on the day that they came in for the OGTT, by L. H. Willis. All plasma analysis was done blinded by the individuals doing the measurements (i.e. lipids, glucose, insulin). Subjects and research staff (other than individuals analysing the blood) were not blinded to the group assignments.Number randomised, completers and number analysed with complete OGTT data for each group were: low-amount/moderate-intensity (61, 43, 35); high-amount/moderate-intensity (61, 44, 40); high-amount/vigorous-intensity (61, 43, 38); diet/exercise (54, 45, 37), respectively. Only the diet and exercise group experienced a decrease in fasting glucose (p < 0.001). The means and 95% CIs for changes in fasting glucose (mmol/l) for each group were: high-amount/moderate-intensity -0.07 (-0.20, 0.06); high-amount/vigorous 0.06 (-0.07, 0.19); low-amount/moderate 0.05 (-0.05, 0.15); and diet/exercise -0.32 (-0.46, -0.18). The effects sizes for each group (in the same order) were: 0.17, 0.15, 0.18 and 0.71, respecively. For glucose tolerance (glucose AUC of OGTT), similar improvements were observed for the diet and exercise (8.2% improvement, effect size 0.73) and the 67 KKW moderate-intensity exercise (6.4% improvement, effect size 0.60) groups; moderate-intensity exercise was significantly more effective than the same amount of vigorous-intensity exercise (p < 0.0207). The equivalent amount of vigorous-intensity exercise alone did not significantly improve glucose tolerance (1.2% improvement, effect size 0.21). Changes in insulin AUC, fasting plasma glucose and insulin did not differ among the exercise groups and were numerically inferior to the diet and exercise group.In the present clinical efficacy trial we found that a high amount of moderate-intensity exercise alone was very effective at improving oral glucose tolerance despite a relatively modest 2 kg change in body fat mass. These data, combined with numerous published observations of the strong independent relation between postprandial glucose concentrations and prediction of future diabetes, suggest that walking ∼18.2 km (22.3 km prescribed with 81.6% adherence in the 67 KKW moderate-intensity group) per week may be nearly as effective as a more intensive multicomponent approach involving diet, exercise and weight loss for preventing the progression to diabetes in prediabetic individuals. These findings have important implications for the choice of clinical intervention to prevent progression to type 2 diabetes for those at high risk.ClinicalTrials.gov NCT00962962 FUNDING: The study was funded by National Institutes for Health National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NDDK) (R01DK081559).

Authors
Slentz, CA; Bateman, LA; Willis, LH; Granville, EO; Piner, LW; Samsa, GP; Setji, TL; Muehlbauer, MJ; Huffman, KM; Bales, CW; Kraus, WE
MLA Citation
Slentz, CA, Bateman, LA, Willis, LH, Granville, EO, Piner, LW, Samsa, GP, Setji, TL, Muehlbauer, MJ, Huffman, KM, Bales, CW, and Kraus, WE. "Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial." Diabetologia 59.10 (October 2016): 2088-2098.
PMID
27421729
Source
epmc
Published In
Diabetologia
Volume
59
Issue
10
Publish Date
2016
Start Page
2088
End Page
2098
DOI
10.1007/s00125-016-4051-z

Relation of Angina Pectoris to Outcomes, Quality of Life, and Response to Exercise Training in Patients With Chronic Heart Failure (from HF-ACTION).

Angina pectoris (AP) is associated with worse outcomes in heart failure (HF). We investigated the association of AP with health-related quality of life (HRQoL), exercise capacity, and clinical outcomes and its interaction with exercise training in an HF population. We grouped 2,331 patients with HF with reduced ejection fraction in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial of usual care ± exercise training according to whether they had self-reported AP by Canadian classification score. HRQoL and clinical outcomes were assessed by AP status. In HF-ACTION, 406 patients (17%) had AP at baseline (44% with Canadian classification score ≥II) with HF severity similar to those without AP. Patients with AP had similar baseline exercise capacity but worse depressive symptoms and HRQoL. AP was associated with 22% greater adjusted risk for all-cause mortality/hospitalizations, driven by hospitalizations. There was significant interaction between baseline AP and exercise training peak VO2 change (p = 0.019) but not other end points. Exercise training was associated with greater peak VO2 improvement after 3 months in patients with AP (treatment effect = 1.25 ml/kg/min, 95% CI 0.6 to 1.9). In conclusion, AP was associated with worse HRQoL and depressive symptoms. Despite greater peak VO2 improvement with exercise training, patients with AP experienced more adverse outcomes.

Authors
Parikh, KS; Coles, A; Schulte, PJ; Kraus, WE; Fleg, JL; Keteyian, SJ; Piña, IL; Fiuzat, M; Whellan, DJ; O'Connor, CM; Mentz, RJ
MLA Citation
Parikh, KS, Coles, A, Schulte, PJ, Kraus, WE, Fleg, JL, Keteyian, SJ, Piña, IL, Fiuzat, M, Whellan, DJ, O'Connor, CM, and Mentz, RJ. "Relation of Angina Pectoris to Outcomes, Quality of Life, and Response to Exercise Training in Patients With Chronic Heart Failure (from HF-ACTION)." The American journal of cardiology 118.8 (October 2016): 1211-1216.
PMID
27561194
Source
epmc
Published In
The American Journal of Cardiology
Volume
118
Issue
8
Publish Date
2016
Start Page
1211
End Page
1216
DOI
10.1016/j.amjcard.2016.07.040

Medical Training to Achieve Competency in Lifestyle Counseling: An Essential Foundation for Prevention and Treatment of Cardiovascular Diseases and Other Chronic Medical Conditions: A Scientific Statement From the American Heart Association.

Authors
Hivert, M-F; Arena, R; Forman, DE; Kris-Etherton, PM; McBride, PE; Pate, RR; Spring, B; Trilk, J; Van Horn, LV; Kraus, WE
MLA Citation
Hivert, M-F, Arena, R, Forman, DE, Kris-Etherton, PM, McBride, PE, Pate, RR, Spring, B, Trilk, J, Van Horn, LV, and Kraus, WE. "Medical Training to Achieve Competency in Lifestyle Counseling: An Essential Foundation for Prevention and Treatment of Cardiovascular Diseases and Other Chronic Medical Conditions: A Scientific Statement From the American Heart Association." Circulation 134.15 (October 2016): e308-e327.
PMID
27601568
Source
epmc
Published In
Circulation
Volume
134
Issue
15
Publish Date
2016
Start Page
e308
End Page
e327

A novel approach for measuring residential socioeconomic factors associated with cardiovascular and metabolic health.

Individual-level characteristics, including socioeconomic status, have been associated with poor metabolic and cardiovascular health; however, residential area-level characteristics may also independently contribute to health status. In the current study, we used hierarchical clustering to aggregate 444 US Census block groups in Durham, Orange, and Wake Counties, NC, USA into six homogeneous clusters of similar characteristics based on 12 demographic factors. We assigned 2254 cardiac catheterization patients to these clusters based on residence at first catheterization. After controlling for individual age, sex, smoking status, and race, there were elevated odds of patients being obese (odds ratio (OR)=1.92, 95% confidence intervals (CI)=1.39, 2.67), and having diabetes (OR=2.19, 95% CI=1.57, 3.04), congestive heart failure (OR=1.99, 95% CI=1.39, 2.83), and hypertension (OR=2.05, 95% CI=1.38, 3.11) in a cluster that was urban, impoverished, and unemployed, compared with a cluster that was urban with a low percentage of people that were impoverished or unemployed. Our findings demonstrate the feasibility of applying hierarchical clustering to an assessment of area-level characteristics and that living in impoverished, urban residential clusters may have an adverse impact on health.Journal of Exposure Science and Environmental Epidemiology advance online publication, 21 September 2016; doi:10.1038/jes.2016.53.

Authors
Mirowsky, JE; Devlin, RB; Diaz-Sanchez, D; Cascio, W; Grabich, SC; Haynes, C; Blach, C; Hauser, ER; Shah, S; Kraus, W; Olden, K; Neas, L
MLA Citation
Mirowsky, JE, Devlin, RB, Diaz-Sanchez, D, Cascio, W, Grabich, SC, Haynes, C, Blach, C, Hauser, ER, Shah, S, Kraus, W, Olden, K, and Neas, L. "A novel approach for measuring residential socioeconomic factors associated with cardiovascular and metabolic health." Journal of exposure science & environmental epidemiology (September 21, 2016).
PMID
27649842
Source
epmc
Published In
Journal of Exposure Science and Environmental Epidemiology
Publish Date
2016
DOI
10.1038/jes.2016.53

Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION.

The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response.Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF).HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity (peak oxygen consumption and 6-min walk distance) from baseline to 3 months. We also assessed for a treatment interaction among atorvastatin, simvastatin, and pravastatin and change in these endpoints with ET. Multiple linear regression analyses were performed for each endpoint, adjusting for baseline covariates.Of 2,331 patients in the HF-ACTION trial, 1,353 (58%) were prescribed statins at baseline. Patients treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers. There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity, nor was there evidence of differential association between statin type and ET response for these endpoints (all p values >0.05).In a large chronic HF cohort, there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET. These findings contrast with recent reports of an attenuation in ET response with statins in a different population, highlighting the need for future prospective studies. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Authors
Kelly, JP; Dunning, A; Schulte, PJ; Fiuzat, M; Leifer, ES; Fleg, JL; Cooper, LS; Keteyian, SJ; Kitzman, DW; Pina, IL; Kraus, WE; Whellan, DJ; O'Connor, CM; Mentz, RJ
MLA Citation
Kelly, JP, Dunning, A, Schulte, PJ, Fiuzat, M, Leifer, ES, Fleg, JL, Cooper, LS, Keteyian, SJ, Kitzman, DW, Pina, IL, Kraus, WE, Whellan, DJ, O'Connor, CM, and Mentz, RJ. "Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION." JACC. Heart failure 4.8 (August 2016): 617-624.
PMID
27395348
Source
epmc
Published In
JACC: Heart Failure
Volume
4
Issue
8
Publish Date
2016
Start Page
617
End Page
624
DOI
10.1016/j.jchf.2016.05.006

Exercise Training in Patients with Chronic Heart Failure and Atrial Fibrillation: Results from the HF-ACTION Trial

Authors
Luo, N; Merrill, P; Whellan, DJ; Pina, IL; Fiuzat, M; Kraus, WE; Kitzman, DW; Keteyian, SJ; O'Connor, CM; Mentz, RJ
MLA Citation
Luo, N, Merrill, P, Whellan, DJ, Pina, IL, Fiuzat, M, Kraus, WE, Kitzman, DW, Keteyian, SJ, O'Connor, CM, and Mentz, RJ. "Exercise Training in Patients with Chronic Heart Failure and Atrial Fibrillation: Results from the HF-ACTION Trial." August 2016.
Source
wos-lite
Published In
Journal of Cardiac Failure
Volume
22
Issue
8
Publish Date
2016
Start Page
S71
End Page
S71

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.

Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No-HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long-chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no-HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

Authors
Hunter, WG; Kelly, JP; McGarrah, RW; Khouri, MG; Craig, D; Haynes, C; Ilkayeva, O; Stevens, RD; Bain, JR; Muehlbauer, MJ; Newgard, CB; Felker, GM; Hernandez, AF; Velazquez, EJ; Kraus, WE; Shah, SH
MLA Citation
Hunter, WG, Kelly, JP, McGarrah, RW, Khouri, MG, Craig, D, Haynes, C, Ilkayeva, O, Stevens, RD, Bain, JR, Muehlbauer, MJ, Newgard, CB, Felker, GM, Hernandez, AF, Velazquez, EJ, Kraus, WE, and Shah, SH. "Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure." Journal of the American Heart Association 5.8 (July 29, 2016).
Website
http://hdl.handle.net/10161/13018
PMID
27473038
Source
epmc
Published In
Journal of the American Heart Association
Volume
5
Issue
8
Publish Date
2016
DOI
10.1161/jaha.115.003190

PDPR Gene Expression Correlates with Exercise-Training Insulin Sensitivity Changes.

Whole body insulin sensitivity (Si) typically improves following aerobic exercise training; however, individual responses can be highly variable. The purpose of this study was to use global gene expression to identify skeletal muscle genes that correlate with exercise-induced Si changes.Longitudinal cohorts from the Studies of Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) were utilized as Discovery (Affymetrix) and Confirmation (Illumina) of vastus lateralis gene expression profiles. Discovery (n=39; 21 men) and Confirmation (n=42; 19 men) cohorts were matched for age (52 ± 8 vs. 51 ± 10 yr), BMI (30.4 ± 2.8 vs. 29.7 ± 2.8 kg*m), and VO2max (30.4 ± 2.8 vs. 29.7 ± 2.8 mL/kg/min). Si was determined via intravenous glucose tolerance test pre- and post-training. Pearson product-moment correlation coefficients determined relationships between a) baseline and b) training-induced changes in gene expression and %ΔSi after training.Expression of 2454 (Discovery) and 1778 genes (Confirmation) at baseline were significantly (P<0.05) correlated to %ΔSi; 112 genes overlapped. Pathway analyses identified Ca-signaling-related transcripts in this 112-gene list. Expression changes of 1384 (Discovery) and 1288 genes (Confirmation) following training were significantly (P<0.05) correlated to %ΔSi; 33 genes overlapped, representing contractile apparatus of skeletal and smooth muscle genes. Pyruvate dehydrogenase phosphatase regulatory subunit (PDPR) expression at baseline (p=0.01, r=0.41) and post-training (p=0.01, r=0.43) were both correlated with %ΔSi.Exercise-induced adaptations in skeletal muscle Si are related to baseline levels of Ca-regulating transcripts, which may prime the muscle for adaptation. Relationships between %ΔSi and PDPR, a regulatory subunit of the pyruvate dehydrogenase complex, indicate that the Si response is strongly related to key steps in metabolic regulation.

Authors
Barberio, MD; Huffman, KM; Giri, M; Hoffman, EP; Kraus, WE; Hubal, MJ
MLA Citation
Barberio, MD, Huffman, KM, Giri, M, Hoffman, EP, Kraus, WE, and Hubal, MJ. "PDPR Gene Expression Correlates with Exercise-Training Insulin Sensitivity Changes." Medicine and science in sports and exercise (July 18, 2016).
PMID
27434087
Source
epmc
Published In
Medicine and Science in Sports and Exercise
Publish Date
2016

Response to Exercise Training and Outcomes in Patients With Heart Failure and Diabetes Mellitus: Insights From the HF-ACTION Trial.

In HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), exercise training improved functional capacity in heart failure with reduced ejection fraction (HFrEF). Previous studies have suggested that diabetes mellitus (DM) may be associated with an attenuated response to exercise. We explored whether DM attenuated the improvement in functional capacity with exercise.HF-ACTION randomized 2331 patients with HFrEF to medical therapy with or without exercise training over a median follow-up of 2.5 years. We examined the interaction between DM and exercise response measured by change in 6-minute walk distance (6MWD) and peak VO2. We also examined outcomes by DM status. In HF-ACTION, 748 (32%) patients had DM. DM patients had lower functional capacity at baseline and had lower exercise volumes at 3 months. There was a significant interaction between DM status and exercise training for change in peak VO2 (interaction P = .02), but not 6MWD. In the exercise arm, DM patients had a smaller mean increase in peak VO2 than non-DM patients (P = .03). There was no interaction between DM and exercise on clinical outcomes. After risk adjustment, DM was associated with increased all-cause mortality/hospitalization (P = .03).In HF-ACTION, DM was associated with lower baseline functional capacity, an attenuated improvement in peak VO2, and increased hospitalizations.

Authors
Banks, AZ; Mentz, RJ; Stebbins, A; Mikus, CR; Schulte, PJ; Fleg, JL; Cooper, LS; Leifer, ES; Badenhop, DT; Keteyian, SJ; Piña, IL; Kitzman, DW; Fiuzat, M; Whellan, DJ; Kraus, WE; O'Connor, CM
MLA Citation
Banks, AZ, Mentz, RJ, Stebbins, A, Mikus, CR, Schulte, PJ, Fleg, JL, Cooper, LS, Leifer, ES, Badenhop, DT, Keteyian, SJ, Piña, IL, Kitzman, DW, Fiuzat, M, Whellan, DJ, Kraus, WE, and O'Connor, CM. "Response to Exercise Training and Outcomes in Patients With Heart Failure and Diabetes Mellitus: Insights From the HF-ACTION Trial." Journal of cardiac failure 22.7 (July 2016): 485-491.
PMID
26687984
Source
epmc
Published In
Journal of Cardiac Failure
Volume
22
Issue
7
Publish Date
2016
Start Page
485
End Page
491
DOI
10.1016/j.cardfail.2015.12.007

Physical Performance Across the Adult Life Span: Correlates With Age and Physical Activity.

A number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span.The physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014.Physical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function.These results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline.

Authors
Hall, KS; Cohen, HJ; Pieper, CF; Fillenbaum, GG; Kraus, WE; Huffman, KM; Cornish, MA; Shiloh, A; Flynn, C; Sloane, R; Newby, LK; Morey, MC
MLA Citation
Hall, KS, Cohen, HJ, Pieper, CF, Fillenbaum, GG, Kraus, WE, Huffman, KM, Cornish, MA, Shiloh, A, Flynn, C, Sloane, R, Newby, LK, and Morey, MC. "Physical Performance Across the Adult Life Span: Correlates With Age and Physical Activity." The journals of gerontology. Series A, Biological sciences and medical sciences (June 29, 2016).
PMID
27356977
Source
epmc
Published In
Journals of Gerontology: Series A
Publish Date
2016

Erratum: A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity (Journals of Gerontology - Series A Biological Sciences and Medical Sciences 70:9)

Authors
Ravussin, E; Redman, LM; Rochon, J; Das, SK; Fontana, L; Kraus, WE; Romashkan, S; Williamson, DA; Meydani, SN; Villareal, DT; Smith, SR; Stein, RI; Scott, TM; Stewart, TM; Saltzman, E; Klein, S; Bhapkar, M; Martin, CK; Gilhooly, CH; Holloszy, JO; Hadley, EC; Roberts, SB
MLA Citation
Ravussin, E, Redman, LM, Rochon, J, Das, SK, Fontana, L, Kraus, WE, Romashkan, S, Williamson, DA, Meydani, SN, Villareal, DT, Smith, SR, Stein, RI, Scott, TM, Stewart, TM, Saltzman, E, Klein, S, Bhapkar, M, Martin, CK, Gilhooly, CH, Holloszy, JO, Hadley, EC, and Roberts, SB. "Erratum: A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity (Journals of Gerontology - Series A Biological Sciences and Medical Sciences 70:9)." Journals of Gerontology - Series A Biological Sciences and Medical Sciences 71.6 (June 8, 2016): 839-840.
Source
scopus
Published In
Journals of Gerontology: Series A
Volume
71
Issue
6
Publish Date
2016
Start Page
839
End Page
840
DOI
10.1093/gerona/glw056

Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial.

Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety.The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70%-85% VO2peak), escitalopram (5-20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life.The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients.

Authors
Blumenthal, JA; Feger, BJ; Smith, PJ; Watkins, LL; Jiang, W; Davidson, J; Hoffman, BM; Ashworth, M; Mabe, SK; Babyak, MA; Kraus, WE; Hinderliter, A; Sherwood, A
MLA Citation
Blumenthal, JA, Feger, BJ, Smith, PJ, Watkins, LL, Jiang, W, Davidson, J, Hoffman, BM, Ashworth, M, Mabe, SK, Babyak, MA, Kraus, WE, Hinderliter, A, and Sherwood, A. "Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial." American heart journal 176 (June 2016): 53-62.
PMID
27264220
Source
epmc
Published In
American Heart Journal
Volume
176
Publish Date
2016
Start Page
53
End Page
62
DOI
10.1016/j.ahj.2016.03.003

Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease.

Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease.We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability.We found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P=1.0×10(-16)), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P=4.0×10(-6)). In a larger set of sequenced samples from Icelanders, we found another loss-of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P=1.8×10(-3)).ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.).

Authors
Nioi, P; Sigurdsson, A; Thorleifsson, G; Helgason, H; Agustsdottir, AB; Norddahl, GL; Helgadottir, A; Magnusdottir, A; Jonasdottir, A; Gretarsdottir, S; Jonsdottir, I; Steinthorsdottir, V; Rafnar, T; Swinkels, DW; Galesloot, TE; Grarup, N; Jørgensen, T; Vestergaard, H; Hansen, T; Lauritzen, T; Linneberg, A; Friedrich, N; Krarup, NT; Fenger, M; Abildgaard, U; Hansen, PR; Galløe, AM; Braund, PS; Nelson, CP; Hall, AS; Williams, MJA; van Rij, AM; Jones, GT; Patel, RS; Levey, AI; Hayek, S; Shah, SH et al.
MLA Citation
Nioi, P, Sigurdsson, A, Thorleifsson, G, Helgason, H, Agustsdottir, AB, Norddahl, GL, Helgadottir, A, Magnusdottir, A, Jonasdottir, A, Gretarsdottir, S, Jonsdottir, I, Steinthorsdottir, V, Rafnar, T, Swinkels, DW, Galesloot, TE, Grarup, N, Jørgensen, T, Vestergaard, H, Hansen, T, Lauritzen, T, Linneberg, A, Friedrich, N, Krarup, NT, Fenger, M, Abildgaard, U, Hansen, PR, Galløe, AM, Braund, PS, Nelson, CP, Hall, AS, Williams, MJA, van Rij, AM, Jones, GT, Patel, RS, Levey, AI, Hayek, S, and Shah, SH et al. "Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease." The New England journal of medicine 374.22 (June 2016): 2131-2141.
PMID
27192541
Source
epmc
Published In
The New England journal of medicine
Volume
374
Issue
22
Publish Date
2016
Start Page
2131
End Page
2141
DOI
10.1056/nejmoa1508419

Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.

Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and peripheral tissues and organs. Specifically, HF-associated metabolic dysfunction includes alterations in substrate utilization, insulin resistance, defects in energy production, and imbalanced anabolic-catabolic signaling leading to cachexia. Each of these metabolic abnormalities is associated with significant morbidity and mortality in patients with HF; however, their detection and therapeutic management remains challenging. Given the difficulty in obtaining human cardiac tissue for research purposes, peripheral blood metabolomic profiling, a well-established approach for characterizing small-molecule metabolite intermediates from canonical biochemical pathways, may be a useful technology for dissecting biomarkers and mechanisms of metabolic impairment in HF. In this review, metabolic abnormalities in HF will be discussed with particular emphasis on the application of metabolomic profiling to detecting, risk stratifying, and identifying novel targets for metabolic therapy in this heterogeneous population.

Authors
Hunter, WG; Kelly, JP; McGarrah, RW; Kraus, WE; Shah, SH
MLA Citation
Hunter, WG, Kelly, JP, McGarrah, RW, Kraus, WE, and Shah, SH. "Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling." Current heart failure reports 13.3 (June 2016): 119-131. (Review)
Website
http://hdl.handle.net/10161/13019
PMID
27216948
Source
epmc
Published In
Current Heart Failure Reports
Volume
13
Issue
3
Publish Date
2016
Start Page
119
End Page
131
DOI
10.1007/s11897-016-0289-5

Diet and Exercise for Obese Patients With Heart Failure--Reply.

Authors
Kitzman, DW; Haykowsky, MJ; Kraus, W
MLA Citation
Kitzman, DW, Haykowsky, MJ, and Kraus, W. "Diet and Exercise for Obese Patients With Heart Failure--Reply." JAMA 315.23 (June 2016): 2619-2620. (Letter)
PMID
27327807
Source
epmc
Published In
JAMA : the journal of the American Medical Association
Volume
315
Issue
23
Publish Date
2016
Start Page
2619
End Page
2620
DOI
10.1001/jama.2016.2924

AEROBIC EXERCISE TRAINING AND HEALTH STATUS IN AMBULATORY HEART FAILURE PATIENTS WITH A REDUCED EJECTION FRACTION: AN ANALYSIS FROM THE HF-ACTION TRIAL

Authors
Ambrosy, AP; Cerbin, L; DeVore, A; Greene, S; Kraus, WE; O'Connor, C; Pina, I; Whellan, D; Wojdyla, D; Wu, A; Mentz, R
MLA Citation
Ambrosy, AP, Cerbin, L, DeVore, A, Greene, S, Kraus, WE, O'Connor, C, Pina, I, Whellan, D, Wojdyla, D, Wu, A, and Mentz, R. "AEROBIC EXERCISE TRAINING AND HEALTH STATUS IN AMBULATORY HEART FAILURE PATIENTS WITH A REDUCED EJECTION FRACTION: AN ANALYSIS FROM THE HF-ACTION TRIAL." April 5, 2016.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
67
Issue
13
Publish Date
2016
Start Page
1312
End Page
1312

Cell Density and Joint microRNA-133a and microRNA-696 Inhibition Enhance Differentiation and Contractile Function of Engineered Human Skeletal Muscle Tissues.

To utilize three-dimensional (3D) engineered human skeletal muscle tissue for translational studies and in vitro studies of drug toxicity, there is a need to promote differentiation and functional behavior. In this study, we identified conditions to promote contraction of engineered human skeletal muscle bundles and examined the effects of transient inhibition of microRNAs (miRs) on myogenic differentiation and function of two-dimensional (2D) and 3D cultures of human myotubes. In 2D cultures, simultaneously inhibiting both miR-133a, which promotes myoblast proliferation, and miR-696, which represses oxidative metabolism, resulted in an increase in sarcomeric α-actinin protein and the metabolic coactivator PGC-1α protein compared to transfection with a scrambled miR sequence (negative control). Although PGC-1α was elevated following joint inhibition of miRs 133a and 696, there was no difference in myosin heavy chain (MHC) protein isoforms. 3D engineered human skeletal muscle myobundles seeded with 5 × 10(6) human skeletal myoblasts (HSkM)/mL and cultured for 2 weeks after onset of differentiation consistently did not contract when stimulated electrically, whereas those seeded with myoblasts at 10 × 10(6) HSkM/mL or higher did contract. When HSkM were transfected with both anti-miRs and seeded into fibrin hydrogels and cultured for 2 weeks under static conditions, twitch and tetanic specific forces after electrical stimulation were greater than for myobundles prepared with HSkM transfected with scrambled sequences. Immunofluorescence and Western blots of 3D myobundles indicate that anti-miR-133a or anti-miR-696 treatment led to modest increases in slow MHC, but no consistent increase in fast MHC. Similar to results in 2D, only myobundles prepared with myoblasts treated with anti-miR-133a and anti-miR-696 produced an increase in PGC-1α mRNA. PGC-1α targets were differentially affected by the treatment. HIF-2α mRNA showed an expression pattern similar to that of PGC-1α mRNA, but COXII mRNA levels were not affected by the anti-miRs. Overall, joint inhibition of miR-133a and miR-696 accelerated differentiation, elevated the metabolic coactivator PGC-1α, and increased the contractile force in 3D engineered human skeletal muscle bundles.

Authors
Cheng, CS; Ran, L; Bursac, N; Kraus, WE; Truskey, GA
MLA Citation
Cheng, CS, Ran, L, Bursac, N, Kraus, WE, and Truskey, GA. "Cell Density and Joint microRNA-133a and microRNA-696 Inhibition Enhance Differentiation and Contractile Function of Engineered Human Skeletal Muscle Tissues." Tissue engineering. Part A 22.7-8 (April 2016): 573-583.
PMID
26891613
Source
epmc
Published In
Tissue Engineering, Part A
Volume
22
Issue
7-8
Publish Date
2016
Start Page
573
End Page
583
DOI
10.1089/ten.tea.2015.0359

Safety of two-year caloric restriction in non-obese healthy individuals.

The extent to which sustained caloric restriction (CR) in healthy non-obese adults is safe has not been previously investigated.Assess the safety and tolerability of sustained two-year CR intervention in healthy, non-obese adults.A multi-center, randomized controlled trial. Participants were randomized using a 2:1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored.Three participants were withdrawn from the CR intervention because of the safety concerns. No deaths and one SAE was reported by participants in the CR group. Although the difference in AE between AL and CR groups was not significant, within the CR group, the incidence of nervous system (p = 0.02), musculoskeletal (p = 0.02) and reproductive system (p = 0.002) disorders was significantly higher in the normal-weight than in the overweight participants. At months 12 and 24, bone mineral densities at the lumbar spine, total hip, and femoral neck of participants in the CR group were significantly lower than in those in the AL group.Two-years of CR at levels achieved in CALERIE was safe and well tolerated. Close monitoring for excessive bone loss and anemia is important.

Authors
Romashkan, SV; Das, SK; Villareal, DT; Ravussin, E; Redman, LM; Rochon, J; Bhapkar, M; Kraus, WE
MLA Citation
Romashkan, SV, Das, SK, Villareal, DT, Ravussin, E, Redman, LM, Rochon, J, Bhapkar, M, and Kraus, WE. "Safety of two-year caloric restriction in non-obese healthy individuals." Oncotarget 7.15 (April 2016): 19124-19133.
PMID
26992237
Source
epmc
Published In
Oncotarget
Volume
7
Issue
15
Publish Date
2016
Start Page
19124
End Page
19133
DOI
10.18632/oncotarget.8093

Association of standard clinical and laboratory variables with red blood cell distribution width.

Red blood cell distribution width (RDW) strongly predicts clinical outcomes among patients with coronary disease and heart failure. The factors underpinning this association are unknown.In 6,447 individuals enrolled in the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) Study who had undergone coronary angiography between 2001 and 2007, we used Cox proportional hazards modeling to examine the adjusted association between RDW and death, and death or myocardial infarction (MI). Multiple linear regression using the R(2) model selection method was then used to identify clinical factors associated with variation in RDW.Median follow-up was 4.2 (interquartile range 2.3-5.9) years, and the median RDW was 13.5% (interquartile range 12.9%-14.3%, clinical laboratory reference range 11.5%-14.5%). Red blood cell distribution width was independently associated with death (adjusted hazard ratio 1.13 per 1% increase in RDW, 95% CI 1.09-1.17), and death or MI (adjusted hazard ratio 1.12, 95% CI 1.08-1.16). Twenty-seven clinical characteristics and laboratory measures were assessed in the multivariable linear regression model; a final model containing 18 variables explained only 21% of the variation in RDW.Although strongly associated with death and death or MI, only one-fifth of the variation in RDW was explained by routinely assessed clinical characteristics and laboratory measures. Understanding the latent factors that explain variation in RDW may provide insight into its strong association with risk and identify novel targets to mitigate that risk.

Authors
Guimarães, PO; Sun, J-L; Kragholm, K; Shah, SH; Pieper, KS; Kraus, WE; Hauser, ER; Granger, CB; Newby, LK
MLA Citation
Guimarães, PO, Sun, J-L, Kragholm, K, Shah, SH, Pieper, KS, Kraus, WE, Hauser, ER, Granger, CB, and Newby, LK. "Association of standard clinical and laboratory variables with red blood cell distribution width." American heart journal 174 (April 2016): 22-28.
PMID
26995366
Source
epmc
Published In
American Heart Journal
Volume
174
Publish Date
2016
Start Page
22
End Page
28
DOI
10.1016/j.ahj.2016.01.001

Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized, Clinical Efficacy Trial.

Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR.One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P=0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25-0.95; P=0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27-0.71; P<0.001).CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00981253.

Authors
Blumenthal, JA; Sherwood, A; Smith, PJ; Watkins, L; Mabe, S; Kraus, WE; Ingle, K; Miller, P; Hinderliter, A
MLA Citation
Blumenthal, JA, Sherwood, A, Smith, PJ, Watkins, L, Mabe, S, Kraus, WE, Ingle, K, Miller, P, and Hinderliter, A. "Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized, Clinical Efficacy Trial." Circulation 133.14 (April 2016): 1341-1350.
PMID
27045127
Source
epmc
Published In
Circulation
Volume
133
Issue
14
Publish Date
2016
Start Page
1341
End Page
1350
DOI
10.1161/circulationaha.115.018926

A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls.

RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA.Plasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance.On average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1β, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = -0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all).GlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.

Authors
Bartlett, DB; Connelly, MA; AbouAssi, H; Bateman, LA; Tune, KN; Huebner, JL; Kraus, VB; Winegar, DA; Otvos, JD; Kraus, WE; Huffman, KM
MLA Citation
Bartlett, DB, Connelly, MA, AbouAssi, H, Bateman, LA, Tune, KN, Huebner, JL, Kraus, VB, Winegar, DA, Otvos, JD, Kraus, WE, and Huffman, KM. "A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls." Arthritis research & therapy 18 (April 2016): 86-.
Website
http://hdl.handle.net/10161/11953
PMID
27067270
Source
epmc
Published In
Arthritis Research and Therapy
Volume
18
Publish Date
2016
Start Page
86
DOI
10.1186/s13075-016-0982-5

Correction

MLA Citation
"Correction." Journal of the American College of Cardiology 67.16 (April 2016): 1979-1980.
Source
crossref
Published In
JACC - Journal of the American College of Cardiology
Volume
67
Issue
16
Publish Date
2016
Start Page
1979
End Page
1980
DOI
10.1016/j.jacc.2016.03.005

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease.

The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets.Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes.We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P=4.2×10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P=4.0×10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P=0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P=0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P=2.0×10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P=2.5×10(-7)).We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease. (Funded by the National Institutes of Health and others.).

Authors
Stitziel, NO; Stirrups, KE; Masca, NGD; Erdmann, J; Ferrario, PG; König, IR; Weeke, PE; Webb, TR; Auer, PL; Schick, UM; Lu, Y; Zhang, H; Dube, M-P; Goel, A; Farrall, M; Peloso, GM; Won, H-H; Do, R; van Iperen, E; Kanoni, S; Kruppa, J; Mahajan, A; Scott, RA; Willenberg, C; Braund, PS; van Capelleveen, JC; Doney, ASF; Donnelly, LA; Asselta, R; Merlini, PA; Duga, S; Marziliano, N; Denny, JC; Shaffer, CM; El-Mokhtari, NE; Franke, A; Gottesman, O; Heilmann, S; Hengstenberg, C; Hoffman, P; Holmen, OL et al.
MLA Citation
Stitziel, NO, Stirrups, KE, Masca, NGD, Erdmann, J, Ferrario, PG, König, IR, Weeke, PE, Webb, TR, Auer, PL, Schick, UM, Lu, Y, Zhang, H, Dube, M-P, Goel, A, Farrall, M, Peloso, GM, Won, H-H, Do, R, van Iperen, E, Kanoni, S, Kruppa, J, Mahajan, A, Scott, RA, Willenberg, C, Braund, PS, van Capelleveen, JC, Doney, ASF, Donnelly, LA, Asselta, R, Merlini, PA, Duga, S, Marziliano, N, Denny, JC, Shaffer, CM, El-Mokhtari, NE, Franke, A, Gottesman, O, Heilmann, S, Hengstenberg, C, Hoffman, P, and Holmen, OL et al. "Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease." The New England journal of medicine 374.12 (March 2, 2016): 1134-1144.
PMID
26934567
Source
epmc
Published In
The New England journal of medicine
Volume
374
Issue
12
Publish Date
2016
Start Page
1134
End Page
1144
DOI
10.1056/nejmoa1507652

Legacy Effects of STRRIDE Exercise Training Programs on Cardiometabolic Health Observed Ten Years Later

Authors
Kraus, WE; Slentz, CA; Duscha, BD; Willis, LH; Johnson, JL
MLA Citation
Kraus, WE, Slentz, CA, Duscha, BD, Willis, LH, and Johnson, JL. "Legacy Effects of STRRIDE Exercise Training Programs on Cardiometabolic Health Observed Ten Years Later." March 1, 2016.
Source
wos-lite
Published In
Circulation
Volume
133
Publish Date
2016

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort.

Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models.Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification.Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67-0.76), p = 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p = 0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification.HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL-targeted therapies in high-risk populations.

Authors
McGarrah, RW; Craig, DM; Haynes, C; Dowdy, ZE; Shah, SH; Kraus, WE
MLA Citation
McGarrah, RW, Craig, DM, Haynes, C, Dowdy, ZE, Shah, SH, and Kraus, WE. "High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort." Atherosclerosis 246 (March 2016): 229-235.
PMID
26803432
Source
epmc
Published In
Atherosclerosis
Volume
246
Publish Date
2016
Start Page
229
End Page
235
DOI
10.1016/j.atherosclerosis.2016.01.012

A Novel Analytic Technique to Measure Associations Between Circulating Biomarkers and Physical Performance Across the Adult Life Span.

Understanding associations between circulating biomarkers and physical performance across the adult life span could aid in better describing mechanistic pathways leading to disability. We hypothesized that high concentrations of circulating biomarkers would be associated with lower functioning across study populations representing the adult life span. The data were from four intervention and two observational studies with ages ranging 22-89 years. Biomarkers assayed included inflammatory, coagulation, and endothelial function markers. Physical performance was measured either by VO2peak (studies of young and middle-aged adults) or usual gait speed (studies of older adults). Partialled (by age, body mass index, race, and sex) and weighted common correlations were calculated between biomarkers and physical performance. Homogeneity of the associations was also assessed. Interleukin-6 (weighted r = -.22), tumor necrosis factor receptor 2 (weighted r = -.19), D-dimer (weighted r = -.16), tumor necrosis factor receptor 1 (weighted r = -.15), granulocyte colony-stimulating factor (weighted r = -.14), and tumor necrosis factor alpha (weighted r = -.10) were all significantly inversely correlated with physical performance (p < .05). All significant correlations were homogeneous across studies. In summary, we observed consistent inverse associations between six circulating biomarkers and objective measures of physical performance. These results suggest that these serum biomarkers may be broadly applicable for detection, trajectory, and treatment monitoring of physical function across the life span or possibly for midlife predictors of functionally deleterious conditions.

Authors
Peterson, MJ; Thompson, DK; Pieper, CF; Morey, MC; Kraus, VB; Kraus, WE; Sullivan, P; Fillenbaum, G; Cohen, HJ
MLA Citation
Peterson, MJ, Thompson, DK, Pieper, CF, Morey, MC, Kraus, VB, Kraus, WE, Sullivan, P, Fillenbaum, G, and Cohen, HJ. "A Novel Analytic Technique to Measure Associations Between Circulating Biomarkers and Physical Performance Across the Adult Life Span." The journals of gerontology. Series A, Biological sciences and medical sciences 71.2 (February 2016): 196-202.
PMID
25745025
Source
epmc
Published In
Journals of Gerontology: Series A
Volume
71
Issue
2
Publish Date
2016
Start Page
196
End Page
202
DOI
10.1093/gerona/glv007

Association between satellite-based estimates of long-term PM2.5 exposure and coronary artery disease.

Epidemiological studies have identified associations between long-term PM2.5 exposure and cardiovascular events, though most have relied on concentrations from central-site air quality monitors.We utilized a cohort of 5679 patients who had undergone cardiac catheterization at Duke University between 2002-2009 and resided in North Carolina. We used estimates of daily PM2.5 concentrations for North Carolina during the study period based on satellite derived Aerosol Optical Depth (AOD) measurements and PM2.5 concentrations from ground monitors, which were spatially resolved with a 10×10km resolution, matched to each patient's residential address and averaged for the year prior to catheterization. The Coronary Artery Disease (CAD) index was used to measure severity of CAD; scores >23 represent a hemodynamically significant coronary artery lesion in at least one major coronary vessel. Logistic regression modeled odds of having CAD or an MI with each 1μg/m(3) increase in annual average PM2.5, adjusting for sex, race, smoking status and socioeconomic status.In adjusted models, a 1μg/m(3) increase in annual average PM2.5 was associated with an 11.1% relative increase in the odds of significant CAD (95% CI: 4.0-18.6%) and a 14.2% increase in the odds of having a myocardial infarction (MI) within a year prior (95% CI: 3.7-25.8%).Satellite-based estimates of long-term PM2.5 exposure were associated with both coronary artery disease (CAD) and incidence of myocardial infarction (MI) in a cohort of cardiac catheterization patients.

Authors
McGuinn, LA; Ward-Caviness, CK; Neas, LM; Schneider, A; Diaz-Sanchez, D; Cascio, WE; Kraus, WE; Hauser, E; Dowdy, E; Haynes, C; Chudnovsky, A; Koutrakis, P; Devlin, RB
MLA Citation
McGuinn, LA, Ward-Caviness, CK, Neas, LM, Schneider, A, Diaz-Sanchez, D, Cascio, WE, Kraus, WE, Hauser, E, Dowdy, E, Haynes, C, Chudnovsky, A, Koutrakis, P, and Devlin, RB. "Association between satellite-based estimates of long-term PM2.5 exposure and coronary artery disease." Environmental research 145 (February 2016): 9-17.
PMID
26613345
Source
epmc
Published In
Environmental Research
Volume
145
Publish Date
2016
Start Page
9
End Page
17
DOI
10.1016/j.envres.2015.10.026

Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure.

Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables.The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER).Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined.Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women.Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Authors
Keteyian, SJ; Patel, M; Kraus, WE; Brawner, CA; McConnell, TR; Piña, IL; Leifer, ES; Fleg, JL; Blackburn, G; Fonarow, GC; Chase, PJ; Piner, L; Vest, M; O'Connor, CM; Ehrman, JK; Walsh, MN; Ewald, G; Bensimhon, D; Russell, SD
MLA Citation
Keteyian, SJ, Patel, M, Kraus, WE, Brawner, CA, McConnell, TR, Piña, IL, Leifer, ES, Fleg, JL, Blackburn, G, Fonarow, GC, Chase, PJ, Piner, L, Vest, M, O'Connor, CM, Ehrman, JK, Walsh, MN, Ewald, G, Bensimhon, D, and Russell, SD. "Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure." Journal of the American College of Cardiology 67.7 (February 2016): 780-789.
PMID
26892413
Source
epmc
Published In
JACC - Journal of the American College of Cardiology
Volume
67
Issue
7
Publish Date
2016
Start Page
780
End Page
789
DOI
10.1016/j.jacc.2015.11.050

Adverse Cardiovascular Response to Aerobic Exercise Training: Is This a Concern?

Aerobic exercise training in sedentary individuals improves physical fitness and various cardiovascular (CV) biomarkers. Nevertheless, there has been controversy as to whether exercise training may adversely affect some biomarkers in a small segment of the population. The purpose of this study was to investigate whether clinically significant worsening of CV biomarkers was more prevalent among individuals randomized to a supervised endurance training program as compared with those randomized to a control condition.Baseline and end of study measurements of fasting insulin (FI), triglycerides (TG), resting systolic blood pressure (SBP), and HDL cholesterol (HDL-C) were obtained on 1188 healthy sedentary subjects from 4 clinical studies. Each study randomized subjects to 4- to 6-month supervised aerobic exercise programs or to a control group of no supervised exercise training. For each of the 4 CV biomarkers, we calculated the respective proportions of control and exercise group subjects whose baseline-to-follow-up changes were greater than or equal to previously reported adverse change (AC) thresholds. Those thresholds were increases of 24 pmol · L(-1) or greater for FI, 0.42 mmol · L(-1) or greater for TG, 10 mm Hg or greater for SBP, and a decrease of 0.12 mmol · L(-1) or greater for HDL-C.The respective proportions of subjects meeting the AC threshold in the control and exercise groups were 15.2% versus 9.6% (P = 0.02) for FI, 14.9% versus 13.1% (P = 0.37) for TG, 16.9% versus 15.8% (P = 0.52) for SBP, and 28.6% versus 22.5% (P = 0.03) for HDL-C. All were nonsignificant at the 0.0125 Bonferroni threshold adjusting for multiple comparisons.These findings do not support the concept that aerobic exercise training increases the risk of adverse changes in the CV biomarkers we studied.

Authors
Leifer, ES; Mikus, CR; Karavirta, L; Resnick, BD; Kraus, WE; Häkkinen, K; Earnest, CP; Fleg, JL
MLA Citation
Leifer, ES, Mikus, CR, Karavirta, L, Resnick, BD, Kraus, WE, Häkkinen, K, Earnest, CP, and Fleg, JL. "Adverse Cardiovascular Response to Aerobic Exercise Training: Is This a Concern?." Medicine and science in sports and exercise 48.1 (January 2016): 20-25.
PMID
26258860
Source
epmc
Published In
Medicine and Science in Sports and Exercise
Volume
48
Issue
1
Publish Date
2016
Start Page
20
End Page
25
DOI
10.1249/mss.0000000000000752

Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of heart failure among older persons, are overweight or obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life (QOL).To determine whether caloric restriction (diet) or aerobic exercise training (exercise) improves exercise capacity and QOL in obese older patients with HFPEF.Randomized, attention-controlled, 2 × 2 factorial trial conducted from February 2009 through November 2014 in an urban academic medical center. Of 577 initially screened participants, 100 older obese participants (mean [SD]: age, 67 years [5]; body mass index, 39.3 [5.6]) with chronic, stable HFPEF were enrolled (366 excluded by inclusion and exclusion criteria, 31 for other reasons, and 80 declined participation).Twenty weeks of diet, exercise, or both; attention control consisted of telephone calls every 2 weeks.Exercise capacity measured as peak oxygen consumption (V̇O2, mL/kg/min; co-primary outcome) and QOL measured by the Minnesota Living with Heart Failure (MLHF) Questionnaire (score range: 0-105, higher scores indicate worse heart failure-related QOL; co-primary outcome).Of the 100 enrolled participants, 26 participants were randomized to exercise; 24 to diet; 25 to exercise + diet; 25 to control. Of these, 92 participants completed the trial. Exercise attendance was 84% (SD, 14%) and diet adherence was 99% (SD, 1%). By main effects analysis, peak V̇O2 was increased significantly by both interventions: exercise, 1.2 mL/kg body mass/min (95% CI, 0.7 to 1.7), P < .001; diet, 1.3 mL/kg body mass/min (95% CI, 0.8 to 1.8), P < .001. The combination of exercise + diet was additive (complementary) for peak V̇O2 (joint effect, 2.5 mL/kg/min). There was no statistically significant change in MLHF total score with exercise and with diet (main effect: exercise, -1 unit [95% CI, -8 to 5], P = .70; diet, -6 units [95% CI, -12 to 1], P = .08). The change in peak V̇O2 was positively correlated with the change in percent lean body mass (r = 0.32; P = .003) and the change in thigh muscle:intermuscular fat ratio (r = 0.27; P = .02). There were no study-related serious adverse events. Body weight decreased by 7% (7 kg [SD, 1]) in the diet group, 3% (4 kg [SD, 1]) in the exercise group, 10% (11 kg [SD, 1] in the exercise + diet group, and 1% (1 kg [SD, 1]) in the control group.Among obese older patients with clinically stable HFPEF, caloric restriction or aerobic exercise training increased peak V̇O2, and the effects may be additive. Neither intervention had a significant effect on quality of life as measured by the MLHF Questionnaire.clinicaltrials.gov Identifier: NCT00959660.

Authors
Kitzman, DW; Brubaker, P; Morgan, T; Haykowsky, M; Hundley, G; Kraus, WE; Eggebeen, J; Nicklas, BJ
MLA Citation
Kitzman, DW, Brubaker, P, Morgan, T, Haykowsky, M, Hundley, G, Kraus, WE, Eggebeen, J, and Nicklas, BJ. "Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial." JAMA 315.1 (January 2016): 36-46.
PMID
26746456
Source
epmc
Published In
JAMA : the journal of the American Medical Association
Volume
315
Issue
1
Publish Date
2016
Start Page
36
End Page
46
DOI
10.1001/jama.2015.17346

Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support.

Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these changes remain unclear.This study sought to describe the metabolomic profiles of patients along the spectrum of systolic HF, determine their association with adverse outcomes in a clinical trial of HF, and evaluate whether identified metabolites change with treatment for end-stage systolic HF.To assess association of metabolites with clinical outcomes, we evaluated a population of 453 chronic systolic HF patients who had been randomized to exercise training versus usual care. To assess change in metabolites with mechanical circulatory support, 41 patients with end-stage HF who underwent left ventricular assist device (LVAD) placement were studied. Targeted, quantitative profiling of 60 metabolites using tandem flow injection mass spectrometry was performed on frozen plasma samples obtained prior to randomization, as well as prior to and ≥90 days post-placement in the LVAD group. Principal components analysis was used for data reduction.Five principal components analysis-derived factors were significantly associated with peak Vo2 levels at baseline in fully adjusted models. Of these, factor 5 (composed of long-chain acylcarnitines) was associated with increased risk of all 3 pre-specified clinical trial outcomes: all-cause mortality/all-cause hospitalization, all cause-hospitalization, and cardiovascular death or cardiovascular hospitalization. Individual components of factor 5 were significantly higher in patients with end-stage HF prior to LVAD placement and decreased significantly post-implantation.In chronic HF patients, circulating long-chain acylcarnitine metabolite levels were independently associated with adverse clinical outcomes and decreased after long-term mechanical circulatory support. These metabolites may serve as potential targets for new diagnostics or therapeutic interventions. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Authors
Ahmad, T; Kelly, JP; McGarrah, RW; Hellkamp, AS; Fiuzat, M; Testani, JM; Wang, TS; Verma, A; Samsky, MD; Donahue, MP; Ilkayeva, OR; Bowles, DE; Patel, CB; Milano, CA; Rogers, JG; Felker, GM; O'Connor, CM; Shah, SH; Kraus, WE
MLA Citation
Ahmad, T, Kelly, JP, McGarrah, RW, Hellkamp, AS, Fiuzat, M, Testani, JM, Wang, TS, Verma, A, Samsky, MD, Donahue, MP, Ilkayeva, OR, Bowles, DE, Patel, CB, Milano, CA, Rogers, JG, Felker, GM, O'Connor, CM, Shah, SH, and Kraus, WE. "Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support." Journal of the American College of Cardiology 67.3 (January 2016): 291-299.
PMID
26796394
Source
epmc
Published In
JACC - Journal of the American College of Cardiology
Volume
67
Issue
3
Publish Date
2016
Start Page
291
End Page
299
DOI
10.1016/j.jacc.2015.10.079

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic ("traffic exposure")-a recognized vascular disease risk factor-on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3' untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family, associated with PAD via an interaction with traffic air pollution exposure. These results also highlight the potential for interactions studies, particularly at the genome scale, to reveal novel biology linking environmental exposures to clinical outcomes.

Authors
Ward-Caviness, CK; Neas, LM; Blach, C; Haynes, CS; LaRocque-Abramson, K; Grass, E; Dowdy, E; Devlin, RB; Diaz-Sanchez, D; Cascio, WE; Lynn Miranda, M; Gregory, SG; Shah, SH; Kraus, WE; Hauser, ER
MLA Citation
Ward-Caviness, CK, Neas, LM, Blach, C, Haynes, CS, LaRocque-Abramson, K, Grass, E, Dowdy, E, Devlin, RB, Diaz-Sanchez, D, Cascio, WE, Lynn Miranda, M, Gregory, SG, Shah, SH, Kraus, WE, and Hauser, ER. "Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease." PloS one 11.4 (January 2016): e0152670-.
PMID
27082954
Source
epmc
Published In
PloS one
Volume
11
Issue
4
Publish Date
2016
Start Page
e0152670
DOI
10.1371/journal.pone.0152670

Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship.

Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs-rs1462845 and rs6788787-using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01-1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69-0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08-1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05-1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects on survival. Additional analyses demonstrated that the homozygous risk genotype ('A/A') fully explained the increased hazard in both cohorts. None of the post-hoc analyses in control subjects were significant for any model. This suggests that genetic effects of rs1462845 on survival are unique to CAD presence. This represents formal, replicated evidence of genetic contribution of rs1462845 to increased risk for all-cause mortality; the contribution is unique to CAD case status and specific to males with severe burden of CAD.

Authors
Dungan, JR; Qin, X; Horne, BD; Carlquist, JF; Singh, A; Hurdle, M; Grass, E; Haynes, C; Gregory, SG; Shah, SH; Hauser, ER; Kraus, WE
MLA Citation
Dungan, JR, Qin, X, Horne, BD, Carlquist, JF, Singh, A, Hurdle, M, Grass, E, Haynes, C, Gregory, SG, Shah, SH, Hauser, ER, and Kraus, WE. "Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship." PloS one 11.5 (January 2016): e0154856-.
PMID
27187494
Source
epmc
Published In
PloS one
Volume
11
Issue
5
Publish Date
2016
Start Page
e0154856
DOI
10.1371/journal.pone.0154856

Deaths in triathletes: immersion pulmonary oedema as a possible cause.

To address the question as to whether immersion pulmonary oedema (IPO) may be a common cause of death in triathlons, markers of swimming-induced pulmonary oedema (SIPO) susceptibility were sought in triathletes' postmortem examinations.Deaths while training for or during triathlon events in the USA and Canada from October 2008 to November 2015 were identified, and postmortem reports requested. We assessed obvious causes of death; the prevalence of left ventricular hypertrophy (LVH); comparison with healthy triathletes.We identified 58 deaths during the time period of the review, 42 (72.4%) of which occurred during a swim. Of these, 23 postmortem reports were obtained. Five individuals had significant (≥70%) coronary artery narrowing; one each had coronary stents; retroperitoneal haemorrhage; or aortic dissection. 9 of 20 (45%) with reported heart mass exceeded 95th centile values. LV free wall and septal thickness were reported in 14 and 9 cases, respectively; of these, 6 (42.9%) and 4 (44.4%) cases exceeded normal values. 6 of 15 individuals (40%) without an obvious cause of death had excessive heart mass. The proportion of individuals with LVH exceeded the prevalence in the general triathlete population.LVH-a marker of SIPO susceptibility-was present in a greater than the expected proportion of triathletes who died during the swim portion. We propose that IPO may be a significant aetiology of death during the swimming phase in triathletes. The importance of testing for LVH in triathletes as a predictor of adverse outcomes should be explored further.

Authors
Moon, RE; Martina, SD; Peacher, DF; Kraus, WE
MLA Citation
Moon, RE, Martina, SD, Peacher, DF, and Kraus, WE. "Deaths in triathletes: immersion pulmonary oedema as a possible cause." BMJ open sport & exercise medicine 2.1 (January 2016): e000146-.
Website
http://hdl.handle.net/10161/13293
PMID
27900191
Source
epmc
Published In
BMJ Open Sport and Exercise Medicine
Volume
2
Issue
1
Publish Date
2016
Start Page
e000146

The effects of exercise on the lipoprotein subclass profile: A meta-analysis of 10 interventions.

The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts.Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group.Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value.Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk.

Authors
Sarzynski, MA; Burton, J; Rankinen, T; Blair, SN; Church, TS; Després, J-P; Hagberg, JM; Landers-Ramos, R; Leon, AS; Mikus, CR; Rao, DC; Seip, RL; Skinner, JS; Slentz, CA; Thompson, PD; Wilund, KR; Kraus, WE; Bouchard, C
MLA Citation
Sarzynski, MA, Burton, J, Rankinen, T, Blair, SN, Church, TS, Després, J-P, Hagberg, JM, Landers-Ramos, R, Leon, AS, Mikus, CR, Rao, DC, Seip, RL, Skinner, JS, Slentz, CA, Thompson, PD, Wilund, KR, Kraus, WE, and Bouchard, C. "The effects of exercise on the lipoprotein subclass profile: A meta-analysis of 10 interventions." Atherosclerosis 243.2 (December 2015): 364-372.
PMID
26520888
Source
epmc
Published In
Atherosclerosis
Volume
243
Issue
2
Publish Date
2015
Start Page
364
End Page
372
DOI
10.1016/j.atherosclerosis.2015.10.018

Incorporation of pharmacogenetic testing into medication therapy management.

To assess feasibility and patient satisfaction with a pharmacist-delivered medication therapy management (MTM) plus pharmacogenetic (PGx) testing service.Thirty patients from a cardiology outpatient clinic were enrolled to attend two MTM sessions, undergo PGx testing and complete pre- and post-intervention surveys. Outcome measures included duration of MTM sessions, clinical application of test results, self-reported medication adherence, patient recall of results and perceived value of testing and MTM.Overall, patients were very satisfied with the MTM plus PGx testing service. About half of participants (47%) were able to accurately recall their PGx test results. Comparable to MTM without PGx testing, the first MTM session averaged 40 min and the follow-up MTM session averaged 15 min.PGx testing incorporated into a clinical MTM service offered by pharmacists may be a feasible delivery model and is satisfactory to patients.

Authors
Haga, SB; Moaddeb, J; Mills, R; Patel, M; Kraus, W; Allen LaPointe, NM
MLA Citation
Haga, SB, Moaddeb, J, Mills, R, Patel, M, Kraus, W, and Allen LaPointe, NM. "Incorporation of pharmacogenetic testing into medication therapy management." Pharmacogenomics 16.17 (November 10, 2015): 1931-1941.
PMID
26555559
Source
epmc
Published In
Pharmacogenomics
Volume
16
Issue
17
Publish Date
2015
Start Page
1931
End Page
1941
DOI
10.2217/pgs.15.124

Implications of Angina Pectoris on Quality of Life, Functional Capacity and Clinical Outcomes in Chronic Heart Failure Patients: Insights From HF-ACTION

Authors
Mentz, RJ; Parikh, K; Coles, A; Schulte, PJ; Kraus, WE; Fleg, JL; Keteyian, SJ; Pina, IL; Fiuzat, M; Whellan, DJ; O'Connor, CM
MLA Citation
Mentz, RJ, Parikh, K, Coles, A, Schulte, PJ, Kraus, WE, Fleg, JL, Keteyian, SJ, Pina, IL, Fiuzat, M, Whellan, DJ, and O'Connor, CM. "Implications of Angina Pectoris on Quality of Life, Functional Capacity and Clinical Outcomes in Chronic Heart Failure Patients: Insights From HF-ACTION." November 10, 2015.
Source
wos-lite
Published In
Circulation
Volume
132
Publish Date
2015

Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis.

Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA), long-chain dicarboxylacylcarnitine (LCDA) and medium chain acylcarnitine (MCA) metabolites are heritable and predict cardiovascular disease (CVD) events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490), we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER) stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1) These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6-2.3x10-10). Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2). Expression quantitative trait loci (eQTL) pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS) arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk.

Authors
Kraus, WE; Muoio, DM; Stevens, R; Craig, D; Bain, JR; Grass, E; Haynes, C; Kwee, L; Qin, X; Slentz, DH; Krupp, D; Muehlbauer, M; Hauser, ER; Gregory, SG; Newgard, CB; Shah, SH
MLA Citation
Kraus, WE, Muoio, DM, Stevens, R, Craig, D, Bain, JR, Grass, E, Haynes, C, Kwee, L, Qin, X, Slentz, DH, Krupp, D, Muehlbauer, M, Hauser, ER, Gregory, SG, Newgard, CB, and Shah, SH. "Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis." PLoS genetics 11.11 (November 5, 2015): e1005553-.
Website
http://hdl.handle.net/10161/10957
PMID
26540294
Source
epmc
Published In
PLoS genetics
Volume
11
Issue
11
Publish Date
2015
Start Page
e1005553
DOI
10.1371/journal.pgen.1005553

A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience.

The CATHeterization GENetics (CATHGEN) biorepository was assembled in four phases. First, project start-up began in 2000. Second, between 2001 and 2010, we collected clinical data and biological samples from 9334 individuals undergoing cardiac catheterization. Samples were matched at the individual level to clinical data collected at the time of catheterization and stored in the Duke Databank for Cardiovascular Diseases (DDCD). Clinical data included the following: subject demographics (birth date, race, gender, etc.); cardiometabolic history including symptoms; coronary anatomy and cardiac function at catheterization; and fasting chemistry data. Third, as part of the DDCD regular follow-up protocol, yearly evaluations included interim information: vital status (verified via National Death Index search and supplemented by Social Security Death Index search), myocardial infarction (MI), stroke, rehospitalization, coronary revascularization procedures, medication use, and lifestyle habits including smoking. Fourth, samples were used to generate molecular data. CATHGEN offers the opportunity to discover biomarkers and explore mechanisms of cardiovascular disease.

Authors
Kraus, WE; Granger, CB; Sketch, MH; Donahue, MP; Ginsburg, GS; Hauser, ER; Haynes, C; Newby, LK; Hurdle, M; Dowdy, ZE; Shah, SH
MLA Citation
Kraus, WE, Granger, CB, Sketch, MH, Donahue, MP, Ginsburg, GS, Hauser, ER, Haynes, C, Newby, LK, Hurdle, M, Dowdy, ZE, and Shah, SH. "A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience." Journal of cardiovascular translational research 8.8 (November 2015): 449-457. (Review)
PMID
26271459
Source
epmc
Published In
Journal of Cardiovascular Translational Research
Volume
8
Issue
8
Publish Date
2015
Start Page
449
End Page
457
DOI
10.1007/s12265-015-9648-y

Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial.

Resistant hypertension (RH) is a growing health burden in this country affecting as many as 1 in 5 adults being treated for hypertension. Resistant hypertension is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure (BP) in this high-risk population are a national priority.TRIUMPH is a single-site, prospective, randomized clinical trial to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie Dietary Approaches to Stop Hypertension eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (n = 150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic BP; secondary end points include ambulatory BP and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, BP, and CVD risk factors also will be measured at 1-year follow-up.The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on BP and CVD biomarkers in patients with RH after 4 months of treatment and will determine whether lifestyle changes can be maintained for a year.

Authors
Blumenthal, JA; Sherwood, A; Smith, PJ; Mabe, S; Watkins, L; Lin, P-H; Craighead, LW; Babyak, M; Tyson, C; Young, K; Ashworth, M; Kraus, W; Liao, L; Hinderliter, A
MLA Citation
Blumenthal, JA, Sherwood, A, Smith, PJ, Mabe, S, Watkins, L, Lin, P-H, Craighead, LW, Babyak, M, Tyson, C, Young, K, Ashworth, M, Kraus, W, Liao, L, and Hinderliter, A. "Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial." American heart journal 170.5 (November 2015): 986-994.e5.
PMID
26542509
Source
epmc
Published In
American Heart Journal
Volume
170
Issue
5
Publish Date
2015
Start Page
986
End Page
994.e5
DOI
10.1016/j.ahj.2015.08.006

Psychosocial Factors, Exercise Adherence, and Outcomes in Heart Failure Patients: Insights From Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION).

Psychosocial factors may influence adherence with exercise training for heart failure (HF) patients. We aimed to describe the association between social support and barriers to participation with exercise adherence and clinical outcomes.Of patients enrolled in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION), 2279 (97.8%) completed surveys to assess social support and barriers to exercise, resulting in the perceived social support score (PSSS) and barriers to exercise score (BTES). Higher PSSS indicated higher levels of social support, whereas higher BTES indicated more barriers to exercise. Exercise time at 3 and 12 months correlated with PSSS (r= 0.09 and r= 0.13, respectively) and BTES (r=-0.11 and r=-0.12, respectively), with higher exercise time associated with higher PSSS and lower BTES (All P<0.005). For cardiovascular death or HF hospitalization, there was a significant interaction between the randomization group and BTES (P=0.035), which corresponded to a borderline association between increasing BTES and cardiovascular death or HF hospitalization in the exercise group (hazard ratio 1.25, 95% confidence interval 0.99, 1.59), but no association in the usual care group (hazard ratio 0.83, 95% confidence interval 0.66, 1.06).Poor social support and high barriers to exercise were associated with lower exercise time. PSSS did not impact the effect of exercise training on outcomes. However, for cardiovascular death or HF hospitalization, exercise training had a greater impact on patients with lower BTES. Given that exercise training improves outcomes in HF patients, assessment of perceived barriers may facilitate individualized approaches to implement exercise training therapy in clinical practice.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Authors
Cooper, LB; Mentz, RJ; Sun, J-L; Schulte, PJ; Fleg, JL; Cooper, LS; Piña, IL; Leifer, ES; Kraus, WE; Whellan, DJ; Keteyian, SJ; O'Connor, CM
MLA Citation
Cooper, LB, Mentz, RJ, Sun, J-L, Schulte, PJ, Fleg, JL, Cooper, LS, Piña, IL, Leifer, ES, Kraus, WE, Whellan, DJ, Keteyian, SJ, and O'Connor, CM. "Psychosocial Factors, Exercise Adherence, and Outcomes in Heart Failure Patients: Insights From Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)." Circulation. Heart failure 8.6 (November 2015): 1044-1051.
PMID
26578668
Source
epmc
Published In
Circulation: Heart Failure
Volume
8
Issue
6
Publish Date
2015
Start Page
1044
End Page
1051
DOI
10.1161/circheartfailure.115.002327

Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients.

The relationship between traffic-related air pollution (TRAP) and risk factors for cardiovascular disease needs to be better understood in order to address the adverse impact of air pollution on human health.We examined associations between roadway proximity and traffic exposure zones, as markers of TRAP exposure, and metabolic biomarkers for cardiovascular disease risk in a cohort of patients undergoing cardiac catheterization.We performed a cross-sectional study of 2,124 individuals residing in North Carolina (USA). Roadway proximity was assessed via distance to primary and secondary roadways, and we used residence in traffic exposure zones (TEZs) as a proxy for TRAP. Two categories of metabolic outcomes were studied: measures associated with glucose control, and measures associated with lipid metabolism. Statistical models were adjusted for race, sex, smoking, body mass index, and socioeconomic status (SES).An interquartile-range (990 m) decrease in distance to roadways was associated with higher fasting plasma glucose (β = 2.17 mg/dL; 95% CI: -0.24, 4.59), and the association appeared to be limited to women (β = 5.16 mg/dL; 95% CI: 1.48, 8.84 compared with β = 0.14 mg/dL; 95% CI: -3.04, 3.33 in men). Residence in TEZ 5 (high-speed traffic) and TEZ 6 (stop-and-go traffic), the two traffic zones assumed to have the highest levels of TRAP, was positively associated with high-density lipoprotein cholesterol (HDL-C; β = 8.36; 95% CI: -0.15, 16.9 and β = 5.98; 95% CI: -3.96, 15.9, for TEZ 5 and 6, respectively).Proxy measures of TRAP exposure were associated with intermediate metabolic traits associated with cardiovascular disease, including fasting plasma glucose and possibly HDL-C.

Authors
Ward-Caviness, CK; Kraus, WE; Blach, C; Haynes, CS; Dowdy, E; Miranda, ML; Devlin, RB; Diaz-Sanchez, D; Cascio, WE; Mukerjee, S; Stallings, C; Smith, LA; Gregory, SG; Shah, SH; Hauser, ER; Neas, LM
MLA Citation
Ward-Caviness, CK, Kraus, WE, Blach, C, Haynes, CS, Dowdy, E, Miranda, ML, Devlin, RB, Diaz-Sanchez, D, Cascio, WE, Mukerjee, S, Stallings, C, Smith, LA, Gregory, SG, Shah, SH, Hauser, ER, and Neas, LM. "Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients." Environmental health perspectives 123.10 (October 2015): 1007-1014.
PMID
25807578
Source
epmc
Published In
Environmental health perspectives
Volume
123
Issue
10
Publish Date
2015
Start Page
1007
End Page
1014
DOI
10.1289/ehp.1306980

Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.

Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.

Authors
Stafford-Smith, M; Li, Y-J; Mathew, JP; Li, Y-W; Ji, Y; Phillips-Bute, BG; Milano, CA; Newman, MF; Kraus, WE; Kertai, MD; Shah, SH; Podgoreanu, MV
MLA Citation
Stafford-Smith, M, Li, Y-J, Mathew, JP, Li, Y-W, Ji, Y, Phillips-Bute, BG, Milano, CA, Newman, MF, Kraus, WE, Kertai, MD, Shah, SH, and Podgoreanu, MV. "Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci." Kidney international 88.4 (October 2015): 823-832.
Website
http://hdl.handle.net/10161/13721
PMID
26083657
Source
epmc
Published In
Kidney international
Volume
88
Issue
4
Publish Date
2015
Start Page
823
End Page
832
DOI
10.1038/ki.2015.161

Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans.

Obesity is associated with decreased insulin sensitivity (IS) and elevated plasma branched-chain amino acids (BCAAs). The purpose of this study was to investigate the relationship between BCAA metabolism and IS in overweight (OW) individuals during exercise intervention.Whole-body leucine turnover, IS by hyperinsulinaemic-euglycaemic clamp, and circulating and skeletal muscle amino acids, branched-chain α-keto acids and acylcarnitines were measured in ten healthy controls (Control) and nine OW, untrained, insulin-resistant individuals (OW-Untrained). OW-Untrained then underwent a 6 month aerobic and resistance exercise programme and repeated testing (OW-Trained).IS was higher in Control vs OW-Untrained and increased significantly following exercise. IS was lower in OW-Trained vs Control expressed relative to body mass, but was not different from Control when normalised to fat-free mass (FFM). Plasma BCAAs and leucine turnover (relative to FFM) were higher in OW-Untrained vs Control, but did not change on average with exercise. Despite this, within individuals, the decrease in molar sum of circulating BCAAs was the best metabolic predictor of improvement in IS. Circulating glycine levels were higher in Control and OW-Trained vs OW-Untrained, and urinary metabolic profiling suggests that exercise induces more efficient elimination of excess acyl groups derived from BCAA and aromatic amino acid (AA) metabolism via formation of urinary glycine adducts.A mechanism involving more efficient elimination of excess acyl groups derived from BCAA and aromatic AA metabolism via glycine conjugation in the liver, rather than increased BCAA disposal through oxidation and turnover, may mediate interactions between exercise, BCAA metabolism and IS.Clinicaltrials.gov NCT01786941.

Authors
Glynn, EL; Piner, LW; Huffman, KM; Slentz, CA; Elliot-Penry, L; AbouAssi, H; White, PJ; Bain, JR; Muehlbauer, MJ; Ilkayeva, OR; Stevens, RD; Porter Starr, KN; Bales, CW; Volpi, E; Brosnan, MJ; Trimmer, JK; Rolph, TP; Newgard, CB; Kraus, WE
MLA Citation
Glynn, EL, Piner, LW, Huffman, KM, Slentz, CA, Elliot-Penry, L, AbouAssi, H, White, PJ, Bain, JR, Muehlbauer, MJ, Ilkayeva, OR, Stevens, RD, Porter Starr, KN, Bales, CW, Volpi, E, Brosnan, MJ, Trimmer, JK, Rolph, TP, Newgard, CB, and Kraus, WE. "Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans." Diabetologia 58.10 (October 2015): 2324-2335.
PMID
26254576
Source
epmc
Published In
Diabetologia
Volume
58
Issue
10
Publish Date
2015
Start Page
2324
End Page
2335
DOI
10.1007/s00125-015-3705-6

Gene Expression Profiling Reflects Increased Expression of Coronary Artery Disease Associated Genes in a Case-Control Matched Study of Patient with Rheumatoid Arthritis

Authors
Peart, E; Huffman, K; Kraus, WE; Beineke, P; Wingrove, J; Rosenberg, S
MLA Citation
Peart, E, Huffman, K, Kraus, WE, Beineke, P, Wingrove, J, and Rosenberg, S. "Gene Expression Profiling Reflects Increased Expression of Coronary Artery Disease Associated Genes in a Case-Control Matched Study of Patient with Rheumatoid Arthritis." ARTHRITIS & RHEUMATOLOGY 67 (October 2015).
Source
wos-lite
Published In
Arthritis and Rheumatology
Volume
67
Publish Date
2015

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health.One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD.We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

Authors
Sood, S; Gallagher, IJ; Lunnon, K; Rullman, E; Keohane, A; Crossland, H; Phillips, BE; Cederholm, T; Jensen, T; van Loon, LJC; Lannfelt, L; Kraus, WE; Atherton, PJ; Howard, R; Gustafsson, T; Hodges, A; Timmons, JA
MLA Citation
Sood, S, Gallagher, IJ, Lunnon, K, Rullman, E, Keohane, A, Crossland, H, Phillips, BE, Cederholm, T, Jensen, T, van Loon, LJC, Lannfelt, L, Kraus, WE, Atherton, PJ, Howard, R, Gustafsson, T, Hodges, A, and Timmons, JA. "A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status." Genome biology 16 (September 7, 2015): 185-.
PMID
26343147
Source
epmc
Published In
Genome Biology: biology for the post-genomic era
Volume
16
Publish Date
2015
Start Page
185
DOI
10.1186/s13059-015-0750-x

A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.

Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR.To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-α (secondary); and exploratory physiological and psychological measures.Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7±0.7 %CR (mean ± standard error) and maintained 10.4±0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p < .001), while tumor necrosis factor-α decreased significantly more only at M24 (p = .02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life.Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.

Authors
Ravussin, E; Redman, LM; Rochon, J; Das, SK; Fontana, L; Kraus, WE; Romashkan, S; Williamson, DA; Meydani, SN; Villareal, DT; Smith, SR; Stein, RI; Scott, TM; Stewart, TM; Saltzman, E; Klein, S; Bhapkar, M; Martin, CK; Gilhooly, CH; Holloszy, JO; Hadley, EC; Roberts, SB
MLA Citation
Ravussin, E, Redman, LM, Rochon, J, Das, SK, Fontana, L, Kraus, WE, Romashkan, S, Williamson, DA, Meydani, SN, Villareal, DT, Smith, SR, Stein, RI, Scott, TM, Stewart, TM, Saltzman, E, Klein, S, Bhapkar, M, Martin, CK, Gilhooly, CH, Holloszy, JO, Hadley, EC, and Roberts, SB. "A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity." The journals of gerontology. Series A, Biological sciences and medical sciences 70.9 (September 2015): 1097-1104.
PMID
26187233
Source
epmc
Published In
Journals of Gerontology: Series A
Volume
70
Issue
9
Publish Date
2015
Start Page
1097
End Page
1104
DOI
10.1093/gerona/glv057

Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene.

Chronic psychosocial stress adversely affects health and is associated with the development of disease [Williams, 2008]. Systematic epidemiological and genetic studies are needed to uncover genetic variants that interact with stress to modify metabolic responses across the life cycle that are the proximal contributors to the development of cardiovascular disease and precipitation of acute clinical events. Among the central challenges in the field are to perform and replicate gene-by-environment (G × E) studies. The challenge of measurement of individual experience of psychosocial stress is magnified in this context. Although many research datasets exist that contain genotyping and disease-related data, measures of psychosocial stress are often either absent or vary substantially across studies. In this paper, we provide an algorithm to create a synthetic measure of chronic psychosocial stress across multiple datasets, applying a consistent criterion that uses proxy indicators of stress components. We validated the computed scores of chronic psychosocial stress by observing moderately strong and significant correlations with the self-rated chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis Cohort (Rho = 0.23, P < 0.0001) and with the measures of depressive symptoms in five datasets (Rho = 0.15-0.42, Ps = 0.005 to <0.0001) and by comparing the distributions of the self-rated and computed measures. Finally, we demonstrate the utility of this computed chronic psychosocial stress variable by providing three additional replications of our previous finding of gene-by-stress interaction with central obesity traits [Singh et al., 2015].

Authors
Singh, A; Babyak, MA; Brummett, BH; Jiang, R; Watkins, LL; Barefoot, JC; Kraus, WE; Shah, SH; Siegler, IC; Hauser, ER; Williams, RB
MLA Citation
Singh, A, Babyak, MA, Brummett, BH, Jiang, R, Watkins, LL, Barefoot, JC, Kraus, WE, Shah, SH, Siegler, IC, Hauser, ER, and Williams, RB. "Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene." Genetic epidemiology 39.6 (September 2015): 489-497.
PMID
26202568
Source
epmc
Published In
Genetic Epidemiology
Volume
39
Issue
6
Publish Date
2015
Start Page
489
End Page
497
DOI
10.1002/gepi.21910

Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery.

Postoperative atrial fibrillation (AF) is a potentially life-threatening complication after coronary artery bypass graft (CABG) surgery. Genetic predisposition may predict risk for developing postoperative AF.Study subjects underwent CABG surgery with cardiopulmonary bypass at Duke University Medical Center. In a discovery cohort of 877 individuals from the Perioperative Genetics and Safety Outcomes Study, we performed a genome-wide association study using a logistic regression model with a covariate adjustment for AF risk index. Single-nucleotide polymorphisms (SNPs) that met a P < 5 × 10(-5) were further tested using a replication dataset of 304 individuals from the CATHeterization GENetics biorepository, followed by meta-analysis. Potential pathways related to postoperative AF were identified through gene enrichment analysis using the top genome-wide association study SNPs (P < 10(-4)).Nineteen SNPs met the a priori defined discovery threshold for replication, but only 3 met nominal significance (P < .05) in the CATHeterization GENetics group, with only one-rs10504554, in the intronic region in lymphocyte antigen 96 (LY96)-showing the same direction of the effect for postoperative AF (odds ratio [OR] 0.48, 95% CI 0.34-0.68, P = 2.9 × 10(-5) vs OR 0.55, 95% CI 0.31-0.99, P = .046) and strong overall association by meta-analysis (meta-P = 4.0 × 10(-6)). Gene enrichment analysis highlighted the role of LY96 in pathways of biologic relevance to activation and modulation of innate immune responses. Our analysis also showed potential association between LY96 and nuclear factor κ-B interaction and postoperative AF through their relevance to inflammatory signaling pathways.In patients undergoing CABG surgery, we found genetic polymorphisms in LY96 associated with decreased risk of postoperative AF.

Authors
Kertai, MD; Li, Y-J; Ji, Y; Qi, W; Lombard, FW; Shah, SH; Kraus, WE; Stafford-Smith, M; Newman, MF; Milano, CA; Waldron, N; Podgoreanu, MV; Mathew, JP
MLA Citation
Kertai, MD, Li, Y-J, Ji, Y, Qi, W, Lombard, FW, Shah, SH, Kraus, WE, Stafford-Smith, M, Newman, MF, Milano, CA, Waldron, N, Podgoreanu, MV, and Mathew, JP. "Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery." American heart journal 170.3 (September 2015): 580-90.e28.
PMID
26385043
Source
epmc
Published In
American Heart Journal
Volume
170
Issue
3
Publish Date
2015
Start Page
580
End Page
90.e28
DOI
10.1016/j.ahj.2015.06.009

Epigenetic profiling identifies novel genes for ascending aortic aneurysm formation with bicuspid aortic valves.

  Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized.  We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.  Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves.  Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays.  Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test.    Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4).  The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid patients, as compared to tricuspid patients.  Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including ACTA2 (4 probes, delta beta range:  -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissections  Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms.  The top gene was PTPN22, which is involved in T-cell receptor signaling and associated with various immune disorders.  These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.

Authors
Shah, AA; Gregory, SG; Krupp, D; Feng, S; Dorogi, A; Haynes, C; Grass, E; Lin, SS; Hauser, ER; Kraus, WE; Shah, SH; Hughes, GC
MLA Citation
Shah, AA, Gregory, SG, Krupp, D, Feng, S, Dorogi, A, Haynes, C, Grass, E, Lin, SS, Hauser, ER, Kraus, WE, Shah, SH, and Hughes, GC. "Epigenetic profiling identifies novel genes for ascending aortic aneurysm formation with bicuspid aortic valves." The heart surgery forum 18.4 (August 30, 2015): E134-E139.
PMID
26334848
Source
epmc
Published In
The heart surgery forum
Volume
18
Issue
4
Publish Date
2015
Start Page
E134
End Page
E139
DOI
10.1532/hsf.1247

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study.

While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity.Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively.Multinational study of 9306 participants.Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme.Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included.Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ(2)=16.8; p<0.0001), but not change in weight (χ(2)=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ(2)=5.9; p=0.02) but not previous step count (χ(2)=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ(2) for previous weight measurements 747.3; p<0.0001) and physical activity (χ(2) for previous step count 432.6; p<0.0001), these effects were of limited clinical importance.While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables.NCT00097786.

Authors
Preiss, D; Thomas, LE; Wojdyla, DM; Haffner, SM; Gill, JMR; Yates, T; Davies, MJ; Holman, RR; McMurray, JJ; Califf, RM; Kraus, WE
MLA Citation
Preiss, D, Thomas, LE, Wojdyla, DM, Haffner, SM, Gill, JMR, Yates, T, Davies, MJ, Holman, RR, McMurray, JJ, Califf, RM, and Kraus, WE. "Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study." BMJ open 5.8 (August 14, 2015): e007901-.
PMID
26275900
Source
epmc
Published In
BMJ Open
Volume
5
Issue
8
Publish Date
2015
Start Page
e007901
DOI
10.1136/bmjopen-2015-007901

Physical activity as a determinant of fasting and 2-h post-challenge glucose: a prospective cohort analysis of the NAVIGATOR trial.

To investigate whether previous physical activity levels are associated with blood glucose levels in individuals with impaired glucose tolerance in the context of an international pharmaceutical trial.Data were analysed from the NAVIGATOR trial, which involved 9306 individuals with impaired glucose tolerance and high cardiovascular risk from 40 different countries, recruited in the period 2002-2004. Fasting glucose, 2-h post-challenge glucose and physical activity (pedometer) were assessed annually. A longitudinal regression analysis was used to determine whether physical activity levels 2 years (t-2 ) and 1 year (t-1 ) previously were associated with levels of glucose, after adjusting for previous glucose levels and other patient characteristics. Those participants with four consecutive annual measures of glucose and two consecutive measures of physical activity were included in the analysis.The analysis included 3964 individuals. Change in physical activity from t-2 to t-1 and activity levels at t-2 were both associated with 2-h glucose levels after adjustment for previous glucose levels and baseline characteristics; however, the associations were weak: a 100% increase in physical activity was associated with a 0.9% reduction in 2-h glucose levels. In addition, previous physical activity only explained an additional 0.05% of the variance in 2-h glucose over the variance explained by the history of 2-h glucose alone (R(2)  = 0.3473 vs. 0.3468). There was no association with fasting glucose.In the context of a large international clinical trial, previous physical activity levels did not meaningfully influence glucose levels in those with a high risk of chronic disease, after taking into account participants' previous trajectory of glucose control.

Authors
Yates, T; Davies, MJ; Haffner, SM; Schulte, PJ; Thomas, L; Huffman, KM; Bales, CW; Preiss, D; Califf, RM; Holman, RR; McMurray, JJV; Bethel, MA; Tuomilehto, J; Kraus, WE
MLA Citation
Yates, T, Davies, MJ, Haffner, SM, Schulte, PJ, Thomas, L, Huffman, KM, Bales, CW, Preiss, D, Califf, RM, Holman, RR, McMurray, JJV, Bethel, MA, Tuomilehto, J, and Kraus, WE. "Physical activity as a determinant of fasting and 2-h post-challenge glucose: a prospective cohort analysis of the NAVIGATOR trial." Diabetic medicine : a journal of the British Diabetic Association 32.8 (August 2015): 1090-1096.
PMID
25818859
Source
epmc
Published In
Diabetic Medicine
Volume
32
Issue
8
Publish Date
2015
Start Page
1090
End Page
1096
DOI
10.1111/dme.12762

Incremental and independent value of cardiopulmonary exercise test measures and the Seattle Heart Failure Model for prediction of risk in patients with heart failure.

Multivariable risk scores and exercise measures are well-validated risk prediction methods. Combining information from a functional evaluation and a risk model may improve accuracy of risk predictions. We analyzed whether adding exercise measures to the Seattle Heart Failure Model (SHFM) improves risk prediction accuracy in systolic heart failure.We used a sample of patients from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) study (http://www.clinicaltrials.gov; unique identifier: NCT00047437) to examine the addition of peak oxygen consumption, expired volume per unit time/volume of carbon dioxide slope, 6-minute walk distance, or cardiopulmonary exercise duration to the SHFM. Multivariable Cox proportional hazards models were used to test the association between the combined end point (death, left ventricular assist device, or cardiac transplantation) and the addition of exercise variables to the SHFM.The sample included 2,152 patients. The SHFM and all exercise measures were associated with events (all p < 0.0001) in proportional hazards models. There was statistically significant improvement in risk estimation when exercise measures were added to the SHFM. However, the improvement in the C index for the addition of peak volume of oxygen consumption (+0.01), expired volume per unit time/volume of carbon dioxide slope (+0.02), 6-minute walk distance (-0.001), and cardiopulmonary exercise duration (+0.001) to the SHFM was small or slightly worse than the SHFM alone. Changes in risk assignment with the addition of exercise variables were minimal for patients above or below a 15% 1-year mortality.Exercise performance measures and the SHFM are independently useful for predicting risk in systolic heart failure. Adding cardiopulmonary exercise testing measures and 6MWD to the SHFM offers only minimal improvement in risk reassignment at clinically meaningful cut points.

Authors
Dardas, T; Li, Y; Reed, SD; O'Connor, CM; Whellan, DJ; Ellis, SJ; Schulman, KA; Kraus, WE; Forman, DE; Levy, WC
MLA Citation
Dardas, T, Li, Y, Reed, SD, O'Connor, CM, Whellan, DJ, Ellis, SJ, Schulman, KA, Kraus, WE, Forman, DE, and Levy, WC. "Incremental and independent value of cardiopulmonary exercise test measures and the Seattle Heart Failure Model for prediction of risk in patients with heart failure." The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 34.8 (August 2015): 1017-1023.
PMID
25940075
Source
epmc
Published In
The Journal of Heart and Lung Transplantation
Volume
34
Issue
8
Publish Date
2015
Start Page
1017
End Page
1023
DOI
10.1016/j.healun.2015.03.017

Novel Protein Glycan Inflammatory Biomarkers Predict Adverse Events in Heart Failure with Preserved Ejection Fraction

Authors
Kelly, JP; Hunter, WG; McGarrah, RW; Craig, D; Haynes, C; Velazquez, EJ; Felker, GM; Hernandez, AF; Newgard, CB; Shah, SH; Kraus, WE
MLA Citation
Kelly, JP, Hunter, WG, McGarrah, RW, Craig, D, Haynes, C, Velazquez, EJ, Felker, GM, Hernandez, AF, Newgard, CB, Shah, SH, and Kraus, WE. "Novel Protein Glycan Inflammatory Biomarkers Predict Adverse Events in Heart Failure with Preserved Ejection Fraction." August 2015.
Source
crossref
Published In
Journal of Cardiac Failure
Volume
21
Issue
8
Publish Date
2015
Start Page
S89
End Page
S89
DOI
10.1016/j.cardfail.2015.06.266

Evaluation of the Incremental Prognostic Utility of Increasingly Complex Testing in Chronic Heart Failure.

Current heart failure (HF) risk prediction models do not consider how individual patient assessments occur in incremental steps; furthermore, each additional diagnostic evaluation may add cost, complexity, and potential morbidity.Using a cohort of well-treated ambulatory HF patients with reduced ejection fraction who had complete clinical, laboratory, health-related quality of life, imaging, and exercise testing data, we estimated incremental prognostic information provided by 5 assessment categories, performing an additional analysis on those with available N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. We compared the incremental value of each additional assessment (quality of life screen, laboratory testing, echocardiography, and exercise testing) to baseline clinical assessment for predicting clinical outcomes (all-cause mortality, all-cause mortality/hospitalization, and cardiovascular death/HF hospitalizations), gauging incremental improvements in prognostic ability with more information using area under the curve and reclassification improvement (net reclassification index), with and without NT-proBNP availability. Of 2331 participants, 1631 patients had complete clinical data; of these, 1023 had baseline NT-proBNP. For prediction of all-cause mortality, models with incremental assessments sans NT-proBNP showed improvements in C-indices (0.72 [clinical model alone]-0.77 [complete model]). Compared with baseline clinical assessment alone, net reclassification index improved from 0.035 (w/laboratory data) to 0.085 (complete model). These improvements were significantly attenuated for models in the subset with measured NT-proBNP data (c-indices: 0.80 [w/laboratory data]-0.81 [full model]); net reclassification index improvements were similarly marginal (0.091→0.096); prediction of other clinical outcomes had similar findings.In chronic HF patients with reduced ejection fraction, the marginal benefit of complex prognostic evaluations should be weighed against potential patient discomfort and cost escalation.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Authors
Ahmad, T; O'Brien, EC; Schulte, PJ; Stevens, SR; Fiuzat, M; Kitzman, DW; Adams, KF; Kraus, WE; Piña, IL; Donahue, MP; Zannad, F; Whellan, DJ; O'Connor, CM; Felker, GM
MLA Citation
Ahmad, T, O'Brien, EC, Schulte, PJ, Stevens, SR, Fiuzat, M, Kitzman, DW, Adams, KF, Kraus, WE, Piña, IL, Donahue, MP, Zannad, F, Whellan, DJ, O'Connor, CM, and Felker, GM. "Evaluation of the Incremental Prognostic Utility of Increasingly Complex Testing in Chronic Heart Failure." Circulation. Heart failure 8.4 (July 2015): 709-716.
PMID
26034004
Source
epmc
Published In
Circulation: Heart Failure
Volume
8
Issue
4
Publish Date
2015
Start Page
709
End Page
716
DOI
10.1161/circheartfailure.114.001996

Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits." Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying "-omics" technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.

Authors
Neufer, PD; Bamman, MM; Muoio, DM; Bouchard, C; Cooper, DM; Goodpaster, BH; Booth, FW; Kohrt, WM; Gerszten, RE; Mattson, MP; Hepple, RT; Kraus, WE; Reid, MB; Bodine, SC; Jakicic, JM; Fleg, JL; Williams, JP; Joseph, L; Evans, M; Maruvada, P; Rodgers, M; Roary, M; Boyce, AT; Drugan, JK; Koenig, JI; Ingraham, RH; Krotoski, D; Garcia-Cazarin, M; McGowan, JA; Laughlin, MR
MLA Citation
Neufer, PD, Bamman, MM, Muoio, DM, Bouchard, C, Cooper, DM, Goodpaster, BH, Booth, FW, Kohrt, WM, Gerszten, RE, Mattson, MP, Hepple, RT, Kraus, WE, Reid, MB, Bodine, SC, Jakicic, JM, Fleg, JL, Williams, JP, Joseph, L, Evans, M, Maruvada, P, Rodgers, M, Roary, M, Boyce, AT, Drugan, JK, Koenig, JI, Ingraham, RH, Krotoski, D, Garcia-Cazarin, M, McGowan, JA, and Laughlin, MR. "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits." Cell metabolism 22.1 (July 2015): 4-11.
PMID
26073496
Source
epmc
Published In
Cell Metabolism
Volume
22
Issue
1
Publish Date
2015
Start Page
4
End Page
11
DOI
10.1016/j.cmet.2015.05.011

Physiology of sedentary behavior and its relationship to health outcomes.

This article reports on the findings and recommendations of the "Physiology of Sedentary Behavior and Its Relationship to Health Outcomes" group, a part of a larger workshop entitled Sedentary Behavior: Identifying Research Priorities sponsored by the National Heart, Lung, and Blood Institute and by the National Institute on Aging, which aimed to establish sedentary behavior research priorities.The discussion within our workshop led to the formation of critical physiological research objectives related to sedentary behaviors, that is, if appropriately researched, would greatly affect our overall understanding of human health and longevity.Primary questions are related to physiological "health outcomes" including the influence of physical activity versus sedentary behavior on the function of a number of critical physiological systems (aerobic capacity, skeletal muscle metabolism and function, telomeres/genetic stability, and cognitive function). The group also derived important recommendations related to the "central and peripheral mechanisms" that govern sedentary behavior and how energy balance has a role in mediating these processes. General recommendations for future sedentary physiology research efforts indicate that studies of sedentary behavior, including that of sitting time only, should focus on the physiological effect of a "lack of human movement" in contradistinction to the effects of physical movement and that new models or strategies for studying sedentary behavior-induced adaptations and links to disease development are needed to elucidate underlying mechanism(s).

Authors
Thyfault, JP; Du, M; Kraus, WE; Levine, JA; Booth, FW
MLA Citation
Thyfault, JP, Du, M, Kraus, WE, Levine, JA, and Booth, FW. "Physiology of sedentary behavior and its relationship to health outcomes." Medicine and science in sports and exercise 47.6 (June 2015): 1301-1305.
PMID
25222820
Source
epmc
Published In
Medicine and Science in Sports and Exercise
Volume
47
Issue
6
Publish Date
2015
Start Page
1301
End Page
1305
DOI
10.1249/mss.0000000000000518

Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene.

We performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps = 7.14E-09 to 2.33E-08, uncorrected; Ps = 1.99E-07 to 5.18E-07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps = 0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate = 0.26, P = 0.033, 95% CI = 0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate = 0.004, P = 0.34, 95% CI = -0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values = 0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease.

Authors
Singh, A; Babyak, MA; Nolan, DK; Brummett, BH; Jiang, R; Siegler, IC; Kraus, WE; Shah, SH; Williams, RB; Hauser, ER
MLA Citation
Singh, A, Babyak, MA, Nolan, DK, Brummett, BH, Jiang, R, Siegler, IC, Kraus, WE, Shah, SH, Williams, RB, and Hauser, ER. "Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene." European journal of human genetics : EJHG 23.6 (June 2015): 854-862.
PMID
25271088
Source
epmc
Published In
European Journal of Human Genetics
Volume
23
Issue
6
Publish Date
2015
Start Page
854
End Page
862
DOI
10.1038/ejhg.2014.189

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

Authors
AbouAssi, H; Slentz, CA; Mikus, CR; Tanner, CJ; Bateman, LA; Willis, LH; Shields, AT; Piner, LW; Penry, LE; Kraus, EA; Huffman, KM; Bales, CW; Houmard, JA; Kraus, WE
MLA Citation
AbouAssi, H, Slentz, CA, Mikus, CR, Tanner, CJ, Bateman, LA, Willis, LH, Shields, AT, Piner, LW, Penry, LE, Kraus, EA, Huffman, KM, Bales, CW, Houmard, JA, and Kraus, WE. "The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial." Journal of applied physiology (Bethesda, Md. : 1985) 118.12 (June 2015): 1474-1482.
PMID
25882384
Source
epmc
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
118
Issue
12
Publish Date
2015
Start Page
1474
End Page
1482
DOI
10.1152/japplphysiol.00509.2014

Prognostic significance of depression in blacks with heart failure: insights from Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training.

Although studies have shown that depression is associated with worse outcomes in patients with heart failure, most studies have been in white patients. The impact of depression on outcomes in blacks with heart failure has not been studied.We analyzed 747 blacks and 1420 whites enrolled in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training, which randomized 2331 patients with ejection fraction ≤35% to usual care with or without exercise training. We examined the association between depressive symptoms assessed by the Beck Depression Inventory-II (BDI-II) at baseline and after 3 months with all-cause mortality/hospitalization. A race by baseline BDI-II interaction was observed (P=0.003) in which elevated baseline scores were associated with worse outcomes in blacks versus whites. In blacks, the association was nonlinear with a hazard ratio of 1.44 (95% confidence interval, 1.24-1.68) when comparing the 75th and 25th percentile of BDI-II (score of 15 and 5, respectively). No race interaction was observed for mortality (P=0.34). There was no differential association between BDI-II change and outcomes in blacks versus whites. In blacks, an increase in BDI-II score from baseline to 3 months was associated with increased mortality/hospitalization (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57 per 10 point increase), whereas a decrease was not related to outcomes.In blacks with heart failure, baseline symptoms of depression and worsening of symptoms over time are associated with increased all-cause mortality/hospitalization. Routine assessment of depressive symptoms in blacks with heart failure may help guide management.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Authors
Mentz, RJ; Babyak, MA; Bittner, V; Fleg, JL; Keteyian, SJ; Swank, AM; Piña, IL; Kraus, WE; Whellan, DJ; O'Connor, CM; Blumenthal, JA
MLA Citation
Mentz, RJ, Babyak, MA, Bittner, V, Fleg, JL, Keteyian, SJ, Swank, AM, Piña, IL, Kraus, WE, Whellan, DJ, O'Connor, CM, and Blumenthal, JA. "Prognostic significance of depression in blacks with heart failure: insights from Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training." Circulation. Heart failure 8.3 (May 2015): 497-503.
PMID
25901047
Source
epmc
Published In
Circulation: Heart Failure
Volume
8
Issue
3
Publish Date
2015
Start Page
497
End Page
503
DOI
10.1161/circheartfailure.114.001995

The National Physical Activity Plan: a call to action from the American Heart Association: a science advisory from the American Heart Association.

Authors
Kraus, WE; Bittner, V; Appel, L; Blair, SN; Church, T; Després, J-P; Franklin, BA; Miller, TD; Pate, RR; Taylor-Piliae, RE; Vafiadis, DK; Whitsel, L
MLA Citation
Kraus, WE, Bittner, V, Appel, L, Blair, SN, Church, T, Després, J-P, Franklin, BA, Miller, TD, Pate, RR, Taylor-Piliae, RE, Vafiadis, DK, and Whitsel, L. "The National Physical Activity Plan: a call to action from the American Heart Association: a science advisory from the American Heart Association." Circulation 131.21 (May 2015): 1932-1940.
PMID
25918126
Source
epmc
Published In
Circulation
Volume
131
Issue
21
Publish Date
2015
Start Page
1932
End Page
1940
DOI
10.1161/cir.0000000000000203

Authorship in a multicenter clinical trial: The Heart Failure-A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) Authorship and Publication (HAP) scoring system results.

Few guidelines exist regarding authorship on manuscripts resulting from large multicenter trials. The HF-ACTION investigators devised a system to address assignment of authorship on trial publications and tested the outcomes in the course of conducting the large, multicenter, National Heart, Lung, and Blood Institute-funded trial (n = 2,331; 82 clinical sites; 3 countries). The HF-ACTION Authorship and Publication (HAP) scoring system was designed to enhance rate of dissemination, recognize investigator contributions to the successful conduct of the trial, and harness individual expertise in manuscript generation.The HAP score was generated by assigning points based on investigators' participation in trial enrollment, follow-up, and adherence, as well as participation in committees and other trial activity. Overall publication rates, publication rates by author, publication rates by site, and correlation between site publication and HAP score using a Poisson regression model were examined.Fifty peer-reviewed, original manuscripts were published within 6.5 years after conclusion of study enrollment. In total, 137 different authors were named in at least 1 publication. Forty-five (55%) of the 82 sites had an author named to at least 1 article. A Poisson regression model examining incident rate ratios revealed that a higher HAP score resulted in a higher incidence of a manuscript, with a 100-point increase in site score corresponding to an approximately 32% increase in the incidence of a published article.Given the success in publishing a large number of manuscripts and widely distributing authorship, regular use of a transparent, objective authorship assignment system for publishing results from multicenter trials may be recommended to optimize fairness and dissemination of trial results.

Authors
Whellan, DJ; Kraus, WE; Kitzman, DW; Rooney, B; Keteyian, SJ; Piña, IL; Ellis, SJ; Ghali, JK; Lee, KL; Cooper, LS; O'Connor, CM
MLA Citation
Whellan, DJ, Kraus, WE, Kitzman, DW, Rooney, B, Keteyian, SJ, Piña, IL, Ellis, SJ, Ghali, JK, Lee, KL, Cooper, LS, and O'Connor, CM. "Authorship in a multicenter clinical trial: The Heart Failure-A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) Authorship and Publication (HAP) scoring system results." American heart journal 169.4 (April 2015): 457-63.e6. (Review)
PMID
25819851
Source
epmc
Published In
American Heart Journal
Volume
169
Issue
4
Publish Date
2015
Start Page
457
End Page
63.e6
DOI
10.1016/j.ahj.2014.11.022

Genetic variants associated with vein graft stenosis after coronary artery bypass grafting.

Vein graft stenosis after coronary artery bypass grafting (CABG) is common. Identifying genes associated with vein graft stenosis after CABG could reveal novel mechanisms of disease and discriminate patients at risk for graft failure. We hypothesized that genome-wide association would identify these genes.We performed a genome-wide association study on a subset of patients presenting for cardiac catheterization for concern of ischemic heart disease, who also underwent CABG and subsequent coronary angiography after CABG for clinical indications (n = 521). Cases were defined as individuals with ≥50% stenosis in any vein graft on any cardiac catheterization, and controls were defined as those who did not have vein graft stenosis on any subsequent cardiac catheterization. Multivariable logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) and vein graft stenosis.Sixty-nine percent of patients had vein graft failure after CABG. Seven SNPs were significantly associated with vein graft stenosis, including intronic SNPs in the genes PALLD (Rs6854137, P = 3.77 × 10(-6)), ARID1B (Rs184074, P = 5.97 × 10(-6)), and TMEM123 (Rs11225247, P = 8.25 × 10(-6)); and intergenic SNPs near the genes ABCA13 (Rs10232860, P = 4.54 × 10(-6)), RMI2 (Rs9921338, P = 6.15 × 10(-6)), PRM2 (Rs7198849, P = 7.27 × 10(-6)), and TNFSF4 (Rs17346536, P = 9.33 × 10(-6)).We have identified novel genetic variants that may predispose to risk of vein graft failure after CABG, many within biologically plausible pathways. These polymorphisms merit further investigation, as they could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy.

Authors
Shah, AA; Haynes, C; Craig, DM; Sebek, J; Grass, E; Abramson, K; Hauser, E; Gregory, SG; Kraus, WE; Smith, PK; Shah, SH
MLA Citation
Shah, AA, Haynes, C, Craig, DM, Sebek, J, Grass, E, Abramson, K, Hauser, E, Gregory, SG, Kraus, WE, Smith, PK, and Shah, SH. "Genetic variants associated with vein graft stenosis after coronary artery bypass grafting." The heart surgery forum 18.1 (February 27, 2015): E1-E5.
PMID
25881214
Source
epmc
Published In
The heart surgery forum
Volume
18
Issue
1
Publish Date
2015
Start Page
E1
End Page
E5
DOI
10.1532/hsf.1214

Simultaneous consideration of multiple candidate protein biomarkers for long-term risk for cardiovascular events.

Although individual protein biomarkers are associated with cardiovascular risk, rarely have multiple proteins been considered simultaneously to identify which set of proteins best predicts risk.In a nested case-control study of 273 death/myocardial infarction (MI) cases and 273 age- (within 10 years), sex-, and race-matched and event-free controls from among 2023 consecutive patients (median follow-up 2.5 years) with suspected coronary disease, plasma levels of 53 previously reported biomarkers of cardiovascular risk were determined in a core laboratory. Three penalized logistic regression models were fit using the elastic net to identify panels of proteins independently associated with death/MI: proteins alone (Model 1); proteins in a model constrained to retain clinical variables (Model 2); and proteins and clinical variables available for selection (Model 3). Model 1 identified 6 biomarkers strongly associated with death/MI: intercellular adhesion molecule-1, matrix metalloproteinase-3, N-terminal pro-B-type natriuretic peptide, interleukin-6, soluble CD40 ligand, and insulin-like growth factor binding protein-2. In Model 2, only soluble CD40 ligand remained strongly associated with death/MI when all clinical risk predictors were retained. Model 3 identified a set of 6 biomarkers (intercellular adhesion molecule-1, matrix metalloproteinase-3, N-terminal pro-B-type natriuretic peptide, interleukin-6, soluble CD40 ligand, and insulin-like growth factor binding protein-2) and 5 clinical variables (age, red-cell distribution width, diabetes mellitus, hemoglobin, and New York Heart Association class) strongly associated with death/MI.Simultaneously assessing the association between multiple putative protein biomarkers of cardiovascular risk and clinical outcomes is useful in identifying relevant biomarker panels for further assessment.

Authors
Halim, SA; Neely, ML; Pieper, KS; Shah, SH; Kraus, WE; Hauser, ER; Califf, RM; Granger, CB; Newby, LK
MLA Citation
Halim, SA, Neely, ML, Pieper, KS, Shah, SH, Kraus, WE, Hauser, ER, Califf, RM, Granger, CB, and Newby, LK. "Simultaneous consideration of multiple candidate protein biomarkers for long-term risk for cardiovascular events." Circulation. Cardiovascular genetics 8.1 (February 2015): 168-177.
PMID
25422398
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
8
Issue
1
Publish Date
2015
Start Page
168
End Page
177
DOI
10.1161/circgenetics.113.000490

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.

Authors
Do, R; Stitziel, NO; Won, H-H; Jørgensen, AB; Duga, S; Angelica Merlini, P; Kiezun, A; Farrall, M; Goel, A; Zuk, O; Guella, I; Asselta, R; Lange, LA; Peloso, GM; Auer, PL; Girelli, D; Martinelli, N; Farlow, DN; DePristo, MA; Roberts, R; Stewart, AFR; Saleheen, D; Danesh, J; Epstein, SE; Sivapalaratnam, S; Hovingh, GK; Kastelein, JJ; Samani, NJ; Schunkert, H; Erdmann, J; Shah, SH; Kraus, WE; Davies, R; Nikpay, M; Johansen, CT; Wang, J; Hegele, RA; Hechter, E; Marz, W; Kleber, ME; Huang, J et al.
MLA Citation
Do, R, Stitziel, NO, Won, H-H, Jørgensen, AB, Duga, S, Angelica Merlini, P, Kiezun, A, Farrall, M, Goel, A, Zuk, O, Guella, I, Asselta, R, Lange, LA, Peloso, GM, Auer, PL, Girelli, D, Martinelli, N, Farlow, DN, DePristo, MA, Roberts, R, Stewart, AFR, Saleheen, D, Danesh, J, Epstein, SE, Sivapalaratnam, S, Hovingh, GK, Kastelein, JJ, Samani, NJ, Schunkert, H, Erdmann, J, Shah, SH, Kraus, WE, Davies, R, Nikpay, M, Johansen, CT, Wang, J, Hegele, RA, Hechter, E, Marz, W, Kleber, ME, and Huang, J et al. "Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction." Nature 518.7537 (February 2015): 102-106.
PMID
25487149
Source
epmc
Published In
Nature
Volume
518
Issue
7537
Publish Date
2015
Start Page
102
End Page
106
DOI
10.1038/nature13917

Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders.

Authors
Madden, L; Juhas, M; Kraus, WE; Truskey, GA; Bursac, N
MLA Citation
Madden, L, Juhas, M, Kraus, WE, Truskey, GA, and Bursac, N. "Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs." eLife 4 (January 9, 2015): e04885-.
Website
http://hdl.handle.net/10161/9364
PMID
25575180
Source
epmc
Published In
eLife
Volume
4
Publish Date
2015
Start Page
e04885
DOI
10.7554/elife.04885

Genetic variants associated with vein graft stenosis after coronary artery bypass grafting

© 2015 Forum Multimedia Publishing, LLC.Background: Vein graft stenosis after coronary artery bypass grafting (CABG) is common. Identifying genes associated with vein graft stenosis after CABG could reveal novel mechanisms of disease and discriminate patients at risk for graft failure. We hypothesized that genome-wide association would identify these genes. Methods: We performed a genome-wide association study on a subset of patients presenting for cardiac catheterization for concern of ischemic heart disease, who also underwent CABG and subsequent coronary angiography after CABG for clinical indications (n = 521). Cases were defined as individuals with ≥50% stenosis in any vein graft on any cardiac catheterization, and controls were defined as those who did not have vein graft stenosis on any subsequent cardiac catheterization. Multivariable logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) and vein graft stenosis. Results: Sixty-nine percent of patients had vein graft failure after CABG. Seven SNPs were significantly associated with vein graft stenosis, including intronic SNPs in the genes PALLD (Rs6854137, P = 3.77 × 10-6), ARID1B (Rs184074, P = 5.97 × 10-6), and TMEM123 (Rs11225247, P = 8.25 × 10-6); and intergenic SNPs near the genes ABCA13 (Rs10232860, P = 4.54 × 10-6), RMI2 (Rs9921338, P = 6.15 × 10-6), PRM2 (Rs7198849, P = 7.27 × 10-6), and TNFSF4 (Rs17346536, P = 9.33 × 10-6). Conclusions: We have identified novel genetic variants that may predispose to risk of vein graft failure after CABG, many within biologically plausible pathways. These polymorphisms merit further investigation, as they could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy.

Authors
Shah, AA; Haynes, C; Craig, DM; Sebek, J; Grass, E; Abramson, K; Hauser, ER; Gregory, SG; Kraus, WE; Smith, PK; Shah, SH
MLA Citation
Shah, AA, Haynes, C, Craig, DM, Sebek, J, Grass, E, Abramson, K, Hauser, ER, Gregory, SG, Kraus, WE, Smith, PK, and Shah, SH. "Genetic variants associated with vein graft stenosis after coronary artery bypass grafting." Heart Surgery Forum 18.1 (January 1, 2015): E1-E5.
Source
scopus
Published In
The heart surgery forum
Volume
18
Issue
1
Publish Date
2015
Start Page
E1
End Page
E5
DOI
10.1532/HSF98.2015489

Authorship in a multicenter clinical trial: The heart failure - A controlled trial investigating outcomes of exercise training (HF-ACTION) authorship and publication (HAP) scoring system results

© 2015 Elsevier Inc. All rights reserved.Background Few guidelines exist regarding authorship on manuscripts resulting from large multicenter trials. The HF-ACTION investigators devised a system to address assignment of authorship on trial publications and tested the outcomes in the course of conducting the large, multicenter, National Heart, Lung, and Blood Institute-funded trial (n = 2,331; 82 clinical sites; 3 countries). The HF-ACTION Authorship and Publication (HAP) scoring system was designed to enhance rate of dissemination, recognize investigator contributions to the successful conduct of the trial, and harness individual expertise in manuscript generation. Methods The HAP score was generated by assigning points based on investigators' participation in trial enrollment, follow-up, and adherence, as well as participation in committees and other trial activity. Overall publication rates, publication rates by author, publication rates by site, and correlation between site publication and HAP score using a Poisson regression model were examined. Results Fifty peer-reviewed, original manuscripts were published within 6.5 years after conclusion of study enrollment. In total, 137 different authors were named in at least 1 publication. Forty-five (55%) of the 82 sites had an author named to at least 1 article. A Poisson regression model examining incident rate ratios revealed that a higher HAP score resulted in a higher incidence of a manuscript, with a 100-point increase in site score corresponding to an approximately 32% increase in the incidence of a published article. Conclusions Given the success in publishing a large number of manuscripts and widely distributing authorship, regular use of a transparent, objective authorship assignment system for publishing results from multicenter trials may be recommended to optimize fairness and dissemination of trial results.

Authors
Whellan, DJ; Kraus, WE; Kitzman, DW; Rooney, B; Keteyian, SJ; Piña, IL; Ellis, SJ; Ghali, JK; Lee, KL; Cooper, LS; O'Connor, CM
MLA Citation
Whellan, DJ, Kraus, WE, Kitzman, DW, Rooney, B, Keteyian, SJ, Piña, IL, Ellis, SJ, Ghali, JK, Lee, KL, Cooper, LS, and O'Connor, CM. "Authorship in a multicenter clinical trial: The heart failure - A controlled trial investigating outcomes of exercise training (HF-ACTION) authorship and publication (HAP) scoring system results." American Heart Journal 169.4 (January 1, 2015): 457-463.e6.
Source
scopus
Published In
American Heart Journal
Volume
169
Issue
4
Publish Date
2015
Start Page
457
End Page
463.e6
DOI
10.1016/j.ahj.2014.11.022

Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene

© 2015 Macmillan Publishers Limited. All rights reserved.We performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps=7.14E-09 to 2.33E-08, uncorrected; Ps=1.99E-07 to 5.18E-07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps=0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate=0.26, P=0.033, 95% CI=0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate=0.004, P=0.34, 95% CI=-0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values=0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease.

Authors
Singh, A; Babyak, MA; Nolan, DK; Brummett, BH; Jiang, R; Siegler, IC; Kraus, WE; Shah, SH; Williams, RB; Hauser, ER
MLA Citation
Singh, A, Babyak, MA, Nolan, DK, Brummett, BH, Jiang, R, Siegler, IC, Kraus, WE, Shah, SH, Williams, RB, and Hauser, ER. "Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene." European Journal of Human Genetics 23.6 (January 1, 2015): 854-862.
Source
scopus
Published In
European Journal of Human Genetics
Volume
23
Issue
6
Publish Date
2015
Start Page
854
End Page
862
DOI
10.1038/ejhg.2014.189

Preventive cardiology: Counseling older at-risk adults on nutrition

© Springer Science+Business Media New York 2004, 2009, 2015.Preventive cardiology brings a detailed understanding of the interplay between known and emerging risk factors to the long-term treatment of cardiac patients particularly targeting cardiometabolic risk factors. In essence, it translates a growing scientific knowledge base into clinical practice. The discipline of preventive cardiology applies research in vascular biology, clinical genetics, cardiovascular epidemiology, clinical pharmacology, and clinical trials to practical prevention strategies for patients.

Authors
Kraus, WE; Pruitt, JD
MLA Citation
Kraus, WE, and Pruitt, JD. "Preventive cardiology: Counseling older at-risk adults on nutrition." Handbook of Clinical Nutrition and Aging, Third Edition. January 1, 2015. 203-214.
Source
scopus
Publish Date
2015
Start Page
203
End Page
214
DOI
10.1007/978-1-4939-1929-1_12

Exercise training and pacing status in patients with heart failure: results from HF-ACTION.

We sought to determine if outcomes with exercise training in heart failure (HF) vary according to ventricular pacing type.Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized 2,331 outpatients with HF and left ventricular ejection fraction ≤35% to usual care plus exercise training or usual care alone. We examined the relationship between outcomes and randomized treatment according to ventricular pacing status with the use of Cox proportional hazards modeling. In HF-ACTION 1,118 patients (48%) had an implanted cardiac rhythm device: 683 with right ventricular (RV) and 435 with biventricular (BiV) pacemakers. Patients with pacing devices were older, more frequently white, and had lower peak VO2 (P < .001 for all). Peak VO2 improved similarly with training in groups with and without pacing devices. The primary composite end point-all-cause death or hospitalization-was reduced only in patients randomized to exercise training without a device (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.67-0.93 [P = .004]; RV lead: HR 1.04, 95% CI 0.84-1.28 [P = .74]; BiV pacing: HR 1.05, 95% CI 0.82-1.34 [P = .72]; interaction P = .058).Exercise training may improve exercise capacity in patients with implanted cardiac devices. However, the apparent beneficial effects of exercise on hospitalization or death may be attenuated in patients with implanted cardiac devices and requires further study.

Authors
Zeitler, EP; Piccini, JP; Hellkamp, AS; Whellan, DJ; Jackson, KP; Ellis, SJ; Kraus, WE; Keteyian, SJ; Kitzman, DW; Ewald, GA; Fleg, JL; Piña, IL; O'Connor, CM
MLA Citation
Zeitler, EP, Piccini, JP, Hellkamp, AS, Whellan, DJ, Jackson, KP, Ellis, SJ, Kraus, WE, Keteyian, SJ, Kitzman, DW, Ewald, GA, Fleg, JL, Piña, IL, and O'Connor, CM. "Exercise training and pacing status in patients with heart failure: results from HF-ACTION." Journal of cardiac failure 21.1 (January 2015): 60-67.
PMID
25463413
Source
epmc
Published In
Journal of Cardiac Failure
Volume
21
Issue
1
Publish Date
2015
Start Page
60
End Page
67
DOI
10.1016/j.cardfail.2014.10.004

Exercise training as therapy for heart failure: current status and future directions.

Authors
Fleg, JL; Cooper, LS; Borlaug, BA; Haykowsky, MJ; Kraus, WE; Levine, BD; Pfeffer, MA; Piña, IL; Poole, DC; Reeves, GR; Whellan, DJ; Kitzman, DW
MLA Citation
Fleg, JL, Cooper, LS, Borlaug, BA, Haykowsky, MJ, Kraus, WE, Levine, BD, Pfeffer, MA, Piña, IL, Poole, DC, Reeves, GR, Whellan, DJ, and Kitzman, DW. "Exercise training as therapy for heart failure: current status and future directions." Circulation. Heart failure 8.1 (January 2015): 209-220. (Review)
PMID
25605639
Source
epmc
Published In
Circulation: Heart Failure
Volume
8
Issue
1
Publish Date
2015
Start Page
209
End Page
220
DOI
10.1161/circheartfailure.113.001420

Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis.

Until recently, reports of physical activity in rheumatoid arthritis (RA) were limited to self-report methods and/or leisure-time physical activity. Our objectives were to assess, determine correlates of, and compare to well-matched controls both exercise and sedentary time in a typical clinical cohort of RA.Persons with established RA (seropositive or radiographic erosions; n = 41) without diabetes or cardiovascular disease underwent assessments of traditional and disease-specific correlates of physical activity and 7 days of triaxial accelerometry. Twenty-seven age, gender, and body mass index (BMI)-matched controls were assessed.For persons with RA, objectively measured median (25th-75th percentile) exercise time was 3 (1-11) min/day; only 10% (n = 4) of participants exercised for ≥ 30 min/day. Time spent in sedentary activities was 92% (89-95%). Exercise time was not related to pain but was inversely related to disease activity (r = -0.3, p < 0.05) and disability (r = -0.3, p < 0.05) and positively related to self-efficacy for endurance activity (r = 0.4, p < 0.05). Sedentary activity was related only to self-efficacy for endurance activity (r = -0.4, p < 0.05). When compared to matched controls, persons with RA exhibited poorer self-efficacy for physical activity but similar amounts of exercise and sedentary time.For persons with RA and without diabetes or cardiovascular disease, time spent in exercise was well below established guidelines and activity patterns were predominantly sedentary. For optimal care in RA, in addition to promoting exercise, clinicians should consider assessing sedentary behaviour and self-efficacy for exercise. Future interventions might determine whether increased self-efficacy can increase physical activity in RA.

Authors
Huffman, KM; Pieper, CF; Hall, KS; St Clair, EW; Kraus, WE
MLA Citation
Huffman, KM, Pieper, CF, Hall, KS, St Clair, EW, and Kraus, WE. "Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis." Scandinavian journal of rheumatology 44.2 (January 2015): 106-110.
PMID
25222824
Source
epmc
Published In
Scandinavian Journal of Rheumatology (Informa)
Volume
44
Issue
2
Publish Date
2015
Start Page
106
End Page
110
DOI
10.3109/03009742.2014.931456

SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization.

SLCO1B1 variants are associated with intermediate outcomes that may increase risk of death/myocardial infarction (MI) in statin-treated patients.In high-risk Caucasians undergoing cardiac catheterization, we tested the association between rs4149056/625T>C and rs2306283/492A>G with low-density lipoprotein cholesterol (LDL-c) over 3 years (n = 1402) and death/MI over 6 years (n = 2994), accounting for statin use or type during follow-up.Carriers of the rs4149056 C allele had 6.2 ± 1.7 mg/dl higher LDL-c per C allele (p < 0.001) but were not at higher risk for death/MI (p = 0.9). We found no associations between rs2306283 and LDL-c or death/MI (p > 0.6).Functional SLCO1B1 variants are not associated with death/MI in patients commonly treated with statins, despite higher LDL-c in carriers of the rs4149056 C allele.

Authors
Li, JH; Suchindran, S; Shah, SH; Kraus, WE; Ginsburg, GS; Voora, D
MLA Citation
Li, JH, Suchindran, S, Shah, SH, Kraus, WE, Ginsburg, GS, and Voora, D. "SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization." Pharmacogenomics 16.5 (January 2015): 449-458.
PMID
25916517
Source
epmc
Published In
Pharmacogenomics
Volume
16
Issue
5
Publish Date
2015
Start Page
449
End Page
458
DOI
10.2217/pgs.15.2

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.

Homozygosity for a premature stop codon (X) in the ACTN3 "sprinter" gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.

Authors
Deschamps, CL; Connors, KE; Klein, MS; Johnsen, VL; Shearer, J; Vogel, HJ; Devaney, JM; Gordish-Dressman, H; Many, GM; Barfield, W; Hoffman, EP; Kraus, WE; Hittel, DS
MLA Citation
Deschamps, CL, Connors, KE, Klein, MS, Johnsen, VL, Shearer, J, Vogel, HJ, Devaney, JM, Gordish-Dressman, H, Many, GM, Barfield, W, Hoffman, EP, Kraus, WE, and Hittel, DS. "The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults." PloS one 10.6 (January 2015): e0130644-.
PMID
26107372
Source
epmc
Published In
PloS one
Volume
10
Issue
6
Publish Date
2015
Start Page
e0130644
DOI
10.1371/journal.pone.0130644

Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction.

Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI.A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status.In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04).A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection.

Authors
Rose, JJ; Voora, D; Cyr, DD; Lucas, JE; Zaas, AK; Woods, CW; Newby, LK; Kraus, WE; Ginsburg, GS
MLA Citation
Rose, JJ, Voora, D, Cyr, DD, Lucas, JE, Zaas, AK, Woods, CW, Newby, LK, Kraus, WE, and Ginsburg, GS. "Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction." PloS one 10.7 (January 2015): e0132259-.
Website
http://hdl.handle.net/10161/12503
PMID
26193668
Source
epmc
Published In
PloS one
Volume
10
Issue
7
Publish Date
2015
Start Page
e0132259
DOI
10.1371/journal.pone.0132259

Incremental and independent value of cardiopulmonary exercise test measures and the Seattle Heart Failure Model for prediction of risk in patients with heart failure

© 2015 International Society for Heart and Lung Transplantation.Background Multivariable risk scores and exercise measures are well-validated risk prediction methods. Combining information from a functional evaluation and a risk model may improve accuracy of risk predictions. We analyzed whether adding exercise measures to the Seattle Heart Failure Model (SHFM) improves risk prediction accuracy in systolic heart failure. Methods We used a sample of patients from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) study (http://www.clinicaltrials.gov; unique identifier: NCT00047437) to examine the addition of peak oxygen consumption, expired volume per unit time/volume of carbon dioxide slope, 6-minute walk distance, or cardiopulmonary exercise duration to the SHFM. Multivariable Cox proportional hazards models were used to test the association between the combined end point (death, left ventricular assist device, or cardiac transplantation) and the addition of exercise variables to the SHFM. Results The sample included 2,152 patients. The SHFM and all exercise measures were associated with events (all p < 0.0001) in proportional hazards models. There was statistically significant improvement in risk estimation when exercise measures were added to the SHFM. However, the improvement in the C index for the addition of peak volume of oxygen consumption (+0.01), expired volume per unit time/volume of carbon dioxide slope (+0.02), 6-minute walk distance (-0.001), and cardiopulmonary exercise duration (+0.001) to the SHFM was small or slightly worse than the SHFM alone. Changes in risk assignment with the addition of exercise variables were minimal for patients above or below a 15% 1-year mortality. Conclusions Exercise performance measures and the SHFM are independently useful for predicting risk in systolic heart failure. Adding cardiopulmonary exercise testing measures and 6MWD to the SHFM offers only minimal improvement in risk reassignment at clinically meaningful cut points.

Authors
Dardas, T; Li, Y; Reed, SD; O'Connor, CM; Whellan, DJ; Ellis, SJ; Schulman, KA; Kraus, WE; Forman, DE; Levy, WC
MLA Citation
Dardas, T, Li, Y, Reed, SD, O'Connor, CM, Whellan, DJ, Ellis, SJ, Schulman, KA, Kraus, WE, Forman, DE, and Levy, WC. "Incremental and independent value of cardiopulmonary exercise test measures and the Seattle Heart Failure Model for prediction of risk in patients with heart failure." Journal of Heart and Lung Transplantation 34.8 (2015): 1017-1023.
Source
scival
Published In
The Journal of Heart and Lung Transplantation
Volume
34
Issue
8
Publish Date
2015
Start Page
1017
End Page
1023
DOI
10.1016/j.healun.2015.03.017

Change in levels of physical activity after diagnosis of type 2 diabetes: an observational analysis from the NAVIGATOR study.

Increased physical activity is known to be beneficial in people with type 2 diabetes mellitus (T2DM), but it is not known whether individuals change their activity levels after T2DM diagnosis. The present Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, conducted in participants with impaired glucose tolerance at high cardiovascular risk, assessed ambulatory activity annually using research-grade pedometers. Oral glucose tolerance tests were performed annually and repeated to confirm T2DM diagnosis. This observational analysis used general linear models to compare step counts before and after T2DM diagnosis in the 2816 participants with the requisite data. Participants were relatively inactive at baseline, taking a median (interquartile range) of 5488 (3258-8361) steps/day, which decreased after T2DM diagnosis by a mean (s.e.) of 258 (64) steps/day (p < 0.0001); however, after adjusting for background trend for activity, step count after T2DM diagnosis was unchanged [mean (s.e.) of 103 (87) fewer steps/day; p = 0.23]. Awareness of T2DM diagnosis had no impact on the trajectory of activity established before the diagnosis.

Authors
Preiss, D; Haffner, SM; Thomas, LE; Sun, J-L; Sattar, N; Yates, T; J Davies, M; McMurray, JJ; Holman, RR; Califf, RM; Kraus, WE
MLA Citation
Preiss, D, Haffner, SM, Thomas, LE, Sun, J-L, Sattar, N, Yates, T, J Davies, M, McMurray, JJ, Holman, RR, Califf, RM, and Kraus, WE. "Change in levels of physical activity after diagnosis of type 2 diabetes: an observational analysis from the NAVIGATOR study." Diabetes, obesity & metabolism 16.12 (December 2014): 1265-1268.
PMID
24861892
Source
epmc
Published In
Diabetes Obesity & Metabolism
Volume
16
Issue
12
Publish Date
2014
Start Page
1265
End Page
1268
DOI
10.1111/dom.12320

Aspirin-Responsive Platelet Genes Are Associated With Platelet Function and Cardiovascular Events

Authors
Suchindran, S; Himmel, T; Ortel, TL; Becker, RC; Kraus, WE; Newby, LK; Ginsburg, GS; Voora, D
MLA Citation
Suchindran, S, Himmel, T, Ortel, TL, Becker, RC, Kraus, WE, Newby, LK, Ginsburg, GS, and Voora, D. "Aspirin-Responsive Platelet Genes Are Associated With Platelet Function and Cardiovascular Events." CIRCULATION 130 (November 25, 2014).
Source
wos-lite
Published In
Circulation
Volume
130
Publish Date
2014

Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.

Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms.Subjects at risk of metabolic disease were randomised to 6 months of inactivity or one of five aerobic and/or resistance training programmes (n = 112). Pre/post-intervention assessments included cardiorespiratory fitness ([Formula: see text]), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism.Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of even-chain acylcarnitines (median 37-488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in [Formula: see text], TGs and SI (R = 0.20-0.31, p < 0.05). Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R = 0.39 and 0.24, p < 0.05) emerged as the strongest correlates of SI.The metabolic signatures of exercise-trained skeletal muscle reflected reprogramming of mitochondrial function and intermediary metabolism and correlated with changes in cardiometabolic fitness. Succinate metabolism and the succinate dehydrogenase complex emerged as a potential regulatory node that intersects with whole-body insulin sensitivity. This study identifies new avenues for mechanistic research aimed at understanding the health benefits of physical activity. Trial registration ClinicalTrials.gov NCT00200993 and NCT00275145 Funding This work was supported by the National Heart, Lung, and Blood Institute (National Institutes of Health), National Institute on Aging (National Institutes of Health) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health).

Authors
Huffman, KM; Koves, TR; Hubal, MJ; Abouassi, H; Beri, N; Bateman, LA; Stevens, RD; Ilkayeva, OR; Hoffman, EP; Muoio, DM; Kraus, WE
MLA Citation
Huffman, KM, Koves, TR, Hubal, MJ, Abouassi, H, Beri, N, Bateman, LA, Stevens, RD, Ilkayeva, OR, Hoffman, EP, Muoio, DM, and Kraus, WE. "Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness." Diabetologia 57.11 (November 2014): 2282-2295.
PMID
25091629
Source
epmc
Published In
Diabetologia
Volume
57
Issue
11
Publish Date
2014
Start Page
2282
End Page
2295
DOI
10.1007/s00125-014-3343-4

Pilot study: incorporation of pharmacogenetic testing in medication therapy management services.

Aim: To describe the rationale and design of a pilot study evaluating the integration of pharmacogenetic (PGx) testing into pharmacist-delivered medication therapy management (MTM). Study rationale: Clinical delivery approaches of PGx testing involving pharmacists may overcome barriers of limited physician knowledge about and experience with testing. Study design: We will assess the addition of PGx testing to MTM services for cardiology patients taking three or more medications including simvastatin or clopidogrel. We will measure the impact of MTM plus PGx testing on drug/dose adjustment and clinical outcomes. Factors associated with delivery, such as time to prepare and conduct MTM and consult with physicians will be recorded. Additionally, patient interest and satisfaction will be measured. Anticipated results: We anticipate that PGx testing can be practically integrated into standard a MTM service, providing a viable delivery model for testing. Conclusion: Given the lack of evidence of an effective PGx delivery models, this study will provide preliminary evidence regarding a pharmacist-delivered approach.

Authors
Haga, SB; Allen LaPointe, NM; Moaddeb, J; Mills, R; Patel, M; Kraus, WE
MLA Citation
Haga, SB, Allen LaPointe, NM, Moaddeb, J, Mills, R, Patel, M, and Kraus, WE. "Pilot study: incorporation of pharmacogenetic testing in medication therapy management services." Pharmacogenomics 15.14 (November 2014): 1729-1737.
PMID
25493566
Source
epmc
Published In
Pharmacogenomics
Volume
15
Issue
14
Publish Date
2014
Start Page
1729
End Page
1737

Adipose depots, not disease-related factors, account for skeletal muscle insulin sensitivity in established and treated rheumatoid arthritis.

In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity.Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference.Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SI geometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10(-5) min(-1)/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use.In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.

Authors
AbouAssi, H; Tune, KN; Gilmore, B; Bateman, LA; McDaniel, G; Muehlbauer, M; Huebner, JL; Hoenig, HM; Kraus, VB; St Clair, EW; Kraus, WE; Huffman, KM
MLA Citation
AbouAssi, H, Tune, KN, Gilmore, B, Bateman, LA, McDaniel, G, Muehlbauer, M, Huebner, JL, Hoenig, HM, Kraus, VB, St Clair, EW, Kraus, WE, and Huffman, KM. "Adipose depots, not disease-related factors, account for skeletal muscle insulin sensitivity in established and treated rheumatoid arthritis." The Journal of rheumatology 41.10 (October 2014): 1974-1979.
PMID
24986846
Source
epmc
Published In
The Journal of rheumatology
Volume
41
Issue
10
Publish Date
2014
Start Page
1974
End Page
1979
DOI
10.3899/jrheum.140224

G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.

We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass grafting and were treated with perioperative β-blockers (BBs).Two cohorts of patients who underwent coronary artery bypass grafting and received perioperative BBs at Duke University Medical Center were studied. In a discovery cohort of 563 individuals from the Perioperative Genetics and Safety Outcomes Study (PEGASUS), using a covariate-adjusted logistic regression analysis, we tested 492 single-nucleotide polymorphisms (SNPs) in 10 candidate genes of the adrenergic signaling pathway and cytochrome P450 2D6 for association with postoperative AF despite perioperative BB therapy. SNPs meeting a false discovery rate ≤0.20 (P<0.002) were then tested in the replication cohort of 245 individuals from the Catheterization Genetics biorepository. Of the 492 SNPs examined, 4 intronic SNPs of the G protein-coupled kinase 5 (GRK5) gene were significantly associated with postoperative AF despite perioperative BB therapy in the discovery cohort with additive odds ratios between 1.72 and 2.75 (P=4.78×10(-5) to 0.0015). Three of these SNPs met nominal significance levels in the replication cohort with odds ratios between 2.07 and 2.60 (P=0.007 to 0.016). However, meta-analysis of the 2 data sets cohorts suggested strong association with postoperative AF despite perioperative BB therapy in all 4 SNPs (meta-P values from 1.66×10(-6) to 3.39×10(-5)).In patients undergoing coronary artery bypass grafting, genetic variation in GRK5 is associated with postoperative AF despite perioperative BB therapy.

Authors
Kertai, MD; Li, Y-W; Li, Y-J; Shah, SH; Kraus, WE; Fontes, ML; Stafford-Smith, M; Newman, MF; Podgoreanu, MV; Mathew, JP
MLA Citation
Kertai, MD, Li, Y-W, Li, Y-J, Shah, SH, Kraus, WE, Fontes, ML, Stafford-Smith, M, Newman, MF, Podgoreanu, MV, and Mathew, JP. "G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers." Circulation. Cardiovascular genetics 7.5 (October 2014): 625-633.
PMID
25049040
Source
epmc
Published In
Circulation: Cardiovascular Genetics
Volume
7
Issue
5
Publish Date
2014
Start Page
625
End Page
633
DOI
10.1161/circgenetics.113.000451

Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies.

A gene expression score (GES) for obstructive coronary artery disease (CAD) has been validated in two multicenter studies. Receiver-operating characteristics (ROC) analysis of the GES on an expanded Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD defined by quantitative coronary angiography (QCA) or clinical reads yielded similar performance (area under the curve (AUC)=0.70, N=1,502) to the original validation cohort (AUC=0.70, N=526). Analysis of 138 non-Caucasian and 1,364 Caucasian patients showed very similar performance (AUCs=0.72 vs. 0.70). To assess analytic stability, stored samples of the original validation cohort (N=526) was re-tested after 5 years, and the mean score changed from 20.3 to 19.8 after 5 years (N=501, 95 %). To assess patient scores over time, GES was determined on samples from 173 Coronary Obstruction Detection by Molecular Personalized Gene Expression (COMPASS) study (NCT no. 01117506) patients at approximately 1 year post-enrollment. Mean scores increased slightly from 15.9 to 17.3, corresponding to a 2.5 % increase in obstructive CAD likelihood. Changes in cardiovascular medications did not show a significant change in GES.

Authors
Daniels, SE; Beineke, P; Rhees, B; McPherson, JA; Kraus, WE; Thomas, GS; Rosenberg, S
MLA Citation
Daniels, SE, Beineke, P, Rhees, B, McPherson, JA, Kraus, WE, Thomas, GS, and Rosenberg, S. "Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies." Journal of cardiovascular translational research 7.7 (October 2014): 615-622.
PMID
25119856
Source
epmc
Published In
Journal of Cardiovascular Translational Research
Volume
7
Issue
7
Publish Date
2014
Start Page
615
End Page
622
DOI
10.1007/s12265-014-9583-3

Safety and efficacy of aerobic training in patients with cancer who have heart failure: an analysis of the HF-ACTION randomized trial.

To investigate the efficacy and safety of aerobic training (AT) in patients with cancer with medically stable heart failure (HF).A retrospective analysis of 90 patients with cancer who have HF and who were randomly assigned to AT (n = 47) or guideline-based usual care (UC; n = 43) was performed. AT consisted of three supervised sessions per week at 20 to 45 minutes per session at 60% to 70% of heart rate reserve for 12 weeks followed by home-based sessions for 4 to 12 months. The primary end point was all-cause mortality and hospitalization. Secondary end points were other clinical events, safety, and change in exercise capacity (VO(2peak)) and health-related quality of life (HRQOL).Median follow-up was 35 months. In intention-to-treat (ITT) analyses, all-cause mortality or hospitalization at 2 years was 74% in the AT group compared with 67% in the UC group (adjusted hazard ratio [HR], 1.11; 95% CI, 0.69 to 1.77; P = .676). The incidence of cardiovascular mortality or cardiovascular hospitalization was significantly higher in the AT group compared with the UC group (41% v 67%; adjusted HR, 1.94; 95% CI, 1.12 to 3.16; P = .017). There were no differences in any VO(2peak) or HRQOL end points. In post hoc analyses based on adherence to AT, all-cause mortality and hospitalization was 66% in adherent patients (≥ 90 minutes per week) compared with 84% in nonadherent patients (< 90 minutes per week).In ITT analyses, AT did not improve clinical outcomes in patients with cancer who had HF. Post hoc analyses suggested that patients not capable of adhering to the planned AT prescription may be at increased risk of clinical events.

Authors
Jones, LW; Douglas, PS; Khouri, MG; Mackey, JR; Wojdyla, D; Kraus, WE; Whellan, DJ; O'Connor, CM
MLA Citation
Jones, LW, Douglas, PS, Khouri, MG, Mackey, JR, Wojdyla, D, Kraus, WE, Whellan, DJ, and O'Connor, CM. "Safety and efficacy of aerobic training in patients with cancer who have heart failure: an analysis of the HF-ACTION randomized trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32.23 (August 2014): 2496-2502.
PMID
25002717
Source
epmc
Published In
Journal of Clinical Oncology
Volume
32
Issue
23
Publish Date
2014
Start Page
2496
End Page
2502
DOI
10.1200/jco.2013.53.5724

Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure.

The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure.The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown.HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP.After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure.Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.

Authors
Ahmad, T; Fiuzat, M; Neely, B; Neely, ML; Pencina, MJ; Kraus, WE; Zannad, F; Whellan, DJ; Donahue, MP; Piña, IL; Adams, KF; Kitzman, DW; O'Connor, CM; Felker, GM
MLA Citation
Ahmad, T, Fiuzat, M, Neely, B, Neely, ML, Pencina, MJ, Kraus, WE, Zannad, F, Whellan, DJ, Donahue, MP, Piña, IL, Adams, KF, Kitzman, DW, O'Connor, CM, and Felker, GM. "Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure." JACC. Heart failure 2.3 (June 2014): 260-268.
PMID
24952693
Source
epmc
Published In
JACC: Heart Failure
Volume
2
Issue
3
Publish Date
2014
Start Page
260
End Page
268
DOI
10.1016/j.jchf.2013.12.004

The doubly labeled water method produces highly reproducible longitudinal results in nutrition studies.

The doubly labeled water (DLW) method is considered the reference method for the measurement of energy expenditure under free-living conditions. However, the reproducibility of the DLW method in longitudinal studies is not well documented. This study was designed to evaluate the longitudinal reproducibility of the DLW method using 2 protocols developed and implemented in a multicenter clinical trial-the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). To document the longitudinal reproducibility of the DLW method, 2 protocols, 1 based on repeated analysis of dose dilutions over the course of the clinical trial (dose-dilution protocol) and 1 based on repeated but blinded analysis of randomly selected DLW studies (test-retest protocol), were carried out. The dose-dilution protocol showed that the theoretical fractional turnover rates for (2)H and (18)O and the difference between the 2 fractional turnover rates were reproducible to within 1% and 5%, respectively, over 4.5 y. The Bland-Altman pair-wise comparisons of the results generated from 50 test-retest DLW studies showed that the fractional turnover rates and isotope dilution spaces for (2)H and (18)O, and total energy expenditure, were highly reproducible over 2.4 y. Our results show that the DLW method is reproducible in longitudinal studies and confirm the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5-4.4 y. The 2 protocols can be adopted by other laboratories to document the longitudinal reproducibility of their measurements to ensure the long-term outcomes of interest are meaningful biologically. This trial was registered at clinicaltrials.gov as NCT00427193.

Authors
Wong, WW; Roberts, SB; Racette, SB; Das, SK; Redman, LM; Rochon, J; Bhapkar, MV; Clarke, LL; Kraus, WE
MLA Citation
Wong, WW, Roberts, SB, Racette, SB, Das, SK, Redman, LM, Rochon, J, Bhapkar, MV, Clarke, LL, and Kraus, WE. "The doubly labeled water method produces highly reproducible longitudinal results in nutrition studies." The Journal of nutrition 144.5 (May 2014): 777-783.
PMID
24523488
Source
epmc
Published In
The Journal of nutrition
Volume
144
Issue
5
Publish Date
2014
Start Page
777
End Page
783
DOI
10.3945/jn.113.187823

Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe exercise intolerance, and its pathophysiology is poorly understood. To determine whether skeletal muscle abnormalities contribute to their severely reduced peak exercise O2 consumption (Vo2), we examined 22 older HFPEF patients (70 ± 7 yr) compared with 43 age-matched healthy control (HC) subjects using needle biopsy of the vastus lateralis muscle and cardiopulmonary exercise testing to assess muscle fiber type distribution and capillarity and peak Vo2. In HFPEF versus HC patients, peak Vo2 (14.7 ± 2.1 vs. 22.9 ± 6.6 ml·kg(-1)·min(-1), P < 0.001) and 6-min walk distance (454 ± 72 vs. 573 ± 71 m, P < 0.001) were reduced. In HFPEF versus HC patients, the percentage of type I fibers (39.0 ± 11.4% vs. 53.7 ± 12.4%, P < 0.001), type I-to-type II fiber ratio (0.72 ± 0.39 vs. 1.36 ± 0.85, P = 0.001), and capillary-to-fiber ratio (1.35 ± 0.32 vs. 2.53 ± 1.37, P = 0.006) were reduced, whereas the percentage of type II fibers was greater (61 ± 11.4% vs. 46.3 ± 12.4%, P < 0.001). In univariate analyses, the percentage of type I fibers (r = 0.39, P = 0.003), type I-to-type II fiber ratio (r = 0.33, P = 0.02), and capillary-to-fiber ratio (r = 0.59, P < 0.0001) were positively related to peak Vo2. In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak Vo2. We conclude that older HFPEF patients have significant abnormalities in skeletal muscle, characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio, and these may contribute to their severe exercise intolerance. This suggests potential new therapeutic targets in this difficult to treat disorder.

Authors
Kitzman, DW; Nicklas, B; Kraus, WE; Lyles, MF; Eggebeen, J; Morgan, TM; Haykowsky, M
MLA Citation
Kitzman, DW, Nicklas, B, Kraus, WE, Lyles, MF, Eggebeen, J, Morgan, TM, and Haykowsky, M. "Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction." American journal of physiology. Heart and circulatory physiology 306.9 (May 2014): H1364-H1370.
PMID
24658015
Source
epmc
Published In
American journal of physiology. Heart and circulatory physiology
Volume
306
Issue
9
Publish Date
2014
Start Page
H1364
End Page
H1370
DOI
10.1152/ajpheart.00004.2014

Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: results from NAVIGATOR.

The cardiometabolic risk cluster metabolic syndrome (MS) includes ≥3 of elevated fasting glucose, hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-c), and increased waist circumference. Each can be affected by physical activity and diet. Our objective was to determine whether determine whether baseline physical activity and/or diet behavior impact MS in the course of a large pharmaceutical trial.This was an observational study from NAVIGATOR, a double-blind, randomized (nateglinide, valsartan, both, or placebo), controlled trial between 2002 and 2004. We studied data from persons (n=9306) with impaired glucose tolerance and cardiovascular disease (CVD) or CVD risk factors; 7118 with pedometer data were included in this analysis. Physical activity was assessed with 7-day pedometer records; diet behavior was self-reported on a 6-item survey. An MS score (MSSc) was calculated using the sum of each MS component, centered around the Adult Treatment Panel III threshold, and standardized according to sample standard deviation. Excepting HDL-c, assessed at baseline and year 3, MS components were assessed yearly. Follow-up averaged 6 years.For every 2000-step increase in average daily steps, there was an associated reduction in average MSSc of 0.29 (95% CI (-)0.33 to (-)0.25). For each diet behavior endorsed, there was an associated reduction in average MSSc of 0.05 (95% CI (-)0.08 to (-)0.01). Accounting for the effects of pedometer steps and diet behavior together had minimal impact on parameter estimates with no significant interaction. Relations were independent of age, sex, race, region, smoking, family history of diabetes, and use of nateglinide, valsartan, aspirin, antihypertensive, and lipid-lowering agent.Baseline physical activity and diet behavior were associated independently with reductions in MSSc such that increased attention to these lifestyle elements provides cardiometabolic benefits. Thus, given the potential to impact outcomes, assessment of physical activity and diet should be performed in pharmacologic trials targeting cardiometabolic risk.

Authors
Huffman, KM; Sun, J-L; Thomas, L; Bales, CW; Califf, RM; Yates, T; Davies, MJ; Holman, RR; McMurray, JJV; Bethel, MA; Tuomilehto, J; Haffner, SM; Kraus, WE
MLA Citation
Huffman, KM, Sun, J-L, Thomas, L, Bales, CW, Califf, RM, Yates, T, Davies, MJ, Holman, RR, McMurray, JJV, Bethel, MA, Tuomilehto, J, Haffner, SM, and Kraus, WE. "Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: results from NAVIGATOR." Metabolism: clinical and experimental 63.4 (April 2014): 554-561.
PMID
24559843
Source
epmc
Published In
Metabolism
Volume
63
Issue
4
Publish Date
2014
Start Page
554
End Page
561
DOI
10.1016/j.metabol.2014.01.002

Genetically guided statin therapy on statin perceptions, adherence, and cholesterol lowering: a pilot implementation study in primary care patients.

Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 genotype guided statin therapy (GGST) are unknown. Primary care patients (n = 58) who were nonadherent to statins and their providers received SLCO1B1*5 genotyping and guided recommendations via the electronic medical record (EMR). The primary outcome was the change in Beliefs about Medications Questionnaire, which measured patients' perceived needs for statins and concerns about adverse effects, measured before and after SLCO1B1*5 results. Concurrent controls (n = 59) were identified through the EMR to compare secondary outcomes: new statin prescriptions, statin utilization, and change in LDL-cholesterol (LDL-c). GGST patients had trends (p = 0.2) towards improved statin necessity and concerns. The largest changes were the "need for statin to prevent sickness" (p < 0.001) and "concern for statin to disrupt life" (p = 0.006). GGST patients had more statin prescriptions (p < 0.001), higher statin use (p < 0.001), and greater decrease in LDL-c (p = 0.059) during follow-up. EMR delivery of SLCO1B1*5 results and recommendations is feasible in the primary care setting. This novel intervention may improve patients' perceptions of statins and physician behaviors that promote higher statin adherence and lower LDL-c.

Authors
Li, JH; Joy, SV; Haga, SB; Orlando, LA; Kraus, WE; Ginsburg, GS; Voora, D
MLA Citation
Li, JH, Joy, SV, Haga, SB, Orlando, LA, Kraus, WE, Ginsburg, GS, and Voora, D. "Genetically guided statin therapy on statin perceptions, adherence, and cholesterol lowering: a pilot implementation study in primary care patients." Journal of personalized medicine 4.2 (March 27, 2014): 147-162.
PMID
25563221
Source
epmc
Published In
Journal of Personalized Medicine
Volume
4
Issue
2
Publish Date
2014
Start Page
147
End Page
162
DOI
10.3390/jpm4020147

Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis.

BACKGROUND: The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain. We investigated whether baseline and change in objectively-assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance. METHODS: We assessed prospective data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January, 2002, and January, 2004. Participants also either had existing cardiovascular disease (if age ≥50 years) or at least one additional cardiovascular risk factor (if age ≥55 years). Participants were followed-up for cardiovascular events (defined as cardiovascular mortality, non-fatal stroke, or myocardial infarction) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months. Adjusted Cox proportional hazard models quantified the association of baseline and change in ambulatory activity (from baseline to 12 months) with the risk of a subsequent cardiovascular event, after adjustment for each other and potential confounding variables. This study is registered with ClinicalTrials.govNCT00097786. FINDINGS: During 45,211 person-years follow-up, 531 cardiovascular events occurred. Baseline ambulatory activity (hazard ratio [HR] per 2000 steps per day 0·90, 95% CI 0·84-0·96) and change in ambulatory activity (0·92, 0·86-0·99) were inversely associated with the risk of a cardiovascular event. Results for change in ambulatory activity were unaffected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months. INTERPRETATION: In individuals at high cardiovascular risk with impaired glucose tolerance, both baseline levels of daily ambulatory activity and change in ambulatory activity display a graded inverse association with the subsequent risk of a cardiovascular event. FUNDING: Novartis Pharmaceuticals.

Authors
Yates, T; Haffner, SM; Schulte, PJ; Thomas, L; Huffman, KM; Bales, CW; Califf, RM; Holman, RR; McMurray, JJV; Bethel, MA; Tuomilehto, J; Davies, MJ; Kraus, WE
MLA Citation
Yates, T, Haffner, SM, Schulte, PJ, Thomas, L, Huffman, KM, Bales, CW, Califf, RM, Holman, RR, McMurray, JJV, Bethel, MA, Tuomilehto, J, Davies, MJ, and Kraus, WE. "Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis." Lancet 383.9922 (March 22, 2014): 1059-1066.
PMID
24361242
Source
pubmed
Published In
The Lancet
Volume
383
Issue
9922
Publish Date
2014
Start Page
1059
End Page
1066
DOI
10.1016/S0140-6736(13)62061-9

Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training

Aims To determine if type 2 diabetes mellitus (T2D) differentiates endothelial function and plasma nitrite response (a marker of nitric oxide bioavailability) during exercise in peripheral arterial disease (PAD) subjects prior to and following 3 months supervised exercise training (SET). Methods In subjects with T2D + PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using brachial artery flow-mediated dilation. On a separate day, venous blood draws were performed at rest and 10 min following a symptom-limited graded treadmill test (SL-GXT). Plasma samples were snap-frozen for analysis of nitrite by reductive chemiluminescence. All testing was repeated following 3 months of SET. Results Prior to training both groups demonstrated endothelial dysfunction, which was correlated with a net decrease in plasma nitrite following a SL-GXT (p ≤ 0.05). Following SET, the PAD-only group demonstrated an improvement in endothelial function (p ≤ 0.05) and COT (p ≤ 0.05), which was related to a net increase in plasma nitrite following the SL-GXT (both p ≤ 0.05). The T2D + PAD group had none of these increases. Conclusions T2D in the presence of PAD attenuated improvements in endothelial function, net plasma nitrite, and COT following SET. This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET. © 2014 Elsevier Inc. All rights reserved.

Authors
Allen, JD; Stabler, T; Kenjale, AA; Ham, KL; Robbins, JL; Duscha, BD; Kraus, WE; Annex, BH
MLA Citation
Allen, JD, Stabler, T, Kenjale, AA, Ham, KL, Robbins, JL, Duscha, BD, Kraus, WE, and Annex, BH. "Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training." Journal of Diabetes and its Complications 28.2 (March 1, 2014): 219-225.
Source
scopus
Published In
Journal of Diabetes and its Complications
Volume
28
Issue
2
Publish Date
2014
Start Page
219
End Page
225
DOI
10.1016/j.jdiacomp.2013.08.002

Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro.

Conditions under which skeletal myoblasts are cultured in vitro are critical to growth and differentiation of these cells into mature skeletal myofibers. We examined several culture conditions that promoted human skeletal myoblast (HSkM) culture and examined the effect of microRNAs and mechanical stimulation on differentiation. Culture conditions for HSkM are different from those that enable rapid C2C12 myoblast differentiation. Culture on a growth factor-reduced Matrigel (GFR-MG)-coated surface in 2% equine serum-supplemented differentiation medium to promote HSkM differentiation under static conditions was compared with culture conditions used for C2C12 cell differentiation. Such conditions led to a >20-fold increase in myogenic miR-1, miR-133a, and miR-206 expression, a >2-fold increase in myogenic transcription factor Mef-2C expression, and an increase in sarcomeric α-actinin protein. Imposing ±10% cyclic stretch at 0.5 Hz for 1 h followed by 5 h of rest over 2 wk produced a >20% increase in miR-1, miR-133a, and miR-206 expression in 8% equine serum and a >35% decrease in 2% equine serum relative to static conditions. HSkM differentiation was accelerated in vitro by inhibition of proliferation-promoting miR-133a: immunofluorescence for sarcomeric α-actinin exhibited accelerated development of striations compared with the corresponding negative control, and Western blotting showed 30% more α-actinin at day 6 postdifferentiation. This study showed that 100 μg/ml GFR-MG coating and 2% equine serum-supplemented differentiation medium enhanced HSkM differentiation and myogenic miR expression and that addition of antisense miR-133a alone can accelerate primary human skeletal muscle differentiation in vitro.

Authors
Cheng, CS; El-Abd, Y; Bui, K; Hyun, Y-E; Hughes, RH; Kraus, WE; Truskey, GA
MLA Citation
Cheng, CS, El-Abd, Y, Bui, K, Hyun, Y-E, Hughes, RH, Kraus, WE, and Truskey, GA. "Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro." Am J Physiol Cell Physiol 306.4 (February 15, 2014): C385-C395.
PMID
24336652
Source
pubmed
Published In
American journal of physiology. Cell physiology
Volume
306
Issue
4
Publish Date
2014
Start Page
C385
End Page
C395
DOI
10.1152/ajpcell.00179.2013

The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure

Background Exercise training is recommended for chronic heart failure (HF) patients to improve functional status and reduce risk of adverse outcomes. Elevated plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T (cTnT) are associated with increased risk of adverse outcomes in this patient population. Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear. Methods and Results Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study, a randomized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction (<35%). Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value, treatment assignment (exercise training vs usual care), and volume of exercise. Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption (peak VO2), hospitalizations, and mortality. Exercise training was not associated with significant changes in levels of NT-proBNP (P =.10), hs-CRP (P =.80), or detectable cTnT levels (P =.83) at 3 months. Controlling for baseline biomarker levels or volume of exercise did not alter these findings. Decreases in plasma concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with increases in peak VO2 (P <.001) at 3 months and decreased risk of hospitalizations or mortality (P ≤.04), even after adjustment for a comprehensive set of known predictors. Conclusions Exercise training did not lead to meaningful changes in biomarkers of myocardial stress, inflammation, or necrosis in patients with chronic HF. Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events. © 2014 Mosby, Inc.

Authors
Ahmad, T; Fiuzat, M; Mark, DB; Neely, B; Neely, M; Kraus, WE; Kitzman, DW; Whellan, DJ; Donahue, M; Zannad, F; Piña, IL; Adams, K; O'Connor, CM; Felker, GM
MLA Citation
Ahmad, T, Fiuzat, M, Mark, DB, Neely, B, Neely, M, Kraus, WE, Kitzman, DW, Whellan, DJ, Donahue, M, Zannad, F, Piña, IL, Adams, K, O'Connor, CM, and Felker, GM. "The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure." American Heart Journal 167.2 (February 1, 2014).
Source
scopus
Published In
American Heart Journal
Volume
167
Issue
2
Publish Date
2014
DOI
10.1016/j.ahj.2013.10.018

Are there negative responders to exercise training among heart failure patients?

Purpose: Aerobic exercise training has been used in patients with stable heart failure (HF) to reduce the risk of clinical events. However, due to patient heterogeneity, some patients may experience a decrease in functional capacity due to such training. The purpose of this study was to estimate the proportion of HF patients participating in a training program who had negative responses to such therapy and to compare them with a concurrent control group. Methods: Baseline and 3-month peak VO2 measurements were obtained on 1870 HF subjects who were randomized to receive either an exercise training program or a control program of usual care without exercise training. The exercise program consisted of supervised walking or stationary cycling 3 d·wk-1 for 12 wk as well as a 2-d·wk-1 home exercise program after completing 18 supervised sessions. A negative response was defined as a baseline-to-3-month decrease in peak VO2 of at least 5 mL·kg-1min-1, which was two times the SD of the control group's change in peak VO2. Results: The mean ±SD change in peak VO2 in the exercise group and control group was 0.8 ± 2.5 mL·kg-1min-1 and 0.2 ± 2.5 mL·kg-1min-1, respectively (P < 0.001). The percentage of negative responders in the exercise and control groups was 0.9% and 2.3% (P = 0.02). Conclusions: The low negative response rate in the exercise group combined with the slightly higher rate in the control group and equal variability in the exercise and control groups suggests that few if any subjects had training-related negative peak VO2 responses. These findings support current exercise recommendations for HF patients. Copyright © 2013 by the American College of Sports Medicine.

Authors
Leifer, ES; Brawner, CA; Fleg, JL; Kraus, WE; Whellan, DJ; Piña, IL; Keteyian, SJ
MLA Citation
Leifer, ES, Brawner, CA, Fleg, JL, Kraus, WE, Whellan, DJ, Piña, IL, and Keteyian, SJ. "Are there negative responders to exercise training among heart failure patients?." Medicine and Science in Sports and Exercise 46.2 (February 1, 2014): 219-224.
Source
scopus
Published In
Medicine and Science in Sports and Exercise
Volume
46
Issue
2
Publish Date
2014
Start Page
219
End Page
224
DOI
10.1249/MSS.0b013e3182a44164

Exercise biology and medicine: innovative research to improve global health.

Authors
Bamman, MM; Cooper, DM; Booth, FW; Chin, ER; Neufer, PD; Trappe, S; Lightfoot, JT; Kraus, WE; Joyner, MJ
MLA Citation
Bamman, MM, Cooper, DM, Booth, FW, Chin, ER, Neufer, PD, Trappe, S, Lightfoot, JT, Kraus, WE, and Joyner, MJ. "Exercise biology and medicine: innovative research to improve global health." Mayo Clinic proceedings 89.2 (February 2014): 148-153.
PMID
24485128
Source
epmc
Published In
Mayo Clinic Proceedings
Volume
89
Issue
2
Publish Date
2014
Start Page
148
End Page
153
DOI
10.1016/j.mayocp.2013.11.013

Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.

Authors
Peloso, GM; Auer, PL; Bis, JC; Voorman, A; Morrison, AC; Stitziel, NO; Brody, JA; Khetarpal, SA; Crosby, JR; Fornage, M; Isaacs, A; Jakobsdottir, J; Feitosa, MF; Davies, G; Huffman, JE; Manichaikul, A; Davis, B; Lohman, K; Joon, AY; Smith, AV; Grove, ML; Zanoni, P; Redon, V; Demissie, S; Lawson, K; Peters, U; Carlson, C; Jackson, RD; Ryckman, KK; Mackey, RH; Robinson, JG; Siscovick, DS; Schreiner, PJ; Mychaleckyj, JC; Pankow, JS; Hofman, A; Uitterlinden, AG; Harris, TB; Taylor, KD; Stafford, JM et al.
MLA Citation
Peloso, GM, Auer, PL, Bis, JC, Voorman, A, Morrison, AC, Stitziel, NO, Brody, JA, Khetarpal, SA, Crosby, JR, Fornage, M, Isaacs, A, Jakobsdottir, J, Feitosa, MF, Davies, G, Huffman, JE, Manichaikul, A, Davis, B, Lohman, K, Joon, AY, Smith, AV, Grove, ML, Zanoni, P, Redon, V, Demissie, S, Lawson, K, Peters, U, Carlson, C, Jackson, RD, Ryckman, KK, Mackey, RH, Robinson, JG, Siscovick, DS, Schreiner, PJ, Mychaleckyj, JC, Pankow, JS, Hofman, A, Uitterlinden, AG, Harris, TB, Taylor, KD, and Stafford, JM et al. "Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks." American journal of human genetics 94.2 (February 2014): 223-232.
PMID
24507774
Source
epmc
Published In
The American Journal of Human Genetics
Volume
94
Issue
2
Publish Date
2014
Start Page
223
End Page
232
DOI
10.1016/j.ajhg.2014.01.009

Are there negative responders to exercise training among heart failure patients?

PURPOSE: Aerobic exercise training has been used in patients with stable heart failure (HF) to reduce the risk of clinical events. However, due to patient heterogeneity, some patients may experience a decrease in functional capacity due to such training. The purpose of this study was to estimate the proportion of HF patients participating in a training program who had negative responses to such therapy and to compare them with a concurrent control group. METHODS: Baseline and 3-month peak V˙O2 measurements were obtained on 1870 HF subjects who were randomized to receive either an exercise training program or a control program of usual care without exercise training. The exercise program consisted of supervised walking or stationary cycling 3 d·wk(-1) for 12 wk as well as a 2-d·wk(-1) home exercise program after completing 18 supervised sessions. A negative response was defined as a baseline-to-3-month decrease in peak V˙O2 of at least 5 mL·kg(-1) min(-1), which was two times the SD of the control group's change in peak V˙O2. RESULTS: The mean ± SD change in peak V˙O2 in the exercise group and control group was 0.8 ± 2.5 mL·kg(-1)min(-1) and 0.2 ± 2.5 mL·kg(-1)min(-1), respectively (P < 0.001). The percentage of negative responders in the exercise and control groups was 0.9% and 2.3% (P = 0.02). CONCLUSIONS: The low negative response rate in the exercise group combined with the slightly higher rate in the control group and equal variability in the exercise and control groups suggests that few if any subjects had training-related negative peak V˙O2 responses. These findings support current exercise recommendations for HF patients.

Authors
Leifer, ES; Brawner, CA; Fleg, JL; Kraus, WE; Whellan, DJ; Piña, IL; Keteyian, SJ
MLA Citation
Leifer, ES, Brawner, CA, Fleg, JL, Kraus, WE, Whellan, DJ, Piña, IL, and Keteyian, SJ. "Are there negative responders to exercise training among heart failure patients?." Med Sci Sports Exerc 46.2 (February 2014): 219-224.
PMID
23860416
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
46
Issue
2
Publish Date
2014
Start Page
219
End Page
224
DOI
10.1249/MSS.0b013e3182a44164

Psychosocial benefits of cardiac rehabilitation among women compared with men

PURPOSE: Cardiac rehabilitation (CR) has been shown to reduce cardiac risk and improve the psychosocial functioning of participants. This study examines gender differences on several psychosocial indicators across the course of CR. METHODS: Patients (N = 380; 67.9% men and 32.1% women) referred from local inpatient and outpatient settings at a southeastern US academic medical facility were assessed on reported levels of depression, anxiety, panic, anger, and relationship satisfaction, using the Burns Brief Mood Survey, at the start and conclusion of a CR program. Medical variables were also assessed but are not the focus of this report. Statistical analyses included 1-way, Kruskal-Wallis, and repeated-measures analysis of variance procedures, as well as χ analyses. RESULTS: Women reported more psychosocial symptoms at pre-CR than men, and overall, both groups improved across CR. Women with significant depression, anxiety, and panic experienced clinically significant benefit across CR. Although the percentage of men reporting clinically significant levels of anger decreased significantly across CR, clinically significant levels of anger did not significantly change among women. In addition, women did not report benefits in relationship dissatisfaction. CONCLUSION: This study provides further evidence that CR offers psychosocial benefit for women, as has been reported in several small clinical samples. Some notable gender differences on anger and relationship satisfaction were observed. Clinical attention may be warranted to facilitate improvement for symptoms of anger and relationship concerns among selected women who participate in CR. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Authors
Hazelton, G; Williams, JW; Wakefield, J; Perlman, A; Kraus, WE; Wolever, RQ
MLA Citation
Hazelton, G, Williams, JW, Wakefield, J, Perlman, A, Kraus, WE, and Wolever, RQ. "Psychosocial benefits of cardiac rehabilitation among women compared with men." Journal of Cardiopulmonary Rehabilitation and Prevention 34.1 (January 1, 2014): 21-28.
Source
scopus
Published In
Journal of Cardiopulmonary Rehabilitation and Prevention
Volume
34
Issue
1
Publish Date
2014
Start Page
21
End Page
28
DOI
10.1097/HCR.0000000000000034

Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): A cohort analysis

Background The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain. We investigated whether baseline and change in objectively-assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance. Methods We assessed prospective data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January, 2002, and January, 2004. Participants also either had existing cardiovascular disease (if age ≥50 years) or at least one additional cardiovascular risk factor (if age =55 years). Participants were followed-up for cardiovascular events (defi ned as cardiovascular mortality, non-fatal stroke, or myocardial infarction) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months. Adjusted Cox proportional hazard models quantifi ed the association of baseline and change in ambulatory activity (from baseline to 12 months) with the risk of a subsequent cardiovascular event, after adjustment for each other and potential confounding variables. This study is registered with ClinicalTrials.gov NCT00097786. Findings During 45 211 person-years follow-up, 531 cardiovascular events occurred. Baseline ambulatory activity (hazard ratio [HR] per 2000 steps per day 0.90, 95% CI 0.84-0.96) and change in ambulatory activity (0.92, 0.86-0.99) were inversely associated with the risk of a cardiovascular event. Results for change in ambulatory activity were unaff ected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months. Interpretation In individuals at high cardiovascular risk with impaired glucose tolerance, both baseline levels of daily ambulatory activity and change in ambulatory activity display a graded inverse association with the subsequent risk of a cardiovascular event. Funding Novartis Pharmaceuticals.

Authors
Yates, T; Haffner, SM; Schulte, PJ; Thomas, L; Huffman, KM; Bales, CW; Califf, RM; Holman, RR; McMurray, JJV; Bethel, MA; Tuomilehto, J; Davies, MJ; Kraus, WE
MLA Citation
Yates, T, Haffner, SM, Schulte, PJ, Thomas, L, Huffman, KM, Bales, CW, Califf, RM, Holman, RR, McMurray, JJV, Bethel, MA, Tuomilehto, J, Davies, MJ, and Kraus, WE. "Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): A cohort analysis." The Lancet 383.9922 (January 1, 2014): 1059-1066.
Source
scopus
Published In
The Lancet
Volume
383
Issue
9922
Publish Date
2014
Start Page
1059
End Page
1066
DOI
10.1016/S0140-6736(13)62061-9

Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: Results from NAVIGATOR

Objective The cardiometabolic risk cluster metabolic syndrome (MS) includes ≥ 3 of elevated fasting glucose, hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-c), and increased waist circumference. Each can be affected by physical activity and diet. Our objective was to determine whether determine whether baseline physical activity and/or diet behavior impact MS in the course of a large pharmaceutical trial. Materials/Methods This was an observational study from NAVIGATOR, a double-blind, randomized (nateglinide, valsartan, both, or placebo), controlled trial between 2002 and 2004. We studied data from persons (n = 9306) with impaired glucose tolerance and cardiovascular disease (CVD) or CVD risk factors; 7118 with pedometer data were included in this analysis. Physical activity was assessed with 7-day pedometer records; diet behavior was self-reported on a 6-item survey. An MS score (MSSc) was calculated using the sum of each MS component, centered around the Adult Treatment Panel III threshold, and standardized according to sample standard deviation. Excepting HDL-c, assessed at baseline and year 3, MS components were assessed yearly. Follow-up averaged 6 years. Results For every 2000-step increase in average daily steps, there was an associated reduction in average MSSc of 0.29 (95% CI -0.33 to -0.25). For each diet behavior endorsed, there was an associated reduction in average MSSc of 0.05 (95% CI -0.08 to -0.01). Accounting for the effects of pedometer steps and diet behavior together had minimal impact on parameter estimates with no significant interaction. Relations were independent of age, sex, race, region, smoking, family history of diabetes, and use of nateglinide, valsartan, aspirin, antihypertensive, and lipid-lowering agent. Conclusions Baseline physical activity and diet behavior were associated independently with reductions in MSSc such that increased attention to these lifestyle elements provides cardiometabolic benefits. Thus, given the potential to impact outcomes, assessment of physical activity and diet should be performed in pharmacologic trials targeting cardiometabolic risk.

Authors
Huffman, KM; Sun, JL; Thomas, L; Bales, CW; Califf, RM; Yates, T; Davies, MJ; Holman, RR; Mcmurray, JJV; Bethel, MA; Tuomilehto, J; Haffner, SM; Kraus, WE
MLA Citation
Huffman, KM, Sun, JL, Thomas, L, Bales, CW, Califf, RM, Yates, T, Davies, MJ, Holman, RR, Mcmurray, JJV, Bethel, MA, Tuomilehto, J, Haffner, SM, and Kraus, WE. "Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: Results from NAVIGATOR." Metabolism: Clinical and Experimental 63.4 (January 1, 2014): 554-561.
Source
scopus
Published In
Metabolism
Volume
63
Issue
4
Publish Date
2014
Start Page
554
End Page
561
DOI
10.1016/j.metabol.2014.01.002

Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness

© 2014, Springer-Verlag Berlin Heidelberg.Methods: Subjects at risk of metabolic disease were randomised to 6 months of inactivity or one of five aerobic and/or resistance training programmes (n = 112). Pre/post-intervention assessments included cardiorespiratory fitness (V⋅ O2peak), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism.Results: Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of even-chain acylcarnitines (median 37–488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in V⋅ O2peak, TGs and SI (R = 0.20–0.31, p < 0.05). Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R = 0.39 and 0.24, p < 0.05) emerged as the strongest correlates of SI.Conclusions/interpretation: The metabolic signatures of exercise-trained skeletal muscle reflected reprogramming of mitochondrial function and intermediary metabolism and correlated with changes in cardiometabolic fitness. Succinate metabolism and the succinate dehydrogenase complex emerged as a potential regulatory node that intersects with whole-body insulin sensitivity. This study identifies new avenues for mechanistic research aimed at understanding the health benefits of physical activity.Trial registration ClinicalTrials.gov NCT00200993 and NCT00275145Funding This work was supported by the National Heart, Lung, and Blood Institute (National Institutes of Health), National Institute on Aging (National Institutes of Health) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health).Aims/hypothesis: Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms.

Authors
Huffman, KM; Koves, TR; Hubal, MJ; Abouassi, H; Beri, N; Bateman, LA; Stevens, RD; Ilkayeva, OR; Hoffman, EP; Muoio, DM; Kraus, WE
MLA Citation
Huffman, KM, Koves, TR, Hubal, MJ, Abouassi, H, Beri, N, Bateman, LA, Stevens, RD, Ilkayeva, OR, Hoffman, EP, Muoio, DM, and Kraus, WE. "Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness." Diabetologia 57.11 (January 1, 2014): 2282-2295.
Source
scopus
Published In
Diabetologia
Volume
57
Issue
11
Publish Date
2014
Start Page
2282
End Page
2295
DOI
10.1007/s00125-014-3343-4

Change in levels of physical activity after diagnosis of type 2 diabetes: An observational analysis from the NAVIGATOR study

© 2014 John Wiley & Sons Ltd.Increased physical activity is known to be beneficial in people with type 2 diabetes mellitus (T2DM), but it is not known whether individuals change their activity levels after T2DM diagnosis. The present Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, conducted in participants with impaired glucose tolerance at high cardiovascular risk, assessed ambulatory activity annually using research-grade pedometers. Oral glucose tolerance tests were performed annually and repeated to confirm T2DM diagnosis. This observational analysis used general linear models to compare step counts before and after T2DM diagnosis in the 2816 participants with the requisite data. Participants were relatively inactive at baseline, taking a median (interquartile range) of 5488 (3258-8361) steps/day, which decreased after T2DM diagnosis by a mean (s.e.) of 258 (64) steps/day (p < 0.0001); however, after adjusting for background trend for activity, step count after T2DM diagnosis was unchanged [mean (s.e.) of 103 (87) fewer steps/day; p = 0.23]. Awareness of T2DM diagnosis had no impact on the trajectory of activity established before the diagnosis.

Authors
Preiss, D; Haffner, SM; Thomas, LE; Sun, JL; Sattar, N; Yates, T; J Davies, M; Mcmurray, JJ; Holman, RR; Califf, RM; Kraus, WE
MLA Citation
Preiss, D, Haffner, SM, Thomas, LE, Sun, JL, Sattar, N, Yates, T, J Davies, M, Mcmurray, JJ, Holman, RR, Califf, RM, and Kraus, WE. "Change in levels of physical activity after diagnosis of type 2 diabetes: An observational analysis from the NAVIGATOR study." Diabetes, Obesity and Metabolism 16.12 (January 1, 2014): 1265-1268. (Letter)
Source
scopus
Published In
Diabetes Obesity & Metabolism
Volume
16
Issue
12
Publish Date
2014
Start Page
1265
End Page
1268
DOI
10.1111/dom.12320

Biological and Analytical Stability of a Peripheral Blood Gene Expression Score for Obstructive Coronary Artery Disease in the PREDICT and COMPASS Studies

© The Authors.A gene expression score (GES) for obstructive coronary artery disease (CAD) has been validated in two multicenter studies. Receiver-operating characteristics (ROC) analysis of the GES on an expanded Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD defined by quantitative coronary angiography (QCA) or clinical reads yielded similar performance (area under the curve (AUC) = 0.70, N = 1,502) to the original validation cohort (AUC = 0.70, N = 526). Analysis of 138 non-Caucasian and 1,364 Caucasian patients showed very similar performance (AUCs = 0.72 vs. 0.70). To assess analytic stability, stored samples of the original validation cohort (N = 526) was re-tested after 5 years, and the mean score changed from 20.3 to 19.8 after 5 years (N = 501, 95%). To assess patient scores over time, GES was determined on samples from 173 Coronary Obstruction Detection by Molecular Personalized Gene Expression (COMPASS) study (NCT no. 01117506) patients at approximately 1 year post-enrollment. Mean scores increased slightly from 15.9 to 17.3, corresponding to a 2.5% increase in obstructive CAD likelihood. Changes in cardiovascular medications did not show a significant change in GES.

Authors
Daniels, SE; Beineke, P; Rhees, B; McPherson, JA; Kraus, WE; Thomas, GS; Rosenberg, S
MLA Citation
Daniels, SE, Beineke, P, Rhees, B, McPherson, JA, Kraus, WE, Thomas, GS, and Rosenberg, S. "Biological and Analytical Stability of a Peripheral Blood Gene Expression Score for Obstructive Coronary Artery Disease in the PREDICT and COMPASS Studies." Journal of Cardiovascular Translational Research 7.7 (January 1, 2014): 615-622.
Source
scopus
Published In
Journal of Cardiovascular Translational Research
Volume
7
Issue
7
Publish Date
2014
Start Page
615
End Page
622
DOI
10.1007/s12265-014-9583-3

Energy requirements in nonobese men and women: results from CALERIE.

BACKGROUND: The energy intake necessary to maintain weight and body composition is called the energy requirement for weight maintenance and can be determined by using the doubly labeled water (DLW) method. OBJECTIVE: The objective was to determine the energy requirements of nonobese men and women in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy 2 study. DESIGN: Energy requirements were determined for 217 healthy, weight-stable men and women [aged >21 to <50 y; 70% female, 77% white; body mass index (BMI; in kg/m(2)) 22 to <28; 52% overweight] over 28 d with 2 consecutive 14-d DLW assessments in addition to serial measures of body weight and fat-free mass and fat mass by dual-energy X-ray absorptiometry. Energy intake and physical activity were also estimated by self-report over ≥6 consecutive d in each DLW period. RESULTS: Total daily energy expenditure (TDEE) was consistent between the 2 DLW studies (TDEE1: 2422 ± 404 kcal/d; TDEE2: 2465 ± 408 kcal/d; intraclass correlation coefficient = 0.90) with a mean TDEE of 2443 ± 397 kcal/d that was, on average, 20% (580 kcal/d) higher in men than in women (P < 0.0001). The regression equation relating mean TDEE to demographics and weight was as follows: TDEE (kcal/d) = 1279 + 18.3 (weight, kg) + 2.3 (age, y) - 338 (sex: 1 = female, 0 = male); R(2) = 0.57. When body composition was included, TDEE (kcal/d) = 454 + 38.7 (fat-free mass, kg) - 5.4 (fat mass, kg) + 4.7 (age in y) + 103 (sex: 1 = female, 0 = male); R(2) = 0.65. Individuals significantly underreported energy intake (350 kcal/d; 15%), and underreporting by overweight individuals (~400 kcal/d; 16%) was greater (P < 0.001) than that of normal-weight individuals (~270 kcal/d; 12%). Estimates of TDEE from a 7-d physical activity recall and measured resting metabolic rate also suggested that individuals significantly underreported physical activity (~400 kcal/d; 17%; P < 0.0001). CONCLUSION: These new equations derived over 1 mo during weight stability can be used to estimate the free-living caloric requirements of nonobese adults. This trial was registered at clinicaltrials.gov as NCT00427193.

Authors
Redman, LM; Kraus, WE; Bhapkar, M; Das, SK; Racette, SB; Martin, CK; Fontana, L; Wong, WW; Roberts, SB; Ravussin, E; CALERIE Study Group,
MLA Citation
Redman, LM, Kraus, WE, Bhapkar, M, Das, SK, Racette, SB, Martin, CK, Fontana, L, Wong, WW, Roberts, SB, Ravussin, E, and CALERIE Study Group, . "Energy requirements in nonobese men and women: results from CALERIE." Am J Clin Nutr 99.1 (January 2014): 71-78.
PMID
24257721
Source
pubmed
Published In
American Journal of Clinical Nutrition
Volume
99
Issue
1
Publish Date
2014
Start Page
71
End Page
78
DOI
10.3945/ajcn.113.065631

Relationship between galectin-3 levels and mineralocorticoid receptor antagonist use in heart failure: analysis from HF-ACTION.

BACKGROUND: Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION. METHODS AND RESULTS: HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II-IV, left ventricular ejection fraction ≤ 0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P = .76 for ACM+ACH; P = .26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.85-1.23, P = .8; and HR = 1.15, 95% CI [0.82-1.61], P = .4; respectively). IPW analysis was consistent with the results of the adjusted analysis. CONCLUSION: Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.

Authors
Fiuzat, M; Schulte, PJ; Felker, M; Ahmad, T; Neely, M; Adams, KF; Donahue, MP; Kraus, WE; Piña, IL; Whellan, DJ; O'Connor, CM
MLA Citation
Fiuzat, M, Schulte, PJ, Felker, M, Ahmad, T, Neely, M, Adams, KF, Donahue, MP, Kraus, WE, Piña, IL, Whellan, DJ, and O'Connor, CM. "Relationship between galectin-3 levels and mineralocorticoid receptor antagonist use in heart failure: analysis from HF-ACTION." J Card Fail 20.1 (January 2014): 38-44.
PMID
24304938
Source
pubmed
Published In
Journal of Cardiac Failure
Volume
20
Issue
1
Publish Date
2014
Start Page
38
End Page
44
DOI
10.1016/j.cardfail.2013.11.011

Psychosocial benefits of cardiac rehabilitation among women compared with men.

PURPOSE: Cardiac rehabilitation (CR) has been shown to reduce cardiac risk and improve the psychosocial functioning of participants. This study examines gender differences on several psychosocial indicators across the course of CR. METHODS: Patients (N = 380; 67.9% men and 32.1% women) referred from local inpatient and outpatient settings at a southeastern US academic medical facility were assessed on reported levels of depression, anxiety, panic, anger, and relationship satisfaction, using the Burns Brief Mood Survey, at the start and conclusion of a CR program. Medical variables were also assessed but are not the focus of this report. Statistical analyses included 1-way, Kruskal-Wallis, and repeated-measures analysis of variance procedures, as well as χ analyses. RESULTS: Women reported more psychosocial symptoms at pre-CR than men, and overall, both groups improved across CR. Women with significant depression, anxiety, and panic experienced clinically significant benefit across CR. Although the percentage of men reporting clinically significant levels of anger decreased significantly across CR, clinically significant levels of anger did not significantly change among women. In addition, women did not report benefits in relationship dissatisfaction. CONCLUSION: This study provides further evidence that CR offers psychosocial benefit for women, as has been reported in several small clinical samples. Some notable gender differences on anger and relationship satisfaction were observed. Clinical attention may be warranted to facilitate improvement for symptoms of anger and relationship concerns among selected women who participate in CR.

Authors
Hazelton, G; Williams, JW; Wakefield, J; Perlman, A; Kraus, WE; Wolever, RQ
MLA Citation
Hazelton, G, Williams, JW, Wakefield, J, Perlman, A, Kraus, WE, and Wolever, RQ. "Psychosocial benefits of cardiac rehabilitation among women compared with men." J Cardiopulm Rehabil Prev 34.1 (January 2014): 21-28.
PMID
24326900
Source
pubmed
Published In
Journal of Cardiopulmonary Rehabilitation and Prevention
Volume
34
Issue
1
Publish Date
2014
Start Page
21
End Page
28
DOI
10.1097/HCR.0000000000000034

Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization.

OBJECTIVE: To validate independent associations between branched-chain amino acids (BCAA) and other metabolites with coronary artery disease (CAD). METHODS: We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequential patients undergoing cardiac catheterization. Significant CAD was defined as CADindex ≥ 32 (at least one vessel with ≥ 95% stenosis; N = 995) and no CAD as CADindex ≤ 23 and no previous cardiac events (N = 610). Individuals (N = 378) with CAD severity between these extremes were excluded. Principal components analysis (PCA) reduced large numbers of correlated metabolites into uncorrelated factors. Association between metabolite factors and significant CAD vs. no CAD was tested using logistic regression; and between metabolite factors and severity of CAD was tested using linear regression. RESULTS: Of twelve PCA-derived metabolite factors, two were associated with CAD in multivariable models: factor 10, composed of BCAA (adjusted odds ratio, OR, 1.20; 95% CI 1.05-1.35, p = 0.005) and factor 7, composed of short-chain acylcarnitines, which include byproducts of BCAA metabolism (adjusted OR 1.30; 95% CI 1.14-1.48, p = 0.001). After adjustment for glycated albumin (marker of insulin resistance [IR]) both factors 7 (p = 0.0001) and 10 (p = 0.004) remained associated with CAD. Severity of CAD as a continuous variable (including patients with non-obstructive disease) was associated with metabolite factors 2, 3, 6, 7, 8 and 9; only factors 7 and 10 were associated in multivariable models. CONCLUSIONS: We validated the independent association of metabolites involved in BCAA metabolism with CAD extremes. These metabolites may be reporting on novel mechanisms of CAD pathogenesis that are independent of IR and diabetes.

Authors
Bhattacharya, S; Granger, CB; Craig, D; Haynes, C; Bain, J; Stevens, RD; Hauser, ER; Newgard, CB; Kraus, WE; Newby, LK; Shah, SH
MLA Citation
Bhattacharya, S, Granger, CB, Craig, D, Haynes, C, Bain, J, Stevens, RD, Hauser, ER, Newgard, CB, Kraus, WE, Newby, LK, and Shah, SH. "Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization." Atherosclerosis 232.1 (January 2014): 191-196.
PMID
24401236
Source
pubmed
Published In
Atherosclerosis
Volume
232
Issue
1
Publish Date
2014
Start Page
191
End Page
196
DOI
10.1016/j.atherosclerosis.2013.10.036

Human and mouse skeletal muscle stem cells: convergent and divergent mechanisms of myogenesis.

Satellite cells are the chief contributor to skeletal muscle growth and regeneration. The study of mouse satellite cells has accelerated in recent years due to technical advancements in the isolation of these cells. The study of human satellite cells has lagged and thus little is known about how the biology of mouse and human satellite cells compare. We developed a flow cytometry-based method to prospectively isolate human skeletal muscle progenitors from the satellite cell pool using positive and negative selection markers. Results show that this pool is enriched in PAX7 expressing cells that possess robust myogenic potential including the ability to give rise to de novo muscle in vivo. We compared mouse and human satellite cells in culture and identify differences in the elaboration of the myogenic genetic program and in the sensitivity of the cells to cytokine stimulation. These results indicate that not all mechanisms regulating mouse satellite cell activation are conserved in human satellite cells and that such differences may impact the clinical translation of therapeutics validated in mouse models. Thus, the findings of this study are relevant to developing therapies to combat muscle disease.

Authors
Bareja, A; Holt, JA; Luo, G; Chang, C; Lin, J; Hinken, AC; Freudenberg, JM; Kraus, WE; Evans, WJ; Billin, AN
MLA Citation
Bareja, A, Holt, JA, Luo, G, Chang, C, Lin, J, Hinken, AC, Freudenberg, JM, Kraus, WE, Evans, WJ, and Billin, AN. "Human and mouse skeletal muscle stem cells: convergent and divergent mechanisms of myogenesis." PloS one 9.2 (January 2014): e90398-.
PMID
24587351
Source
epmc
Published In
PloS one
Volume
9
Issue
2
Publish Date
2014
Start Page
e90398
DOI
10.1371/journal.pone.0090398

Earbud-based sensor for the assessment of energy expenditure, HR, and VO2max.

The goal of this program was to determine the feasibility of a novel noninvasive, highly miniaturized optomechanical earbud sensor for accurately estimating total energy expenditure (TEE) and maximum oxygen consumption (VO2max). The optomechanical sensor module, small enough to fit inside commercial audio earbuds, was previously developed to provide a seamless way to measure blood flow information during daily life activities. The sensor module was configured to continuously measure physiological information via photoplethysmography and physical activity information via accelerometry. This information was digitized and sent to a microprocessor where digital signal-processing algorithms extract physiological metrics in real time. These metrics were streamed wirelessly from the earbud to a computer.In this study, 23 subjects of multiple physical habitus were divided into a training group of 14 subjects and a validation group of 9 subjects. Each subject underwent the same exercise measurement protocol consisting of treadmill-based cardiopulmonary exercise testing to reach VO2max. Benchmark sensors included a 12-lead ECG sensor for measuring HR, a calibrated treadmill for measuring distance and speed, and a gas-exchange analysis instrument for measuring TEE and VO2max. The earbud sensor was the device under test. Benchmark and device under test data collected from the 14-person training data set study were integrated into a preconceived statistical model for correlating benchmark data with earbud sensor data. Coefficients were optimized, and the optimized model was validated in the 9-person validation data set.It was observed that the earbud sensor estimated TEE and VO2max with mean ± SD percent estimation errors of -0.7 ± 7.4% and -3.2 ± 7.3%, respectively.The earbud sensor can accurately estimate TEE and VO2max during cardiopulmonary exercise testing.

Authors
Leboeuf, SF; Aumer, ME; Kraus, WE; Johnson, JL; Duscha, B
MLA Citation
Leboeuf, SF, Aumer, ME, Kraus, WE, Johnson, JL, and Duscha, B. "Earbud-based sensor for the assessment of energy expenditure, HR, and VO2max." Medicine and science in sports and exercise 46.5 (January 2014): 1046-1052.
PMID
24743110
Source
epmc
Published In
Medicine and Science in Sports and Exercise
Volume
46
Issue
5
Publish Date
2014
Start Page
1046
End Page
1052
DOI
10.1249/mss.0000000000000183

The relationship between the blood pressure responses to exercise following training and detraining periods.

Exercise training lowers blood pressure (BP), while BP increases and returns to pre-training values with detraining. Yet, there is considerable variability in these BP responses. We examined the relationship between the BP responses after 6 months of training followed by 2 weeks of detraining among the same people.Subjects (n = 75) (X+SD, 50.2 ± 10.6 yr) were sedentary, obese, and had prehypertension. They completed an aerobic (n = 34); resistance (n = 28); or aerobic + resistance or concurrent (n = 13) exercise training program. We calculated a metabolic syndrome z score (MetSz). Subjects were classified as BP responders (BP decreased) or non-responders (BP increased) to training and detraining. Linear and multivariable regression tested the BP response. Chi Square tested the frequency of responders and non-responders. The systolic BP (SBP, r =  -0.474) and diastolic (DBP, r =  -0.540) response to training negatively correlated with detraining (p<0.01), independent of modality (p>0.05). Exercise responders reduced SBP 11.5 ± 7.8 (n = 29) and DBP 9.8 ± 6.2 mmHg (n = 31); non-responders increased SBP 7.9.± 10.9 (n = 46) and DBP 4.9 ± 7.1 mmHg (n = 44) (p<0.001). We found 65.5% of SBP training responders were SBP detraining non-responders; while 60.9% of SBP training non-responders were SBP detraining responders (p = 0.034). Similarly, 80.6% of DBP training responders were DBP detraining non-responders; while 59.1% of DBP training non-responders were DBP detraining responders (p<0.001). The SBP detraining response (r =  -0.521), resting SBP (r =  -0.444), and MetSz (r = 0.288) explained 44.8% of the SBP training response (p<0.001). The DBP detraining response (r =  -0.553), resting DBP (r =  -0.450), and MetSz (r = 0.463) explained 60.1% of the DBP training response (p<0.001).As expected most subjects that decreased BP after exercise training, increased BP after detraining. An unanticipated finding was most subjects that increased BP after exercise training, decreased BP after detraining. Reasons why the negative effects of exercise training on BP maybe reversed with detraining among some people should be explored further.ClinicalTrials.gov 1R01HL57354; 2003-2008; NCT00275145.

Authors
Moker, EA; Bateman, LA; Kraus, WE; Pescatello, LS
MLA Citation
Moker, EA, Bateman, LA, Kraus, WE, and Pescatello, LS. "The relationship between the blood pressure responses to exercise following training and detraining periods." PloS one 9.9 (January 2014): e105755-.
PMID
25208075
Source
epmc
Published In
PloS one
Volume
9
Issue
9
Publish Date
2014
Start Page
e105755
DOI
10.1371/journal.pone.0105755

A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.

Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.

Authors
Brummett, BH; Babyak, MA; Williams, RB; Harris, KM; Jiang, R; Kraus, WE; Singh, A; Costa, PT; Georgiades, A; Siegler, IC
MLA Citation
Brummett, BH, Babyak, MA, Williams, RB, Harris, KM, Jiang, R, Kraus, WE, Singh, A, Costa, PT, Georgiades, A, and Siegler, IC. "A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress." PloS one 9.12 (January 2014): e114451-.
PMID
25514629
Source
epmc
Published In
PloS one
Volume
9
Issue
12
Publish Date
2014
Start Page
e114451
DOI
10.1371/journal.pone.0114451

Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training

Authors
Allen, JD; Stabler, T; Kenjale, AA; Ham, KL; Robbins, JL; Duscha, BD; Kraus, WE; Annex, BH
MLA Citation
Allen, JD, Stabler, T, Kenjale, AA, Ham, KL, Robbins, JL, Duscha, BD, Kraus, WE, and Annex, BH. "Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training." Journal of Diabetes and its Complications 28.2 (2014): 219-225.
Source
scopus
Published In
Journal of Diabetes and its Complications
Volume
28
Issue
2
Publish Date
2014
Start Page
219
End Page
225

Design considerations for an integrated microphysiological muscle tissue for drug and tissue toxicity testing

Microphysiological systems provide a tool to simulate normal and pathological function of organs for prolonged periods. These systems must incorporate the key functions of the individual organs and enable interactions among the corresponding microphysiological units. The relative size of different microphysiological organs and their flow rates are scaled in proportion to in vivo values. We have developed a microphysiological three-dimensional engineered human skeletal muscle system connected to a circulatory system that consists of a tissue-engineered blood vessel as part of a high-pressure arterial system. The engineered human skeletal muscle tissue reproduces key mechanical behaviors of skeletal muscle in vivo. Pulsatile flow is produced using a novel computer-controlled magnetically activated ferrogel. The system is versatile and the muscle unit can be integrated with other organ systems. Periodic monitoring of biomechanical function provides a non-invasive assessment of the health of the tissue and a way to measure the response to drugs and toxins. © 2013 BioMed Central Ltd.

Authors
Truskey, GA; Achneck, HE; Bursac, N; Chan, HF; Cheng, CS; Fernandez, C; Hong, S; Jung, Y; Koves, T; Kraus, WE; Leong, K; Madden, L; Reichert, WM; Zhao, X
MLA Citation
Truskey, GA, Achneck, HE, Bursac, N, Chan, HF, Cheng, CS, Fernandez, C, Hong, S, Jung, Y, Koves, T, Kraus, WE, Leong, K, Madden, L, Reichert, WM, and Zhao, X. "Design considerations for an integrated microphysiological muscle tissue for drug and tissue toxicity testing." Stem Cell Research and Therapy 4.SUPPL.1 (December 20, 2013). (Review)
PMID
24565225
Source
scopus
Published In
Stem Cell Research and Therapy
Volume
4
Issue
SUPPL.1
Publish Date
2013
DOI
10.1186/scrt371

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmedor stochastic nature of hypomethylation, identifyingthesechanges is important in understanding vascular disease,asmaintenance ofacells' epigenetic profile is essential for maintaining cellularphenotype. Global hypomethylation of proliferating aorticSMCsandconcomitant decrease ofDNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by 'genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2'-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P 5 0.017, OR 5 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex disease. © The Author 2013.

Authors
Connelly, JJ; Cherepanova, OA; Doss, JF; Karaoli, T; Lillard, TS; Markunas, CA; Nelson, S; Wang, T; Ellis, PD; Langford, CF; Haynes, C; Seo, DM; Goldschmidt-Clermont, PJ; Shah, SH; Kraus, WE; Hauser, ER; Gregory, SG
MLA Citation
Connelly, JJ, Cherepanova, OA, Doss, JF, Karaoli, T, Lillard, TS, Markunas, CA, Nelson, S, Wang, T, Ellis, PD, Langford, CF, Haynes, C, Seo, DM, Goldschmidt-Clermont, PJ, Shah, SH, Kraus, WE, Hauser, ER, and Gregory, SG. "Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis." Human Molecular Genetics 22.25 (December 1, 2013): 5107-5120.
PMID
23912340
Source
scopus
Published In
Human Molecular Genetics
Volume
22
Issue
25
Publish Date
2013
Start Page
5107
End Page
5120
DOI
10.1093/hmg/ddt365

Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort

We performed a gene-smoking interaction analysis using families from an early-onset coronary artery disease cohort (GENECARD). This analysis was focused on validating and expanding results from previous studies implicating single nucleotide polymorphisms (SNPs) on chromosome 3 in smoking-mediated coronary artery disease. We analyzed 430 SNPs on chromosome 3 and identified 16 SNPs that showed a gene-smoking interaction at P < 0.05 using association in the presence of linkage-ordered subset analysis, a method that uses permutations of the data to empirically estimate the strength of the association signal. Seven of the 16 SNPs were in the Rho-GTPase pathway indicating a 1.87-fold enrichment for this pathway. A meta-analysis of gene-smoking interactions in three independent studies revealed that rs9289231 in KALRN had a Fisher's combined P value of 0.0017 for the interaction with smoking. In a gene-based meta-analysis KALRN had a P value of 0.026. Finally, a pathway-based analysis of the association results using WebGestalt revealed several enriched pathways including the regulation of the actin cytoskeleton pathway as defined by the Kyoto Encyclopedia of Genes and Genomes. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Ward-Caviness, C; Haynes, C; Blach, C; Dowdy, E; Gregory, SG; Shah, SH; Horne, BD; Kraus, WE; Hauser, ER
MLA Citation
Ward-Caviness, C, Haynes, C, Blach, C, Dowdy, E, Gregory, SG, Shah, SH, Horne, BD, Kraus, WE, and Hauser, ER. "Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort." Human Genetics 132.12 (December 1, 2013): 1371-1382.
Source
scopus
Published In
Human Genetics
Volume
132
Issue
12
Publish Date
2013
Start Page
1371
End Page
1382
DOI
10.1007/s00439-013-1339-7

Angiogenesis in peripheral artery disease: An emerging therapy targeting skeletal muscle

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities causing claudication, exercise intolerance and a decreased quality of life. Despite the fact that stenosis of conduit vessels are largely responsible for PAD diagnosis, and re-vascularization of these arteries are routinely performed as a treatment strategy, hemodynamics of conduit vessels do not entirely explain the functional limitation observed in PAD patients. Due to the inherent purpose the microvasculature plays in blood delivery and oxygen exchange to skeletal muscle, angiogenesis of the microvasculature may play a prominent role in PAD and has become the focus of both basic science and a therapeutic target for PAD clinical trials. This review will discuss what is currently known about skeletal muscle capillary density in PAD patients compared to normal subjects, how capillary density relates to exercise intolerance and how exercise training may be the best therapeutic intervention for initiating angiogenesis to improve exercise tolerance. Last, we will discuss the mechanisms of angiogenesis in skeletal muscle and the use of growth factors in therapeutic clinical trials. © 2013 by Nova Science Publishers, Inc. All rights reserved.

Authors
Duscha, BD; Robbins, JL; Kontos, CD; Kraus, WE; Annex, BH
MLA Citation
Duscha, BD, Robbins, JL, Kontos, CD, Kraus, WE, and Annex, BH. "Angiogenesis in peripheral artery disease: An emerging therapy targeting skeletal muscle." (December 1, 2013): 99-134. (Chapter)
Source
scopus
Publish Date
2013
Start Page
99
End Page
134

Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort.

We performed a gene-smoking interaction analysis using families from an early-onset coronary artery disease cohort (GENECARD). This analysis was focused on validating and expanding results from previous studies implicating single nucleotide polymorphisms (SNPs) on chromosome 3 in smoking-mediated coronary artery disease. We analyzed 430 SNPs on chromosome 3 and identified 16 SNPs that showed a gene-smoking interaction at P < 0.05 using association in the presence of linkage--ordered subset analysis, a method that uses permutations of the data to empirically estimate the strength of the association signal. Seven of the 16 SNPs were in the Rho-GTPase pathway indicating a 1.87-fold enrichment for this pathway. A meta-analysis of gene-smoking interactions in three independent studies revealed that rs9289231 in KALRN had a Fisher's combined P value of 0.0017 for the interaction with smoking. In a gene-based meta-analysis KALRN had a P value of 0.026. Finally, a pathway-based analysis of the association results using WebGestalt revealed several enriched pathways including the regulation of the actin cytoskeleton pathway as defined by the Kyoto Encyclopedia of Genes and Genomes.

Authors
Ward-Caviness, C; Haynes, C; Blach, C; Dowdy, E; Gregory, SG; Shah, SH; Horne, BD; Kraus, WE; Hauser, ER
MLA Citation
Ward-Caviness, C, Haynes, C, Blach, C, Dowdy, E, Gregory, SG, Shah, SH, Horne, BD, Kraus, WE, and Hauser, ER. "Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort." Hum Genet 132.12 (December 2013): 1371-1382.
PMID
23907653
Source
pubmed
Published In
Human Genetics
Volume
132
Issue
12
Publish Date
2013
Start Page
1371
End Page
1382
DOI
10.1007/s00439-013-1339-7

Peripheral Metabolite Profiles Predict Cardiomyopathy in a Cohort of Cardiac Catheterization Patients

Authors
Aras, MA; Craig, DM; Haynes, C; Bain, JR; Muehlbauer, MJ; Stevens, RD; Ilkayeva, O; Velazquez, EJ; Hernandez, AF; Newgard, C; Kraus, WE; Shah, SH
MLA Citation
Aras, MA, Craig, DM, Haynes, C, Bain, JR, Muehlbauer, MJ, Stevens, RD, Ilkayeva, O, Velazquez, EJ, Hernandez, AF, Newgard, C, Kraus, WE, and Shah, SH. "Peripheral Metabolite Profiles Predict Cardiomyopathy in a Cohort of Cardiac Catheterization Patients." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

Incremental Prognostic Utility by Cost and Complexity in Chronic Heart Failure

Authors
Ahmad, T; Fiuzat, M; Stevens, S; Schulte, P; Kraus, WE; Whellan, D; Kitzman, D; Zannad, F; Pina, I; Donahue, M; Adams, KF; Connor, CO; Felker, GM
MLA Citation
Ahmad, T, Fiuzat, M, Stevens, S, Schulte, P, Kraus, WE, Whellan, D, Kitzman, D, Zannad, F, Pina, I, Donahue, M, Adams, KF, Connor, CO, and Felker, GM. "Incremental Prognostic Utility by Cost and Complexity in Chronic Heart Failure." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

Effect of SLCO1B1*5 on Low-Density Lipoprotein Cholesterol Levels and Long-Term Clinical Events in Patients During Statin Therapy Following Cardiac Catheterization

Authors
Li, JH; Suchindran, S; Shah, SH; Kraus, WE; Ginsburg, GS; Voora, D
MLA Citation
Li, JH, Suchindran, S, Shah, SH, Kraus, WE, Ginsburg, GS, and Voora, D. "Effect of SLCO1B1*5 on Low-Density Lipoprotein Cholesterol Levels and Long-Term Clinical Events in Patients During Statin Therapy Following Cardiac Catheterization." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

Rare Variants Identified With Whole Exome Chip Genotyping Are Associated With Insulin Resistance and Glycemic Control

Authors
Shah, SH; Kwee, L; Stitziel, N; Hauser, ER; Haynes, C; Kathiresan, S; Gregory, SG; Kraus, WE
MLA Citation
Shah, SH, Kwee, L, Stitziel, N, Hauser, ER, Haynes, C, Kathiresan, S, Gregory, SG, and Kraus, WE. "Rare Variants Identified With Whole Exome Chip Genotyping Are Associated With Insulin Resistance and Glycemic Control." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

A Peripheral Blood Gene Expression Score for Obstructive Coronary Artery Disease is Significantly Associated With Major Adverse Cardiovascular Events and Revascularizations in the PREDICT Trial

Authors
McPherson, JA; Kraus, WE; Voros, S; Topol, EJ; Rhees, B; Daniels, SE; Kwon, DS; Wingrove, J; Littleford, L; Beineke, P; Rosenberg, S
MLA Citation
McPherson, JA, Kraus, WE, Voros, S, Topol, EJ, Rhees, B, Daniels, SE, Kwon, DS, Wingrove, J, Littleford, L, Beineke, P, and Rosenberg, S. "A Peripheral Blood Gene Expression Score for Obstructive Coronary Artery Disease is Significantly Associated With Major Adverse Cardiovascular Events and Revascularizations in the PREDICT Trial." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

High-density Lipoprotein Particle Concentration Has a Stronger Inverse Association With Cardiovascular Events Than High-density Lipoprotein Cholesterol in a Coronary Catheterization Population

Authors
McGarrah, RW; Craig, DM; Haynes, C; Dowdy, ZE; Shah, SH; Kraus, WE
MLA Citation
McGarrah, RW, Craig, DM, Haynes, C, Dowdy, ZE, Shah, SH, and Kraus, WE. "High-density Lipoprotein Particle Concentration Has a Stronger Inverse Association With Cardiovascular Events Than High-density Lipoprotein Cholesterol in a Coronary Catheterization Population." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

Metabolomic Profiling in a Human Model of Myocardial Infarction Identifies Novel Early Biomarkers of Cellular Damage

Authors
Shah, SH; Kraus, WE; Ilkaveva, O; Stevens, R; Haynes, C; Lewis, GD; Newgard, CB; Gerszten, RE
MLA Citation
Shah, SH, Kraus, WE, Ilkaveva, O, Stevens, R, Haynes, C, Lewis, GD, Newgard, CB, and Gerszten, RE. "Metabolomic Profiling in a Human Model of Myocardial Infarction Identifies Novel Early Biomarkers of Cellular Damage." November 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
128
Issue
22
Publish Date
2013

Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes.

BACKGROUND: ST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study-a multicenter, randomized study of exercise training in HF. METHODS AND RESULTS: HF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6-31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: ST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk. CLINICAL TRIAL INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Authors
Felker, GM; Fiuzat, M; Thompson, V; Shaw, LK; Neely, ML; Adams, KF; Whellan, DJ; Donahue, MP; Ahmad, T; Kitzman, DW; Piña, IL; Zannad, F; Kraus, WE; O'Connor, CM
MLA Citation
Felker, GM, Fiuzat, M, Thompson, V, Shaw, LK, Neely, ML, Adams, KF, Whellan, DJ, Donahue, MP, Ahmad, T, Kitzman, DW, Piña, IL, Zannad, F, Kraus, WE, and O'Connor, CM. "Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes." Circ Heart Fail 6.6 (November 2013): 1172-1179.
PMID
24103327
Source
pubmed
Published In
Circulation. Heart failure
Volume
6
Issue
6
Publish Date
2013
Start Page
1172
End Page
1179
DOI
10.1161/CIRCHEARTFAILURE.113.000207

Association between hemoglobin level and cardiopulmonary performance in heart failure: Insights from the HF-ACTION study

Authors
Cohen-Solal, A; Keteyian, SJ; Horton, JR; Ellis, SJ; Kraus, WE; Kilpatrick, RD
MLA Citation
Cohen-Solal, A, Keteyian, SJ, Horton, JR, Ellis, SJ, Kraus, WE, and Kilpatrick, RD. "Association between hemoglobin level and cardiopulmonary performance in heart failure: Insights from the HF-ACTION study." International Journal of Cardiology 168.4 (October 9, 2013): 4357-4359. (Letter)
Source
scopus
Published In
International Journal of Cardiology
Volume
168
Issue
4
Publish Date
2013
Start Page
4357
End Page
4359
DOI
10.1016/j.ijcard.2013.05.070

Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events.

The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin.Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biological pathways that may underlie these events.Aspirin was administered, followed by whole-blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1) (n = 50) and 2 validation cohorts of healthy volunteers (HV2) (n = 53) and outpatient cardiology patients (OPC) (n = 25). Platelet function was assessed using the platelet function score (PFS) in HV1 and HV2 and the VerifyNow Aspirin Test (Accumetrics, Inc., San Diego, California) in OPC. Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for associations with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death or MI in 2 patient cohorts (n = 587 total) from RNA samples collected at cardiac catheterization.A set of 60 coexpressed genes named the "aspirin response signature" (ARS) was associated with PFS in HV1 (r = -0.31, p = 0.03), HV2 (r = -0.34, Bonferroni p = 0.03), and OPC (p = 0.046). Corresponding proteins for the 17 ARS genes were identified in the platelet proteome, of which 6 were associated with PFS. The ARS was associated with death or MI in both patient cohorts (odds ratio: 1.2 [p = 0.01]; hazard ratio: 1.5 [p = 0.001]), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index = 31% to 37%, p ≤ 0.0002) was improved by including the ARS or 1 of its genes, ITGA2B.RNA profiles of platelet-specific genes are novel biomarkers for identifying patients who do not respond adequately to aspirin and who are at risk for death or MI.

Authors
Voora, D; Cyr, D; Lucas, J; Chi, J-T; Dungan, J; McCaffrey, TA; Katz, R; Newby, LK; Kraus, WE; Becker, RC; Ortel, TL; Ginsburg, GS
MLA Citation
Voora, D, Cyr, D, Lucas, J, Chi, J-T, Dungan, J, McCaffrey, TA, Katz, R, Newby, LK, Kraus, WE, Becker, RC, Ortel, TL, and Ginsburg, GS. "Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events." Journal of the American College of Cardiology 62.14 (October 2013): 1267-1276.
PMID
23831034
Source
epmc
Published In
JACC - Journal of the American College of Cardiology
Volume
62
Issue
14
Publish Date
2013
Start Page
1267
End Page
1276
DOI
10.1016/j.jacc.2013.05.073

Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial".

Advancing age is associated with an increase in physical impairment, functional limitations, disability, and loss of independence. Regular physical activity conveys health benefits, but the yield on physical function in the elderly, is less clear. Current exercise guidelines are focused predominantly on aerobic programs despite evidence that age-associated declines are mediated by peripheral tissue changes. The Fit for Life trial proposes a new paradigm of exercise training for the elderly that uses a low-mass high-repetition training regimen specifically focused on peripheral tissue beds or body regions (Regional Specific Training Stimulus - RSTS). RSTS is designed to deliver a localized stimulus to the peripheral vasculature, bone and muscle, without imposing a significant central cardiorespiratory strain. The purpose of this study is three-fold; 1) to derive effect sizes from the RSTS intervention by which to power a subsequent larger, confirmatory trial; 2) to assess fidelity of the RSTS intervention; and 3) to assess the interrelationship of the primary endpoints of physical impairment/fitness (VO(2peak), 1 repetition maximal contraction) and function (Senior Fitness Test scores) following two versions of a 4 + 8 week protocol. Men and women over 70 years, at risk for losing independence will be randomized to either 4 weeks of RSTS or "aerobic" exercise, followed by an identical 8 weeks of progressive whole-body training (aerobic plus resistance). The guiding hypothesis is that the magnitude of adaptation after 12 weeks will be greatest in those initially randomized to RSTS. Possible mediators of the intervention effect - physical impairment/fitness and function relationship, including vascular function, muscle mass, strength, and physiology will also be assessed.

Authors
Allen, JD; Robbins, JL; Vanbruggen, MD; Credeur, DP; Johannsen, NM; Earnest, CP; Pieper, CF; Johnson, JL; Church, TS; Ravussin, E; Kraus, WE; Welsch, MA
MLA Citation
Allen, JD, Robbins, JL, Vanbruggen, MD, Credeur, DP, Johannsen, NM, Earnest, CP, Pieper, CF, Johnson, JL, Church, TS, Ravussin, E, Kraus, WE, and Welsch, MA. "Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial"." Contemp Clin Trials 36.1 (September 2013): 266-275.
PMID
23900005
Source
pubmed
Published In
Contemporary Clinical Trials
Volume
36
Issue
1
Publish Date
2013
Start Page
266
End Page
275
DOI
10.1016/j.cct.2013.07.007

Effects of Exercise Amount and Intensity versus Lifestyle Intervention on Metabolic Syndrome in Adults With Prediabetes-STRRIDE PD

Authors
Bateman, LA; Slentz, CA; Willis, LH; Granville, E; Piner, LW; Bales, CA; Kraus, WE
MLA Citation
Bateman, LA, Slentz, CA, Willis, LH, Granville, E, Piner, LW, Bales, CA, and Kraus, WE. "Effects of Exercise Amount and Intensity versus Lifestyle Intervention on Metabolic Syndrome in Adults With Prediabetes-STRRIDE PD." DIABETES 62 (July 2013): A188-A188.
Source
wos-lite
Published In
Diabetes
Volume
62
Publish Date
2013
Start Page
A188
End Page
A188

Effects of Exercise Amount and Intensity versus a Lifestyle Intervention on Fasting Glucose in Adults With Pre-diabetes-STRRIDE-PD

Authors
Willis, LH; Slentz, CA; Bateman, LA; Granviille, E; Piner, LW; Bales, CW; Kraus, WE
MLA Citation
Willis, LH, Slentz, CA, Bateman, LA, Granviille, E, Piner, LW, Bales, CW, and Kraus, WE. "Effects of Exercise Amount and Intensity versus a Lifestyle Intervention on Fasting Glucose in Adults With Pre-diabetes-STRRIDE-PD." DIABETES 62 (July 2013): A186-A186.
Source
wos-lite
Published In
Diabetes
Volume
62
Publish Date
2013
Start Page
A186
End Page
A186

Comparison of Lipoprotein-Derived Insulin Resistance Score and Standard Measures of Insulin Sensitivity

Authors
Mikus, CR; Patel, MJ; Slentz, CA; Bateman, LA; Willis, LH; Kraus, WE
MLA Citation
Mikus, CR, Patel, MJ, Slentz, CA, Bateman, LA, Willis, LH, and Kraus, WE. "Comparison of Lipoprotein-Derived Insulin Resistance Score and Standard Measures of Insulin Sensitivity." DIABETES 62 (July 2013): A167-A167.
Source
wos-lite
Published In
Diabetes
Volume
62
Publish Date
2013
Start Page
A167
End Page
A167

Effects of Exercise Amount and Intensity versus Lifestyle Intervention on Glucose Tolerance in Adults With Prediabetes-STRRIDE PD

Authors
Slentz, CA; Bateman, LA; Willis, LH; Granville, E; Piner, LW; Elliot-Penry, L; Bales, CW; Kraus, WE
MLA Citation
Slentz, CA, Bateman, LA, Willis, LH, Granville, E, Piner, LW, Elliot-Penry, L, Bales, CW, and Kraus, WE. "Effects of Exercise Amount and Intensity versus Lifestyle Intervention on Glucose Tolerance in Adults With Prediabetes-STRRIDE PD." DIABETES 62 (July 2013): A184-A184.
Source
wos-lite
Published In
Diabetes
Volume
62
Publish Date
2013
Start Page
A184
End Page
A184

Trajectory classes of body mass index in a representative elderly community sample.

BACKGROUND: It is unclear whether distinct weight-related trajectory classes, differing in course, demographics, and health characteristics, exist in the elderly population. METHODS: Data came from the 10-year (1986-1996) Duke Established Populations for Epidemiologic Studies of the Elderly study of 3,861 black (54%) and white (46%) participants aged 65-105 years. Latent-class trajectories of body mass index (BMI: kg/m(2)) based on self-reported weight and height at baseline, 3, 6, and 10 years later were determined using generalized mixture models. Polytomous logistic regression was used to identify baseline demographic and health characteristics that distinguished the trajectories, and 10-year postbaseline data to confirm the findings. RESULTS: We identified three trajectories: normal weight (BMI ~24, 27.6% of the sample), overweight (BMI ~26, 65.1%), and obese (BMI ~31, 7.3%). Demographic characteristics distinguished the three trajectories: highest odds of blacks, women, and less education in the obese trajectory, lowest in the normal-weight trajectory. Obese and overweight differed adversely from normal-weight trajectories, but not significantly from each other on cognitive impairment, hypertension, and diabetes. Depressive symptomatology was more prevalent in the obese; they were also younger. There was no association with cancer or heart disease. CONCLUSION: Distinct trajectories and course of BMI were present in this older population. Weight loss increased with increase in BMI class. Although demographic characteristics distinguished all trajectory classes, adverse health characteristics distinguished the overweight and obese classes from the normal-weight class, but not from each other. Problems associated with education and health are present at study entry and should be addressed earlier in life.

Authors
Kuchibhatla, MN; Fillenbaum, GG; Kraus, WE; Cohen, HJ; Blazer, DG
MLA Citation
Kuchibhatla, MN, Fillenbaum, GG, Kraus, WE, Cohen, HJ, and Blazer, DG. "Trajectory classes of body mass index in a representative elderly community sample." J Gerontol A Biol Sci Med Sci 68.6 (June 2013): 699-704.
PMID
23089335
Source
pubmed
Published In
Journals of Gerontology: Series A
Volume
68
Issue
6
Publish Date
2013
Start Page
699
End Page
704
DOI
10.1093/gerona/gls215

Trajectory Classes of Body Mass Index in a Representative Elderly Community Sample

Authors
Kuchibhatla, MN; Fillenbaum, GG; Kraus, WE; Cohen, HJ; Blazer, DG
MLA Citation
Kuchibhatla, MN, Fillenbaum, GG, Kraus, WE, Cohen, HJ, and Blazer, DG. "Trajectory Classes of Body Mass Index in a Representative Elderly Community Sample." JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 68.6 (June 2013): 699-704.
Source
wos-lite
Published In
Journals of Gerontology: Series A
Volume
68
Issue
6
Publish Date
2013
Start Page
699
End Page
704
DOI
10.1093/gerona/gls215

Oxygen Uptake Efficiency Slope (oues): Maximal Vs. Submaximal Calculation Methods

Authors
Ehrman, JK; Kraus, WE; Piner, LW; Leifer, ES; Saval, MA; Keteyian, SJ; Brawner, CA
MLA Citation
Ehrman, JK, Kraus, WE, Piner, LW, Leifer, ES, Saval, MA, Keteyian, SJ, and Brawner, CA. "Oxygen Uptake Efficiency Slope (oues): Maximal Vs. Submaximal Calculation Methods." May 2013.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
45
Issue
5
Publish Date
2013
Start Page
573
End Page
574

Cancer-specific concerns and physical activity among recently diagnosed breast and prostate cancer survivors.

BACKGROUND: Cancer treatment -related side effects may have a negative impact on quality of life among cancer survivors and may limit participation in physical activity (PA). HYPOTHESIS: Cancer-specific concerns will be reduced throughout a 10-month diet and exercise intervention among recently diagnosed cancer survivors. Additionally, participants reporting greater levels of PA will also report fewer cancer-specific concerns. STUDY DESIGN: This study is an exploratory analysis of 452 recently diagnosed, early-stage breast and prostate cancer survivors who participated in the FRESH START diet and exercise trial. Data were collected at baseline and 1-year follow-up. RESULTS: At baseline, chief concerns among prostate cancer survivors included ability to have an erection (mean score [standard deviation] = 1.0 [1.3]) and urinary frequency (2.5 [1.4]), whereas among breast cancer survivors, eminent concerns were not feeling sexually attractive (2.0 [1.3]) and worry about cancer in other members of their family (2.1 [1.3]). At 1 year, there was a significant improvement in cancer-specific concerns on breast cancer-specific concerns (P < .01) but not on prostate cancer-specific concerns. At baseline, women who were self-conscious about their dress had higher levels of PA, whereas men reporting issues with incontinence reported lesser increases in PA in response to the intervention. CONCLUSION: Cancer-specific concerns diminish over time, especially among breast cancer survivors. Among prostate cancer survivors, incontinence is a significant barrier that hinders benefit from PA interventions. Thus, there is a need either for medical interventions to ameliorate incontinence or for behavioral interventions to address this issue among survivors.

Authors
Ottenbacher, A; Sloane, R; Snyder, DC; Kraus, W; Sprod, L; Demark-Wahnefried, W
MLA Citation
Ottenbacher, A, Sloane, R, Snyder, DC, Kraus, W, Sprod, L, and Demark-Wahnefried, W. "Cancer-specific concerns and physical activity among recently diagnosed breast and prostate cancer survivors." Integr Cancer Ther 12.3 (May 2013): 206-212.
PMID
22879576
Source
pubmed
Published In
Integrative Cancer Therapies
Volume
12
Issue
3
Publish Date
2013
Start Page
206
End Page
212
DOI
10.1177/1534735412449734

Weight change, calorie intake, and macronutrient profiles for 6 and 12 month diet and exercise interventions in participants with pre-diabetes: Does duration of treatment make a difference?

Authors
Granville, EO; Starr, KN; Ratliff, A; Connor, LA; Slentz, CA; Bateman, LA; Willis, LH; Piner, L; Kraus, WE; Bales, CW
MLA Citation
Granville, EO, Starr, KN, Ratliff, A, Connor, LA, Slentz, CA, Bateman, LA, Willis, LH, Piner, L, Kraus, WE, and Bales, CW. "Weight change, calorie intake, and macronutrient profiles for 6 and 12 month diet and exercise interventions in participants with pre-diabetes: Does duration of treatment make a difference?." April 2013.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
27
Publish Date
2013

Influence of long-term exercise training followed by a diet/exercise weight-loss intervention on body composition and metabolic variables in subjects with pre-diabetes

Authors
Starr, KN; Granville, EO; Ocampo, CI; Slentz, CA; Bateman, LA; Willis, LH; Rose, SB; Kraus, WE; Bales, CW
MLA Citation
Starr, KN, Granville, EO, Ocampo, CI, Slentz, CA, Bateman, LA, Willis, LH, Rose, SB, Kraus, WE, and Bales, CW. "Influence of long-term exercise training followed by a diet/exercise weight-loss intervention on body composition and metabolic variables in subjects with pre-diabetes." April 2013.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
27
Publish Date
2013

Association of Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality with Peak VO2 in a Heart Failure Population

Authors
Kraus, WE; Donahue, MP; Shah, SH; Whellan, DJ; Hellkamp, A; O'Connor, CM; Felker, GM
MLA Citation
Kraus, WE, Donahue, MP, Shah, SH, Whellan, DJ, Hellkamp, A, O'Connor, CM, and Felker, GM. "Association of Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality with Peak VO2 in a Heart Failure Population." March 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
127
Issue
12
Publish Date
2013

Association of Gene Expression Signatures with Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality in CATHGEN

Authors
Kraus, WE; Feng, S; Hauser, ER; Gregory, SG; Haynes, C; Dowdy, ZE; Craig, DM; Shah, SH
MLA Citation
Kraus, WE, Feng, S, Hauser, ER, Gregory, SG, Haynes, C, Dowdy, ZE, Craig, DM, and Shah, SH. "Association of Gene Expression Signatures with Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality in CATHGEN." March 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
127
Issue
12
Publish Date
2013

Mobile Source Air Pollution is Associated with the Plasma Concentration of Multiple Acylcarnitines in a Large Cardiovascular Cohort

Authors
Ward-Caviness, C; Neas, L; Haynes, C; Blachi, C; Cascio, W; Devlin, R; Diaz-Sanchez, D; Kraus, WE; Shah, SH; Miranda, ML; Hauser, ER
MLA Citation
Ward-Caviness, C, Neas, L, Haynes, C, Blachi, C, Cascio, W, Devlin, R, Diaz-Sanchez, D, Kraus, WE, Shah, SH, Miranda, ML, and Hauser, ER. "Mobile Source Air Pollution is Associated with the Plasma Concentration of Multiple Acylcarnitines in a Large Cardiovascular Cohort." March 26, 2013.
Source
wos-lite
Published In
Circulation
Volume
127
Issue
12
Publish Date
2013

Association between adrenergic receptor genotypes and beta-blocker dose in heart failure patients: analysis from the HF-ACTION DNA substudy.

AIMS: Beta-blockers reduce morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction. However, there is heterogeneity in the response to these drugs, perhaps due to genetic variations in the β1-adrenergic receptor (ADRβ1). We examined whether the Arg389Gly polymorphism in ADRβ1 interacts with the dose requirements of beta-blockers in patients with systolic HF. METHODS AND RESULTS: HF-ACTION was a randomized, multicentre trial of ambulatory HF patients with systolic dysfunction who were randomized to exercise training or usual care. A subset of patients provided DNA. The relationships among beta-blocker dose, ADRβ1-389 genotype, and outcomes were assessed using the Cox proportional hazards regression model. The interaction between beta-blocker dose and the ADRβ1-389 genotype was tested. DNA information was available for 957 patients. The alleles did not deviate from Hardy-Weinberg equilibrium. Patients with the ADRβ1-389 Arg/Arg genotype receiving low-dose beta-blockers had a two-fold increase in the risk of death compared with those receiving a high dose (hazard ratio 2.09; P = 0.015); this was not conferred in Gly carriers. There was also an interaction between improvements in Kansas City Cardiomyopathy Questionnaire score and beta-blocker dose by genotype, suggesting that higher doses of beta-blockade might be needed to achieve benefit in Arg/Arg genotype patients. CONCLUSION: There was a gene-dose interaction with the ADRβ1-389 Arg/Arg vs. Gly carrier genotype and beta-blocker dose, suggesting that patients with the Arg/Arg genotype might require a higher dose of beta-blockade to achieve a treatment response similar to that of Gly carriers.

Authors
Fiuzat, M; Neely, ML; Starr, AZ; Kraus, WE; Felker, GM; Donahue, M; Adams, K; Piña, IL; Whellan, D; O'Connor, CM
MLA Citation
Fiuzat, M, Neely, ML, Starr, AZ, Kraus, WE, Felker, GM, Donahue, M, Adams, K, Piña, IL, Whellan, D, and O'Connor, CM. "Association between adrenergic receptor genotypes and beta-blocker dose in heart failure patients: analysis from the HF-ACTION DNA substudy." Eur J Heart Fail 15.3 (March 2013): 258-266.
PMID
23115322
Source
pubmed
Published In
European Journal of Heart Failure
Volume
15
Issue
3
Publish Date
2013
Start Page
258
End Page
266
DOI
10.1093/eurjhf/hfs175

A Gender-Specific Blood-Based Gene Expression Score for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients: Results of the Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) Trial

Authors
Lansky, A; Elashoff, MR; Ng, V; McPherson, J; Lazar, D; Kraus, WE
MLA Citation
Lansky, A, Elashoff, MR, Ng, V, McPherson, J, Lazar, D, and Kraus, WE. "A Gender-Specific Blood-Based Gene Expression Score for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients: Results of the Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) Trial." JOURNAL OF WOMENS HEALTH 22.3 (March 2013): 8-8.
Source
wos-lite
Published In
Journal of Women's Health
Volume
22
Issue
3
Publish Date
2013
Start Page
8
End Page
8

Clinical characteristics, response to exercise training, and outcomes in patients with heart failure and chronic obstructive pulmonary disease: findings from Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION).

BACKGROUND: The aim of this study was to investigate the clinical characteristics, exercise training response, β-blocker selectivity, and outcomes in patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD). METHODS: We performed an analysis of HF-ACTION, which randomized 2,331 patients with HF having an ejection fraction of ≤35% to usual care with or without aerobic exercise training. We examined clinical characteristics and outcomes (mortality/hospitalization, mortality, cardiovascular [CV] mortality/CV hospitalization, and CV mortality/HF hospitalization) by physician-reported COPD status using adjusted Cox models and explored an interaction with exercise training. The interaction between β-blocker cardioselectivity and outcomes was investigated. RESULTS: Of patients with COPD status documented (n = 2311), 11% (n = 249) had COPD. Patients with COPD were older, had more comorbidities, and had lower use of β-blockers compared with those without COPD. At baseline, patients with COPD had lower peak oxygen consumption and higher V(E)/V(CO)(2) slope. During a median follow-up of 2.5 years, COPD was associated with increased mortality/hospitalization, mortality, and CV mortality/HF hospitalization. After multivariable adjustment, the risk of CV mortality/HF hospitalization remained increased (hazard ratio [HR] 1.46, 95% CI 1.14-1.87), whereas mortality/hospitalization (HR 1.15, 95% CI 0.96-1.37) and mortality (HR 1.33, 95% CI 0.99-1.76) were not significantly increased. There was no interaction between COPD and exercise training on outcomes or between COPD and β-blocker selectivity on mortality/hospitalization (all P > .1). CONCLUSIONS: Chronic obstructive pulmonary disease in patients with HF was associated with older age, more comorbidities, reduced exercise capacity, and increased CV mortality/HF hospitalization, but not a differential response to exercise training. β-Blocker selectivity was not associated with differences in outcome for patients with vs without COPD.

Authors
Mentz, RJ; Schulte, PJ; Fleg, JL; Fiuzat, M; Kraus, WE; Piña, IL; Keteyian, SJ; Kitzman, DW; Whellan, DJ; Ellis, SJ; O'Connor, CM
MLA Citation
Mentz, RJ, Schulte, PJ, Fleg, JL, Fiuzat, M, Kraus, WE, Piña, IL, Keteyian, SJ, Kitzman, DW, Whellan, DJ, Ellis, SJ, and O'Connor, CM. "Clinical characteristics, response to exercise training, and outcomes in patients with heart failure and chronic obstructive pulmonary disease: findings from Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION)." Am Heart J 165.2 (February 2013): 193-199.
PMID
23351822
Source
pubmed
Published In
American Heart Journal
Volume
165
Issue
2
Publish Date
2013
Start Page
193
End Page
199
DOI
10.1016/j.ahj.2012.10.029

Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III.

We investigated the feasibility of using recombinant human acid-α glucosidase (rhGAA, Alglucosidase alfa), an FDA approved therapy for Pompe disease, as a treatment approach for glycogen storage disease type III (GSD III). An in vitro disease model was established by isolating primary myoblasts from skeletal muscle biopsies of patients with GSD IIIa. We demonstrated that rhGAA significantly reduced glycogen levels in the two GSD IIIa patients' muscle cells (by 17% and 48%, respectively) suggesting that rhGAA could be a novel therapy for GSD III. This conclusion needs to be confirmed in other in vivo models.

Authors
Sun, B; Fredrickson, K; Austin, S; Tolun, AA; Thurberg, BL; Kraus, WE; Bali, D; Chen, Y-T; Kishnani, PS
MLA Citation
Sun, B, Fredrickson, K, Austin, S, Tolun, AA, Thurberg, BL, Kraus, WE, Bali, D, Chen, Y-T, and Kishnani, PS. "Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III." Mol Genet Metab 108.2 (February 2013): 145-147.
PMID
23318145
Source
pubmed
Published In
Molecular Genetics and Metabolism
Volume
108
Issue
2
Publish Date
2013
Start Page
145
End Page
147
DOI
10.1016/j.ymgme.2012.12.002

Clinical characteristics, response to exercise training, and outcomes in patients with heart failure and chronic obstructive pulmonary disease: Findings from Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION)

Authors
Mentz, RJ; Schulte, PJ; Fleg, JL; Fiuzat, M; Kraus, WE; Pina, IL; Keteyian, SJ; Kitzman, DW; Whellan, DJ; Ellis, SJ; O'Connor, CM
MLA Citation
Mentz, RJ, Schulte, PJ, Fleg, JL, Fiuzat, M, Kraus, WE, Pina, IL, Keteyian, SJ, Kitzman, DW, Whellan, DJ, Ellis, SJ, and O'Connor, CM. "Clinical characteristics, response to exercise training, and outcomes in patients with heart failure and chronic obstructive pulmonary disease: Findings from Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION)." AMERICAN HEART JOURNAL 165.2 (February 2013): 193-199.
Source
wos-lite
Published In
American Heart Journal
Volume
165
Issue
2
Publish Date
2013
Start Page
193
End Page
199
DOI
10.1016/j.ahj.2012.10.029

Can lifestyle modification improve neurocognition? Rationale and design of the ENLIGHTEN clinical trial.

BACKGROUND: Risk factors for cardiovascular disease (CVD) not only increase the risk for clinical CVD events, but also are associated with a cascade of neurophysiologic and neuroanatomic changes that increase the risk of cognitive impairment and dementia. Although epidemiological studies have shown that exercise and diet are associated with lower CVD risk and reduced incidence of dementia, no randomized controlled trial (RCT) has examined the independent effects of exercise and diet on neurocognitive function among individuals at risk for dementia. The ENLIGHTEN trial is a RCT of patients with CVD risk factors who also are characterized by subjective cognitive complaints and objective evidence of neurocognitive impairment without dementia (CIND) STUDY DESIGN: A 2 by 2 design will examine the independent and combined effects of diet and exercise on neurocognition. 160 participants diagnosed with CIND will be randomly assigned to 6 months of aerobic exercise, the DASH diet, or a combination of both exercise and diet; a (control) group will receive health education but otherwise will maintain their usual dietary and activity habits. Participants will complete comprehensive assessments of neurocognitive functioning along with biomarkers of CVD risk including measures of blood pressure, glucose, endothelial function, and arterial stiffness. CONCLUSION: The ENLIGHTEN trial will (a) evaluate the effectiveness of aerobic exercise and the DASH diet in improving neurocognitive functioning in CIND patients with CVD risk factors; (b) examine possible mechanisms by which exercise and diet improve neurocognition; and (c) consider potential moderators of treatment, including subclinical CVD.

Authors
Blumenthal, JA; Smith, PJ; Welsh-Bohmer, K; Babyak, MA; Browndyke, J; Lin, P-H; Doraiswamy, PM; Burke, J; Kraus, W; Hinderliter, A; Sherwood, A
MLA Citation
Blumenthal, JA, Smith, PJ, Welsh-Bohmer, K, Babyak, MA, Browndyke, J, Lin, P-H, Doraiswamy, PM, Burke, J, Kraus, W, Hinderliter, A, and Sherwood, A. "Can lifestyle modification improve neurocognition? Rationale and design of the ENLIGHTEN clinical trial." Contemp Clin Trials 34.1 (January 2013): 60-69.
PMID
23000080
Source
pubmed
Published In
Contemporary Clinical Trials
Volume
34
Issue
1
Publish Date
2013
Start Page
60
End Page
69
DOI
10.1016/j.cct.2012.09.004

Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training

Authors
Allen, JD; Stabler, T; Kenjale, AA; Ham, KL; Robbins, JL; Duscha, BD; Kraus, WE; Annex, BH
MLA Citation
Allen, JD, Stabler, T, Kenjale, AA, Ham, KL, Robbins, JL, Duscha, BD, Kraus, WE, and Annex, BH. "Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training." Journal of Diabetes and its Complications (2013).
PMID
24355663
Source
scopus
Published In
Journal of Diabetes and its Complications
Publish Date
2013

The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure

Authors
Ahmad, T; Fiuzat, M; Mark, DB; Neely, B; Neely, M; Kraus, WE; Kitzman, DW; Whellan, DJ; Donahue, M; Zannad, F; Piña, IL; Adams, K; O'Connor, CM; Felker, GM
MLA Citation
Ahmad, T, Fiuzat, M, Mark, DB, Neely, B, Neely, M, Kraus, WE, Kitzman, DW, Whellan, DJ, Donahue, M, Zannad, F, Piña, IL, Adams, K, O'Connor, CM, and Felker, GM. "The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure." American Heart Journal (2013).
PMID
24439980
Source
scopus
Published In
American Heart Journal
Publish Date
2013

Moderate-intensity aerobic training program improves insulin sensitivity and inflammatory markers in a pilot study of morbidly obese minority teens

We initiated a pilot study to investigate the effects of 8 wks of aerobic exercise training (ET) on insulin sensitivity and inflammatory markers in obese and insulin-resistant minority adolescents. Eleven morbidly obese (BMI 41.4 ± 1.8 kg/m2) minority adolescents were entered into a supervised ET intervention (∼180 min/wk at 40-55%VO2PeakR [(VO2Peak-VO2Rest)/VO2Rest]). The effects of training on insulin sensitivity (SI), inflammation and other metabolic syndrome features were examined. Results: Insulin action improved in response to training, as indicated by a ∼37% increase in SI (p =.018). Plasma levels of several proinflammatory cytokines were reduced in response to ET, as indicated by significant decrements in sTNF-R, CCL2, MPO, IL-6, resistin, and leptin, with no significant changes in hsCRP. ET induced reductions in BMI and percent total body fat. Conclusions: The present study supports the efficacy of ET interventions on metabolic syndrome features in morbidly obese minority youth. © 2013 Human Kinetics, Inc.

Authors
Many, G; Hurtado, M-E; Tanner, C; Houmard, J; Gordish-Dressman, H; Park, J-J; Uwaifo, G; Kraus, W; Hagberg, J; Hoffman, E
MLA Citation
Many, G, Hurtado, M-E, Tanner, C, Houmard, J, Gordish-Dressman, H, Park, J-J, Uwaifo, G, Kraus, W, Hagberg, J, and Hoffman, E. "Moderate-intensity aerobic training program improves insulin sensitivity and inflammatory markers in a pilot study of morbidly obese minority teens." Pediatric Exercise Science 25.1 (2013): 12-26.
PMID
23406700
Source
scival
Published In
Pediatric exercise science
Volume
25
Issue
1
Publish Date
2013
Start Page
12
End Page
26

Exercise training and implantable cardioverter-defibrillator shocks in patients with heart failure. Results from HF-ACTION (Heart failure and a controlled trial investigating outcomes of exercise training)

Objectives: The purpose of this study was to determine whether exercise training is associated with an increased risk of implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure (HF). Background: Few data are available regarding the safety of exercise training in patients with ICDs and HF. Methods: HF-ACTION (Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing) randomized 2,331 outpatients with HF and an ejection fraction (EF) ≤35% to exercise training or usual care. Cox proportional hazards modeling was used to examine the relationship between exercise training and ICD shocks. Results: We identified 1,053 patients (45%) with an ICD at baseline who were randomized to exercise training (n = 546) or usual care (n = 507). Median age was 61 years old, and median EF was 24%. Over a median of 2.2 years of follow-up, 20% (n = 108) of the exercise patients had a shock versus 22% (n = 113) of the control patients. A history of sustained ventricular tachycardia/fibrillation (hazard ratio [HR]: 1.93 [95% confidence interval (CI): 1.47 to 2.54]), previous atrial fibrillation/flutter (HR: 1.63 [95% CI: 1.22 to 2.18]), exercise-induced dysrhythmia (HR: 1.67 [95% CI: 1.23 to 2.26]), lower diastolic blood pressure (HR for 5-mm Hg decrease <60: 1.35 [95% CI: 1.12 to 1.61]), and nonwhite race (HR: 1.50 [95% CI: 1.13 to 2.00]) were associated with an increased risk of ICD shocks. Exercise training was not associated with the occurrence of ICD shocks (HR: 0.90 [95% CI: 0.69 to 1.18], p = 0.45). The presence of an ICD was not associated with the primary efficacy composite endpoint of death or hospitalization (HR: 0.99 [95% CI: 0.86 to 1.14], p = 0.90). Conclusions: We found no evidence of increased ICD shocks in patients with HF and reduced left ventricular function who underwent exercise training. Exercise therapy should not be prohibited in ICD recipients with HF. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437). © 2013 American College of Cardiology Foundation.

Authors
Piccini, JP; Hellkamp, AS; Whellan, DJ; Ellis, SJ; Keteyian, SJ; Kraus, WE; Hernandez, AF; Daubert, JP; Piña, IL; O'Connor, CM
MLA Citation
Piccini, JP, Hellkamp, AS, Whellan, DJ, Ellis, SJ, Keteyian, SJ, Kraus, WE, Hernandez, AF, Daubert, JP, Piña, IL, and O'Connor, CM. "Exercise training and implantable cardioverter-defibrillator shocks in patients with heart failure. Results from HF-ACTION (Heart failure and a controlled trial investigating outcomes of exercise training)." JACC: Heart Failure 1.2 (2013): 142-148.
PMID
23936756
Source
scival
Published In
JACC: Heart Failure
Volume
1
Issue
2
Publish Date
2013
Start Page
142
End Page
148
DOI
10.1016/j.jchf.2013.01.005

Association between hemoglobin level and cardiopulmonary performance in heart failure: Insights from the HF-ACTION study

Authors
Cohen-Solal, A; Keteyian, SJ; Horton, JR; Ellis, SJ; Kraus, WE; Kilpatrick, RD
MLA Citation
Cohen-Solal, A, Keteyian, SJ, Horton, JR, Ellis, SJ, Kraus, WE, and Kilpatrick, RD. "Association between hemoglobin level and cardiopulmonary performance in heart failure: Insights from the HF-ACTION study." International Journal of Cardiology (2013).
PMID
23735344
Source
scival
Published In
International Journal of Cardiology
Publish Date
2013
DOI
10.1016/j.ijcard.2013.05.070

Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.

Given the importance of cardiovascular disease (CVD) to public health and the demonstrated heritability of both disease status and its related risk factors, identifying the genetic variation underlying these susceptibilities is a critical step in understanding the pathogenesis of CVD and informing prevention and treatment strategies. Although one can look for genetic variation underlying susceptibility to CVD per se, it can be difficult to define the disease phenotype for such a qualitative analysis and CVD itself represents a convergence of diverse etiologic pathways. Alternatively, one can study the genetics of intermediate traits that are known risk factors for CVD, which can be measured quantitatively. Using the latter strategy, we have measured 21 cardiovascular-related biomarkers in an extended multigenerational pedigree, the CARRIAGE family (Carolinas Region Interaction of Aging, Genes, and Environment). These biomarkers belong to inflammatory and immune, connective tissue, lipid, and hemostasis pathways. Of these, 18 met our quality control standards. Using the pedigree and biomarker data, we have estimated the broad sense heritability (H2) of each biomarker (ranging from 0.09-0.56). A genome-wide panel of 6,015 SNPs was used subsequently to map these biomarkers as quantitative traits. Four showed noteworthy evidence for linkage in multipoint analysis (LOD score ≥ 2.6): paraoxonase (chromosome 8p11, 21), the chemokine RANTES (22q13.33), matrix metalloproteinase 3 (MMP3, 17p13.3), and granulocyte colony stimulating factor (GCSF, 8q22.1). Identifying the causal variation underlying each linkage score will help to unravel the genetic architecture of these quantitative traits and, by extension, the genetic architecture of cardiovascular risk.

Authors
Nolan, D; Kraus, WE; Hauser, E; Li, Y-J; Thompson, DK; Johnson, J; Chen, H-C; Nelson, S; Haynes, C; Gregory, SG; Kraus, VB; Shah, SH
MLA Citation
Nolan, D, Kraus, WE, Hauser, E, Li, Y-J, Thompson, DK, Johnson, J, Chen, H-C, Nelson, S, Haynes, C, Gregory, SG, Kraus, VB, and Shah, SH. "Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family. (Published online)" PLoS One 8.8 (2013): e71779-.
Website
http://hdl.handle.net/10161/10873
PMID
23936524
Source
pubmed
Published In
PloS one
Volume
8
Issue
8
Publish Date
2013
Start Page
e71779
DOI
10.1371/journal.pone.0071779

Caloric restriction: Implications for human cardiometabolic health

PURPOSE: While the impact of caloric restriction on human health is not fully understood, there is strong evidence to support further studies of its influence on cardiovascular health. The purpose of this review was to update the state of the science by examining the relevant literature regarding calorie-restriction effects on aging and cardiovascular health and to discuss the possible role(s) of calorie restriction in preserving cardiovascular function in humans. METHODS: For purpose of this review, we have defined calorie restriction as a reduction in energy intake well below the amount of calories that would be consumed ad libitum (≥10% in humans, ≥20% in animals). We examined the relevant literature on calorie-restriction effects on longevity and cardiovascular health, with an emphasis on the state of the science regarding calorie restriction in humans. We have emphasized the importance of the preliminary and expected findings from the Comprehensive Assessment of the Long-term Effect of Reducing Intake of Energy trial. RESULTS: Evidence from animal studies and a limited number of human trials indicates that calorie restriction has the potential to both delay cardiac aging and help prevent atherosclerotic cardiovascular disease via beneficial effects on blood pressure, lipids, inflammatory processes, and potentially other mechanisms. CONCLUSIONS: On the basis of its known benefits to cardiometabolic health, including modest calorie restriction in a combined lifestyle program is likely to improve heart health and prevent subsequent cardiovascular events in overweight and obese individuals. Additional study is needed to further illuminate its long-term applicability for older adults and for those with significant comorbidities, such as heart failure. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.

Authors
Bales, CW; Kraus, WE
MLA Citation
Bales, CW, and Kraus, WE. "Caloric restriction: Implications for human cardiometabolic health." Journal of Cardiopulmonary Rehabilitation and Prevention 33.4 (2013): 201-208.
PMID
23748374
Source
scival
Published In
Journal of Cardiopulmonary Rehabilitation and Prevention
Volume
33
Issue
4
Publish Date
2013
Start Page
201
End Page
208
DOI
10.1097/HCR.0b013e318295019e

Race, exercise training, and outcomes in chronic heart failure: Findings from Heart Failure - A Controlled Trial Investigating Outcomes in Exercise TraiNing (HF-ACTION)

Background: The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. Methods: We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. Results: There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P > .5). Conclusions: Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training. © 2013.

Authors
Mentz, RJ; Bittner, V; Schulte, PJ; Fleg, JL; Piña, IL; Keteyian, SJ; Moe, G; Nigam, A; Swank, AM; Onwuanyi, AE; al, E
MLA Citation
Mentz, RJ, Bittner, V, Schulte, PJ, Fleg, JL, Piña, IL, Keteyian, SJ, Moe, G, Nigam, A, Swank, AM, Onwuanyi, AE, and al, E. "Race, exercise training, and outcomes in chronic heart failure: Findings from Heart Failure - A Controlled Trial Investigating Outcomes in Exercise TraiNing (HF-ACTION)." American Heart Journal (2013).
PMID
24016498
Source
scival
Published In
American Heart Journal
Publish Date
2013
DOI
10.1016/j.ahj.2013.06.002

Association between resting heart rate, chronotropic index, and long-term outcomes in patients with heart failure receiving β-blocker therapy: Data from the HF-ACTION trial

AimsThe aim of this study was to assess the association between resting heart rate (HR), chronotropic index (CI), and clinical outcomes in optimally treated chronic heart failure (HF) patients on β-blocker therapy.Methods and resultsWe performed a sub-study in 1118 patients with HF and reduced ejection fraction (EF < 35%) included in the HF-ACTION trial. Patients in sinus rhythm who received a β-blocker and who performed with maximal effort on the exercise test were included. Chronotropic index was calculated as an index of HR reserve achieved, by using the equation (220-age) for estimating maximum HR. A sensitivity analysis using an equation developed for HF patients on β-blockers was also performed. Cox proportional hazards models were fit to assess the association between CI and clinical outcomes. Median (25th, 75th percentiles) follow-up was 32 (21, 44) months. In a multivariable model including resting HR and CI as continuous variables, neither was associated with the primary outcome of all-cause mortality or hospitalization. However, each 0.1 unit decrease in CI <0.6 was associated with 17% increased risk of all-cause mortality (hazard ratio 1.17, 95% confidence interval 1.01-1.36; P = 0.036), and 13% increased risk of cardiovascular mortality or HF hospitalization (hazard ratio 1.13, 1.02-1.26; P = 0.025). Overall, 666 of 1118 (60%) patients had a CI <0.6. Chronotropic index did not retain statistical significance when dichotomized at a value of ≤0.62.ConclusionIn HF patients receiving optimal medical therapy, a decrease in CI <0.6 was associated with adverse clinical outcomes. Obtaining an optimal HR response to exercise, even in patients receiving optimal β-blocker therapy, may be a therapeutic target in the HF population. © 2013 The Author.

Authors
Dobre, D; Zannad, F; Keteyian, SJ; Stevens, SR; Rossignol, P; Kitzman, DW; Landzberg, J; Howlett, J; Kraus, WE; Ellis, SJ
MLA Citation
Dobre, D, Zannad, F, Keteyian, SJ, Stevens, SR, Rossignol, P, Kitzman, DW, Landzberg, J, Howlett, J, Kraus, WE, and Ellis, SJ. "Association between resting heart rate, chronotropic index, and long-term outcomes in patients with heart failure receiving β-blocker therapy: Data from the HF-ACTION trial." European Heart Journal 34.29 (2013): 2271-2280.
PMID
23315907
Source
scival
Published In
European Heart Journal (Elsevier)
Volume
34
Issue
29
Publish Date
2013
Start Page
2271
End Page
2280
DOI
10.1093/eurheartj/ehs433

The genetic basis for survivorship in coronary artery disease.

Survivorship is a trait characterized by endurance and virility in the face of hardship. It is largely considered a psychosocial attribute developed during fatal conditions, rather than a biological trait for robustness in the context of complex, age-dependent diseases like coronary artery disease (CAD). The purpose of this paper is to present the novel phenotype, survivorship in CAD as an observed survival advantage concurrent with clinically significant CAD. We present a model for characterizing survivorship in CAD and its relationships with overlapping time- and clinically-related phenotypes. We offer an optimal measurement interval for investigating survivorship in CAD. We hypothesize genetic contributions to this construct and review the literature for evidence of genetic contribution to overlapping phenotypes in support of our hypothesis. We also present preliminary evidence of genetic effects on survival in people with clinically significant CAD from a primary case-control study of symptomatic coronary disease. Identifying gene variants that confer improved survival in the context of clinically appreciable CAD may improve our understanding of cardioprotective mechanisms acting at the gene level and potentially impact patients clinically in the future. Further, characterizing other survival-variant genetic effects may improve signal-to-noise ratio in detecting gene associations for CAD.

Authors
Dungan, JR; Hauser, ER; Qin, X; Kraus, WE
MLA Citation
Dungan, JR, Hauser, ER, Qin, X, and Kraus, WE. "The genetic basis for survivorship in coronary artery disease. (Published online)" Front Genet 4 (2013): 191-.
PMID
24143143
Source
pubmed
Published In
Front Genet
Volume
4
Publish Date
2013
Start Page
191
DOI
10.3389/fgene.2013.00191

Use of the Corus® CAD Gene Expression Test for Assessment of Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients

The determination of the underlying etiology of symptoms suggestive of obstructive coronary artery disease (CAD, ≥50% stenosis in a major coronary artery) is a common clinical challenge in both primary care and cardiology clinics. Usual care in low to medium risk patients often involves a family history, risk factor assessment, and then stress testing with or without non-invasive imaging. If positive, this is often followed by invasive coronary angiography (ICA). Despite extensive adoption of this usual care paradigm, more than 60% of patients referred for angiography do not have obstructive CAD. In order to robustly identify those symptomatic patients without obstructive CAD, who can avoid subsequent cardiac testing and look elsewhere for the cause of their symptoms, a recently described whole blood gene expression score (GES: Corus® CAD, CardioDx, Inc., Palo Alto, CA) has been developed and validated in two multi-center trials. This paper reviews the published literature and assessments by independent parties regarding the analytical and clinical validity as well as the clinical utility of the Corus® CAD test.

Authors
Vargas, J; Lima, JAC; Kraus, WE; Douglas, PS; Rosenberg, S
MLA Citation
Vargas, J, Lima, JAC, Kraus, WE, Douglas, PS, and Rosenberg, S. "Use of the Corus® CAD Gene Expression Test for Assessment of Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients." PLoS Currents AUG (2013).
Source
scival
Published In
PLoS Currents: Tree of Life
Issue
AUG
Publish Date
2013
DOI
10.1371/currents.eogt.0f04f6081905998fa92b99593478aeab

Race, exercise training, and outcomes in chronic heart failure: Findings from Heart Failure - A Controlled Trial Investigating Outcomes in Exercise TraiNing (HF-ACTION)

Background The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. Methods We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. Results There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P >.5). Conclusions Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training. © 2013 Mosby, Inc.

Authors
Mentz, RJ; Bittner, V; Schulte, PJ; Fleg, JL; Piña, IL; Keteyian, SJ; Moe, G; Nigam, A; Swank, AM; Onwuanyi, AE; Fitz-Gerald, M; Kao, A; Ellis, SJ; Kraus, WE; Whellan, DJ; O'Connor, CM
MLA Citation
Mentz, RJ, Bittner, V, Schulte, PJ, Fleg, JL, Piña, IL, Keteyian, SJ, Moe, G, Nigam, A, Swank, AM, Onwuanyi, AE, Fitz-Gerald, M, Kao, A, Ellis, SJ, Kraus, WE, Whellan, DJ, and O'Connor, CM. "Race, exercise training, and outcomes in chronic heart failure: Findings from Heart Failure - A Controlled Trial Investigating Outcomes in Exercise TraiNing (HF-ACTION)." American Heart Journal 166.3 (2013): 488-495.e1.
Source
scival
Published In
American Heart Journal
Volume
166
Issue
3
Publish Date
2013
Start Page
488
End Page
495.e1
DOI
10.1016/j.ahj.2013.06.002

Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults.

Recent guidelines on exercise for weight loss and weight maintenance include resistance training as part of the exercise prescription. Yet few studies have compared the effects of similar amounts of aerobic and resistance training on body mass and fat mass in overweight adults. STRRIDE AT/RT, a randomized trial, compared aerobic training, resistance training, and a combination of the two to determine the optimal mode of exercise for obesity reduction. Participants were 119 sedentary, overweight or obese adults who were randomized to one of three 8-mo exercise protocols: 1) RT: resistance training, 2) AT: aerobic training, and 3) AT/RT: aerobic and resistance training (combination of AT and RT). Primary outcomes included total body mass, fat mass, and lean body mass. The AT and AT/RT groups reduced total body mass and fat mass more than RT (P < 0.05), but they were not different from each other. RT and AT/RT increased lean body mass more than AT (P < 0.05). While requiring double the time commitment, a program of combined AT and RT did not result in significantly more fat mass or body mass reductions over AT alone. Balancing time commitments against health benefits, it appears that AT is the optimal mode of exercise for reducing fat mass and body mass, while a program including RT is needed for increasing lean mass in middle-aged, overweight/obese individuals.

Authors
Willis, LH; Slentz, CA; Bateman, LA; Shields, AT; Piner, LW; Bales, CW; Houmard, JA; Kraus, WE
MLA Citation
Willis, LH, Slentz, CA, Bateman, LA, Shields, AT, Piner, LW, Bales, CW, Houmard, JA, and Kraus, WE. "Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults." J Appl Physiol (1985) 113.12 (December 15, 2012): 1831-1837.
PMID
23019316
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
113
Issue
12
Publish Date
2012
Start Page
1831
End Page
1837
DOI
10.1152/japplphysiol.01370.2011

Elevated Galectin-3 Levels and Prediction of Mode of Death in Heart Failure: Insights from the HF-ACTION Study

Authors
Ahmad, T; Fiuzat, M; Stevens, S; Adams, KF; Whellan, DJ; Donahue, MP; Kitzman, DW; Pina, IL; Zannad, F; Kraus, WE; O'Connor, CM; Felker, GM
MLA Citation
Ahmad, T, Fiuzat, M, Stevens, S, Adams, KF, Whellan, DJ, Donahue, MP, Kitzman, DW, Pina, IL, Zannad, F, Kraus, WE, O'Connor, CM, and Felker, GM. "Elevated Galectin-3 Levels and Prediction of Mode of Death in Heart Failure: Insights from the HF-ACTION Study." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Integration of Whole Genome Methylation with Metabolomics Identifies Novel Cardiovascular Disease Genes

Authors
Shah, SH; Feng, S; Grass, E; Haynes, C; Chryst-Ladd, M; Craig, D; Hauser, ER; Newgard, CB; Kraus, WE; Gregory, SG
MLA Citation
Shah, SH, Feng, S, Grass, E, Haynes, C, Chryst-Ladd, M, Craig, D, Hauser, ER, Newgard, CB, Kraus, WE, and Gregory, SG. "Integration of Whole Genome Methylation with Metabolomics Identifies Novel Cardiovascular Disease Genes." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Genetic Variants in the Bone Morphogenic Protein (BMP) Family of Genes Interact with Mobile Source Air Pollution to Increase Risk of Peripheral Arterial Disease

Authors
Ward-Caviness, C; Neas, L; Haynes, C; Blach, C; Burns, E; LaRocque-Abramson, K; Dowdy, E; Casco, W; Devlin, R; Diaz-Sanchez, D; Kraus, WE; Shah, SH; Gregory, SG; Miranda, ML; Hauser, ER
MLA Citation
Ward-Caviness, C, Neas, L, Haynes, C, Blach, C, Burns, E, LaRocque-Abramson, K, Dowdy, E, Casco, W, Devlin, R, Diaz-Sanchez, D, Kraus, WE, Shah, SH, Gregory, SG, Miranda, ML, and Hauser, ER. "Genetic Variants in the Bone Morphogenic Protein (BMP) Family of Genes Interact with Mobile Source Air Pollution to Increase Risk of Peripheral Arterial Disease." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Association between Resting Heart Rate, Chronotropic Index and Long-term Outcomes in Patients with Heart Failure Receiving Beta-blocker Therapy. Data from the HF-ACTION Trial

Authors
Dobre, D; Zannad, F; Keteylan, SJ; Stevens, SR; Rossignol, P; Kitzman, DK; Landzberg, J; Howlett, J; Kraus, WE; Ellis, SJ
MLA Citation
Dobre, D, Zannad, F, Keteylan, SJ, Stevens, SR, Rossignol, P, Kitzman, DK, Landzberg, J, Howlett, J, Kraus, WE, and Ellis, SJ. "Association between Resting Heart Rate, Chronotropic Index and Long-term Outcomes in Patients with Heart Failure Receiving Beta-blocker Therapy. Data from the HF-ACTION Trial." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Race, Exercise Training and Outcomes in Chronic Heart Failure

Authors
Mentz, RJ; Bittner, V; Starr, AZ; Fleg, JL; Moe, G; Swank, AM; Fitz-Gerald, M; Nigam, A; Kao, A; Onwuanyi, A; Kraus, WE; Whellan, DJ; Ellis, SJ; O'Connor, CM
MLA Citation
Mentz, RJ, Bittner, V, Starr, AZ, Fleg, JL, Moe, G, Swank, AM, Fitz-Gerald, M, Nigam, A, Kao, A, Onwuanyi, A, Kraus, WE, Whellan, DJ, Ellis, SJ, and O'Connor, CM. "Race, Exercise Training and Outcomes in Chronic Heart Failure." CIRCULATION 126.21 (November 20, 2012).
Source
wos-lite
Published In
Circulation
Volume
126
Issue
21
Publish Date
2012

Relation between volume of exercise and clinical outcomes in patients with heart failure.

OBJECTIVES: This study determined whether greater volumes of exercise were associated with greater reductions in clinical events. BACKGROUND: The HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial showed that among patients with heart failure (HF), regular exercise confers a modest reduction in the adjusted risk for all-cause mortality or hospitalization. METHODS: Patients randomized to the exercise training arm of HF-ACTION who were event-free at 3 months after randomization were included (n = 959). Median follow-up was 28.2 months. Clinical endpoints were all-cause mortality or hospitalization and cardiovascular mortality or HF hospitalization. RESULTS: A reverse J-shaped association was observed between exercise volume and adjusted clinical risk. On the basis of Cox regression, exercise volume was not a significant linear predictor but was a logarithmic predictor (p = 0.03) for all-cause mortality or hospitalization. For cardiovascular mortality or HF hospitalization, exercise volume was a significant (p = 0.001) linear and logarithmic predictor. Moderate exercise volumes of 3 to <5 metabolic equivalent (MET)-h and 5 to <7 MET-h per week were associated with reductions in subsequent risk that exceeded 30%. Exercise volume was positively associated with the change in peak oxygen uptake at 3 months (r = 0.10; p = 0.005). CONCLUSIONS: In patients with chronic systolic HF, volume of exercise is associated with the risk for clinical events, with only moderate levels (3 to 7 MET-h per week) of exercise needed to observe a clinical benefit. Although further study is warranted to confirm the relationship between volume of exercise completed and clinical events, our findings support the use of regular exercise in the management of these patients.

Authors
Keteyian, SJ; Leifer, ES; Houston-Miller, N; Kraus, WE; Brawner, CA; O'Connor, CM; Whellan, DJ; Cooper, LS; Fleg, JL; Kitzman, DW; Cohen-Solal, A; Blumenthal, JA; Rendall, DS; Piña, IL; HF-ACTION Investigators,
MLA Citation
Keteyian, SJ, Leifer, ES, Houston-Miller, N, Kraus, WE, Brawner, CA, O'Connor, CM, Whellan, DJ, Cooper, LS, Fleg, JL, Kitzman, DW, Cohen-Solal, A, Blumenthal, JA, Rendall, DS, Piña, IL, and HF-ACTION Investigators, . "Relation between volume of exercise and clinical outcomes in patients with heart failure." J Am Coll Cardiol 60.19 (November 6, 2012): 1899-1905.
PMID
23062530
Source
pubmed
Published In
Journal of the American College of Cardiology
Volume
60
Issue
19
Publish Date
2012
Start Page
1899
End Page
1905
DOI
10.1016/j.jacc.2012.08.958

In-hospital resource use and medical costs in the last year of life by mode of death (from the HF-ACTION randomized controlled trial).

Patterns of medical resource use near the end of life may differ across modes of death. The aim of this study was to characterize patterns of inpatient resource use and direct costs for patients with heart failure (HF) who died of sudden cardiac death (SCD), HF, other cardiovascular causes, or noncardiovascular causes during the last year of life. Data were from a randomized trial of exercise training in patients with HF. Mode of death was adjudicated by an end point committee. Generalized estimating equations were used to compare hospitalizations, inpatient days, and inpatient costs incurred during the final year of life in patients who died of different causes, adjusting for clinical and treatment characteristics. Of 2,331 patients enrolled in the trial, 231 died after ≥1 year of follow-up with an adjudicated mode of death, including 72 of SCD, 80 of HF, 34 of other cardiovascular causes, and 45 of noncardiovascular causes. Patients who died of SCD were younger, had less severe HF, and incurred fewer hospitalizations, fewer inpatient days, and lower inpatient costs than patients who died of other causes. After adjustment for patient characteristics, inpatient resource use varied by 2 to 4 times across modes of death, suggesting that cost-effectiveness analyses of interventions that reduce mortality from SCD compared to other causes should incorporate mode-specific end-of-life costs. In conclusion, resource use and associated medical costs in the last year of life differed markedly in patients with HF who experienced SCD and patients who died of other causes.

Authors
Reed, SD; Li, Y; Dunlap, ME; Kraus, WE; Samsa, GP; Schulman, KA; Zile, MR; Whellan, DJ
MLA Citation
Reed, SD, Li, Y, Dunlap, ME, Kraus, WE, Samsa, GP, Schulman, KA, Zile, MR, and Whellan, DJ. "In-hospital resource use and medical costs in the last year of life by mode of death (from the HF-ACTION randomized controlled trial)." Am J Cardiol 110.8 (October 15, 2012): 1150-1155.
PMID
22762718
Source
pubmed
Published In
American Journal of Cardiology
Volume
110
Issue
8
Publish Date
2012
Start Page
1150
End Page
1155
DOI
10.1016/j.amjcard.2012.05.059

Aerobic and resistance training effects on energy intake: the STRRIDE-AT/RT study.

PURPOSE: Our study characterizes food and energy intake responses to long-term aerobic training (AT) and resistance training (RT) during a controlled 8-month trial. METHODS: In the STRRIDE-AT/RT trial, overweight/obese sedentary dyslipidemic men and women were randomized to AT (n = 39), RT (n = 38), or a combined treatment (AT/RT, n = 40) without any advice to change their food intakes. Quantitative food intake assessments and food frequency questionnaires were collected at baseline (before training) and after 8 months of training (end of training); body mass (BM) and fat-free mass (FFM) were also assessed. RESULTS: In AT and AT/RT, respectively, meaningful decreases in reported energy intake (REI) (-217 and -202 kcal, P < 0.001) and in intakes of fat (-14.9 and -14.9 g, P < 0.001, P = 0.004), protein (-8.3 and -10.7 g, P = 0.002, P < 0.001), and carbohydrate (-28.1 and -14.7 g, P = 0.001, P = 0.030) were found by food frequency questionnaires. REI relative to FFM decreased (P < 0.001 and P = 0.002), as did intakes of fat (-0.2 and -0.3 g, P = 0.003 and P = 0.014) and protein (-0.1 and -0.2 g, P = 0.005 and P < 0.001) in AT and AT/RT and carbohydrate (-0.5 g, P < 0.003) in AT only. For RT, REI by quantitative daily dietary intake decreased (-3.0 kcal.kg(-1) FFM, P = 0.046), as did fat intake (-0.2 g, P = 0.033). BM decreased in AT (-1.3 kg, P = 0.006) and AT/RT (-1.5 kg, P = 0.001) but was unchanged (0.6 kg, P = 0.176) in RT. CONCLUSIONS: Previously sedentary subjects completing 8 months of AT or AT/RT reduced their intakes of calories and macronutrients and BM. In RT, fat intakes and REI (when expressed per FFM) decreased, BM was unchanged, and FFM increased.

Authors
Bales, CW; Hawk, VH; Granville, EO; Rose, SB; Shields, T; Bateman, L; Willis, L; Piner, LW; Slentz, CA; Houmard, JA; Gallup, D; Samsa, GP; Kraus, WE
MLA Citation
Bales, CW, Hawk, VH, Granville, EO, Rose, SB, Shields, T, Bateman, L, Willis, L, Piner, LW, Slentz, CA, Houmard, JA, Gallup, D, Samsa, GP, and Kraus, WE. "Aerobic and resistance training effects on energy intake: the STRRIDE-AT/RT study." Med Sci Sports Exerc 44.10 (October 2012): 2033-2039.
PMID
22525775
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
44
Issue
10
Publish Date
2012
Start Page
2033
End Page
2039
DOI
10.1249/MSS.0b013e318259479a

Contributions of Inflammation, Inactivity, and Low Dose Prednisone Use to Skeletal Muscle Insulin Resistance in Well-Controlled Rheumatoid Arthritis

Authors
Abouassi, H; Bateman, L; McDaniel, GE; Elliott-Penry, L; Muehlbauer, M; St Clair, EW; Kraus, WE; Huffman, KM
MLA Citation
Abouassi, H, Bateman, L, McDaniel, GE, Elliott-Penry, L, Muehlbauer, M, St Clair, EW, Kraus, WE, and Huffman, KM. "Contributions of Inflammation, Inactivity, and Low Dose Prednisone Use to Skeletal Muscle Insulin Resistance in Well-Controlled Rheumatoid Arthritis." October 2012.
Source
wos-lite
Published In
Arthritis and Rheumatism
Volume
64
Issue
10
Publish Date
2012
Start Page
S525
End Page
S525

Knee Osteoarthritis and Serum Uric Acid Concentration: The Third National Health and Examination Survey

Authors
Ning, T; Pieper, C; Kraus, VB; Kraus, WE; Huffman, KM
MLA Citation
Ning, T, Pieper, C, Kraus, VB, Kraus, WE, and Huffman, KM. "Knee Osteoarthritis and Serum Uric Acid Concentration: The Third National Health and Examination Survey." October 2012.
Source
wos-lite
Published In
Arthritis and Rheumatism
Volume
64
Issue
10
Publish Date
2012
Start Page
S116
End Page
S116

Metabolomic profiling for the identification of novel biomarkers and mechanisms related to common cardiovascular diseases: form and function.

Authors
Shah, SH; Kraus, WE; Newgard, CB
MLA Citation
Shah, SH, Kraus, WE, and Newgard, CB. "Metabolomic profiling for the identification of novel biomarkers and mechanisms related to common cardiovascular diseases: form and function." Circulation 126.9 (August 28, 2012): 1110-1120. (Review)
PMID
22927473
Source
pubmed
Published In
Circulation
Volume
126
Issue
9
Publish Date
2012
Start Page
1110
End Page
1120
DOI
10.1161/CIRCULATIONAHA.111.060368

Effects of exercise training on depressive symptoms in patients with chronic heart failure: the HF-ACTION randomized trial.

CONTEXT: Depression is common in patients with cardiac disease, especially in patients with heart failure, and is associated with increased risk of adverse health outcomes. Some evidence suggests that aerobic exercise may reduce depressive symptoms, but to our knowledge the effects of exercise on depression in patients with heart failure have not been evaluated. OBJECTIVE: To determine whether exercise training will result in greater improvements in depressive symptoms compared with usual care among patients with heart failure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial involving 2322 stable patients treated for heart failure at 82 medical clinical centers in the United States, Canada, and France. Patients who had a left ventricular ejection fraction of 35% or lower, had New York Heart Association class I to IV heart failure, and had completed the Beck Depression Inventory II (BDI-II) score were randomized (1:1) between April 2003 and February 2007. Depressive scores ranged from 0 to 59; scores of 14 or higher are considered clinically significant. INTERVENTIONS: Participants were randomized either to supervised aerobic exercise (goal of 90 min/wk for months 1-3 followed by home exercise with a goal of ≥120 min/wk for months 4-12) or to education and usual guideline-based heart failure care. MAIN OUTCOME MEASURES: Composite of death or hospitalization due to any cause and scores on the BDI-II at months 3 and 12. RESULTS: Over a median follow-up period of 30 months, 789 patients (68%) died or were hospitalized in the usual care group compared with 759 (66%) in the aerobic exercise group (hazard ratio [HR], 0.89; 95% CI, 0.81 to 0.99; P = .03). The median BDI-II score at study entry was 8, with 28% of the sample having BDI-II scores of 14 or higher. Compared with usual care, aerobic exercise resulted in lower mean BDI-II scores at 3 months (aerobic exercise, 8.95; 95% CI, 8.61 to 9.29 vs usual care, 9.70; 95% CI, 9.34 to 10.06; difference, -0.76; 95% CI,-1.22 to -0.29; P = .002) and at 12 months (aerobic exercise, 8.86; 95% CI, 8.67 to 9.24 vs usual care, 9.54; 95% CI, 9.15 to 9.92; difference, -0.68; 95% CI, -1.20 to -0.16; P = .01). CONCLUSIONS: Compared with guideline-based usual care, exercise training resulted in a modest reduction in depressive symptoms, although the clinical significance of this improvement is unknown. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00047437.

Authors
Blumenthal, JA; Babyak, MA; O'Connor, C; Keteyian, S; Landzberg, J; Howlett, J; Kraus, W; Gottlieb, S; Blackburn, G; Swank, A; Whellan, DJ
MLA Citation
Blumenthal, JA, Babyak, MA, O'Connor, C, Keteyian, S, Landzberg, J, Howlett, J, Kraus, W, Gottlieb, S, Blackburn, G, Swank, A, and Whellan, DJ. "Effects of exercise training on depressive symptoms in patients with chronic heart failure: the HF-ACTION randomized trial." JAMA 308.5 (August 1, 2012): 465-474.
PMID
22851113
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
308
Issue
5
Publish Date
2012
Start Page
465
End Page
474
DOI
10.1001/jama.2012.8720

Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial.

OBJECTIVES: This study sought to examine the association between baseline beta-blocker (BB) dose and outcomes in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial. BACKGROUND: Beta-blockers reduce morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction, but it is unclear whether titrating to higher BB doses improves outcomes in this setting. METHODS: The HF-ACTION trial was a randomized, multicenter trial enrolling 2,331 ambulatory HF patients with systolic dysfunction (New York Heart Association functional class II to IV, left ventricular ejection fraction <0.35) randomized to exercise training versus usual care, with median follow-up of 2.5 years. The BB dose at baseline was standardized with carvedilol equivalents and analyzed as a continuous variable and by discrete dose groups. The relationship between BB dose and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints was determined before and after adjustment for variables significantly associated with outcomes in the HF-ACTION cohort. RESULTS: Ninety-five percent of patients were receiving a BB. There was a significant inverse relationship between BB dose and all-cause death or hospitalization but not other cardiovascular endpoints after adjustment for other predictors of outcome, with a linear benefit up to the 50-mg daily dose. There was a significant association between BB dose and change in peak VO(2) at 3 months. There was no increase in bradycardia with higher doses of BB. CONCLUSIONS: There was a significant inverse relationship between BB dose and the endpoint of all-cause death or all-cause hospitalization in this well-treated HF cohort with systolic dysfunction, supporting recommendations that titrating doses up to 50 mg/day might confer a benefit in such patients. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Authors
Fiuzat, M; Wojdyla, D; Kitzman, D; Fleg, J; Keteyian, SJ; Kraus, WE; Piña, IL; Whellan, D; O'Connor, CM
MLA Citation
Fiuzat, M, Wojdyla, D, Kitzman, D, Fleg, J, Keteyian, SJ, Kraus, WE, Piña, IL, Whellan, D, and O'Connor, CM. "Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial." J Am Coll Cardiol 60.3 (July 17, 2012): 208-215.
PMID
22560018
Source
pubmed
Published In
Journal of the American College of Cardiology
Volume
60
Issue
3
Publish Date
2012
Start Page
208
End Page
215
DOI
10.1016/j.jacc.2012.03.023

The Effects of Aerobic Training on Markers of Systemic Inflammation in Extremely Obese Minority Teens

Authors
Many, GM; Hurtado, M-E; Park, J-J; Spurney, CF; Rhee, LQ; Nunez, SB; Hagberg, JM; Uwaifo, GI; Kraus, WE; Houmard, JA; Damsker, JM; Tanner, CJ; Rakhmanina, N; Janicic, N; Hoffman, EP
MLA Citation
Many, GM, Hurtado, M-E, Park, J-J, Spurney, CF, Rhee, LQ, Nunez, SB, Hagberg, JM, Uwaifo, GI, Kraus, WE, Houmard, JA, Damsker, JM, Tanner, CJ, Rakhmanina, N, Janicic, N, and Hoffman, EP. "The Effects of Aerobic Training on Markers of Systemic Inflammation in Extremely Obese Minority Teens." JOURNAL OF GENERAL INTERNAL MEDICINE 27 (July 2012): 683-684.
Source
wos-lite
Published In
Journal of General Internal Medicine
Volume
27
Publish Date
2012
Start Page
683
End Page
684

Multiplex Profiling Demonstrates That Circulating Adipokines Are Related To Insulin Sensitivity But Not BMI

Authors
Pierce, JR; Kraus, RM; Houmard, JA; Kraus, WE; Tanner, CJ; Choi, MD; Hickner, RC
MLA Citation
Pierce, JR, Kraus, RM, Houmard, JA, Kraus, WE, Tanner, CJ, Choi, MD, and Hickner, RC. "Multiplex Profiling Demonstrates That Circulating Adipokines Are Related To Insulin Sensitivity But Not BMI." JOURNAL OF GENERAL INTERNAL MEDICINE 27 (July 2012): 482-482.
Source
wos-lite
Published In
Journal of General Internal Medicine
Volume
27
Publish Date
2012
Start Page
482
End Page
482

Exercise effects on lipids in persons with varying dietary patterns-does diet matter if they exercise? Responses in Studies of a Targeted Risk Reduction Intervention through Defined Exercise I.

BACKGROUND: The standard clinical approach for reducing cardiovascular disease risk due to dyslipidemia is to prescribe changes in diet and physical activity. The purpose of the current study was to determine if, across a range of dietary patterns, there were variable lipoprotein responses to an aerobic exercise training intervention. METHODS: Subjects were participants in the STRRIDE I, a supervised exercise program in sedentary, overweight subjects randomized to 6 months of inactivity or 1 of 3 aerobic exercise programs. To characterize diet patterns observed during the study, we calculated a modified z-score that included intakes of total fat, saturated fat, trans fatty acids, cholesterol, omega-3 fatty acids, and fiber as compared with the 2006 American Heart Association diet recommendations. Linear models were used to evaluate relationships between diet patterns and exercise effects on lipoproteins/lipids. RESULTS: Independent of diet, exercise had beneficial effects on low-density lipoprotein cholesterol particle number, low-density lipoprotein cholesterol size, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol size, and triglycerides (P < .05 for all). However, having a diet pattern that closely adhered to American Heart Association recommendations was not related to changes in these or any other serum lipids or lipoproteins in any of the exercise groups. CONCLUSIONS: We found that even in sedentary individuals whose habitual diets vary in the extent of adherence to AHA dietary recommendations, a rigorous, supervised exercise intervention can achieve significant beneficial lipid effects.

Authors
Huffman, KM; Hawk, VH; Henes, ST; Ocampo, CI; Orenduff, MC; Slentz, CA; Johnson, JL; Houmard, JA; Samsa, GP; Kraus, WE; Bales, CW
MLA Citation
Huffman, KM, Hawk, VH, Henes, ST, Ocampo, CI, Orenduff, MC, Slentz, CA, Johnson, JL, Houmard, JA, Samsa, GP, Kraus, WE, and Bales, CW. "Exercise effects on lipids in persons with varying dietary patterns-does diet matter if they exercise? Responses in Studies of a Targeted Risk Reduction Intervention through Defined Exercise I." Am Heart J 164.1 (July 2012): 117-124.
PMID
22795291
Source
pubmed
Published In
American Heart Journal
Volume
164
Issue
1
Publish Date
2012
Start Page
117
End Page
124
DOI
10.1016/j.ahj.2012.04.014

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.

The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance. By converting acetyl-CoA to its membrane permeant acetylcarnitine ester, CrAT regulates mitochondrial and intracellular carbon trafficking. Studies in muscle-specific Crat knockout mice, primary human skeletal myocytes, and human subjects undergoing L-carnitine supplementation support a model wherein CrAT combats nutrient stress, promotes metabolic flexibility, and enhances insulin action by permitting mitochondrial efflux of excess acetyl moieties that otherwise inhibit key regulatory enzymes such as pyruvate dehydrogenase. These findings offer therapeutically relevant insights into the molecular basis of metabolic inflexibility.

Authors
Muoio, DM; Noland, RC; Kovalik, J-P; Seiler, SE; Davies, MN; DeBalsi, KL; Ilkayeva, OR; Stevens, RD; Kheterpal, I; Zhang, J; Covington, JD; Bajpeyi, S; Ravussin, E; Kraus, W; Koves, TR; Mynatt, RL
MLA Citation
Muoio, DM, Noland, RC, Kovalik, J-P, Seiler, SE, Davies, MN, DeBalsi, KL, Ilkayeva, OR, Stevens, RD, Kheterpal, I, Zhang, J, Covington, JD, Bajpeyi, S, Ravussin, E, Kraus, W, Koves, TR, and Mynatt, RL. "Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility." Cell Metab 15.5 (May 2, 2012): 764-777.
PMID
22560225
Source
pubmed
Published In
Cell Metabolism
Volume
15
Issue
5
Publish Date
2012
Start Page
764
End Page
777
DOI
10.1016/j.cmet.2012.04.005

Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease.

BACKGROUND: Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk. METHODS: We studied 2,023 consecutive patients undergoing cardiac catheterization. Mass spectrometry profiling of 69 metabolites and lipid assessments were performed in fasting plasma. Principal component analysis reduced metabolites to a smaller number of uncorrelated factors. Independent relationships between factors and time-to-clinical events were assessed using Cox modeling. Clinical and metabolomic models were compared using log-likelihood and reclassification analyses. RESULTS: At median follow-up of 3.1 years, there were 232 deaths and 294 death/myocardial infarction (MI) events. Five of 13 metabolite factors were independently associated with mortality: factor 1 (medium-chain acylcarnitines: hazard ratio [HR] 1.12 [95% CI, 1.04-1.21], P = .005), factor 2 (short-chain dicarboxylacylcarnitines: HR 1.17 [1.05-1.31], P = .005), factor 3 (long-chain dicarboxylacylcarnitines: HR 1.14 [1.05-1.25], P = .002); factor 6 (branched-chain amino acids: HR 0.86 [0.75-0.99], P = .03), and factor 12 (fatty acids: HR 1.19 [1.06-1.35], P = .004). Three factors independently predicted death/MI: factor 2 (HR 1.11 [1.01-1.23], P = .04), factor 3 (HR 1.13 [1.04-1.22], P = .005), and factor 12 (HR 1.18 [1.05-1.32], P = .004). For mortality, 27% of intermediate-risk patients were correctly reclassified (net reclassification improvement 8.8%, integrated discrimination index 0.017); for death/MI model, 11% were correctly reclassified (net reclassification improvement 3.9%, integrated discrimination index 0.012). CONCLUSIONS: Metabolic profiles predict cardiovascular events independently of standard predictors.

Authors
Shah, SH; Sun, J-L; Stevens, RD; Bain, JR; Muehlbauer, MJ; Pieper, KS; Haynes, C; Hauser, ER; Kraus, WE; Granger, CB; Newgard, CB; Califf, RM; Newby, LK
MLA Citation
Shah, SH, Sun, J-L, Stevens, RD, Bain, JR, Muehlbauer, MJ, Pieper, KS, Haynes, C, Hauser, ER, Kraus, WE, Granger, CB, Newgard, CB, Califf, RM, and Newby, LK. "Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease." Am Heart J 163.5 (May 2012): 844-850.e1.
PMID
22607863
Source
pubmed
Published In
American Heart Journal
Volume
163
Issue
5
Publish Date
2012
Start Page
844
End Page
850.e1
DOI
10.1016/j.ahj.2012.02.005

Functional Outcomes of Exercise Progression Models in the Elderly

Authors
Allen, JD; Robbins, JL; Johanssen, N; VanBruggen, M; Credeur, D; Hollis, B; Johnson, JL; Church, T; Kraus, WE; Ravussin, E; Earnest, C; Ham, KL; Pieper, C; Welsch, MA
MLA Citation
Allen, JD, Robbins, JL, Johanssen, N, VanBruggen, M, Credeur, D, Hollis, B, Johnson, JL, Church, T, Kraus, WE, Ravussin, E, Earnest, C, Ham, KL, Pieper, C, and Welsch, MA. "Functional Outcomes of Exercise Progression Models in the Elderly." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 44 (May 2012): 821-821.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
44
Publish Date
2012
Start Page
821
End Page
821

Changes in Peripheral and Central Blood Pressure following Regional Specific Exercise

Authors
VanBruggen, M; Credeur, D; Ham, KL; Earnest, C; Robbins, JL; Johannsen, N; Kraus, WE; Church, TS; Ravussin, E; Welsch, MA; Allen, JD
MLA Citation
VanBruggen, M, Credeur, D, Ham, KL, Earnest, C, Robbins, JL, Johannsen, N, Kraus, WE, Church, TS, Ravussin, E, Welsch, MA, and Allen, JD. "Changes in Peripheral and Central Blood Pressure following Regional Specific Exercise." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 44 (May 2012): 99-99.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
44
Publish Date
2012
Start Page
99
End Page
99

The Relation Between The Blodd Pressure Response To Exercise During Training And Detraining Periods

Authors
Moker, EA; Bateman, LA; Kraus, WE; Pescatello, LS
MLA Citation
Moker, EA, Bateman, LA, Kraus, WE, and Pescatello, LS. "The Relation Between The Blodd Pressure Response To Exercise During Training And Detraining Periods." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 44 (May 2012): 393-393.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
44
Publish Date
2012
Start Page
393
End Page
393

Metabolic profiles predict adverse events after coronary artery bypass grafting.

OBJECTIVE: Clinical models incompletely predict the outcomes after coronary artery bypass grafting. Novel molecular technologies can identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. METHODS: The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected before surgery. Principal components analysis and Cox proportional hazards regression modeling were used to assess the relation between the metabolite factor levels and a composite outcome of postcoronary artery bypass grafting myocardial infarction, the need for percutaneous coronary intervention, repeat coronary artery bypass grafting, and death. RESULTS: During a mean follow-up period of 4.3 ± 2.4 years, 126 subjects (26.4%) experienced an adverse event. Three principal components analysis-derived factors were significantly associated with an adverse outcome on univariate analysis: short-chain dicarboxylacylcarnitines (factor 2, P = .001); ketone-related metabolites (factor 5, P = .02); and short-chain acylcarnitines (factor 6, P = .004). These 3 factors remained independently predictive of an adverse outcome after multivariate adjustment: factor 2 (adjusted hazard ratio, 1.23; 95% confidence interval, 1.10-1.38; P < .001), factor 5 (odds ratio, 1.17; 95% confidence interval, 1.01-1.37; P = .04), and factor 6 (odds ratio, 1.14; 95% confidence interval, 1.02-1.27; P = .03). CONCLUSIONS: Metabolic profiles are independently associated with adverse outcomes after coronary artery bypass grafting. These profiles might represent novel biomarkers of risk that can augment existing tools for risk stratification of coronary artery bypass grafting patients and might elucidate novel biochemical pathways that mediate risk.

Authors
Shah, AA; Craig, DM; Sebek, JK; Haynes, C; Stevens, RC; Muehlbauer, MJ; Granger, CB; Hauser, ER; Newby, LK; Newgard, CB; Kraus, WE; Hughes, GC; Shah, SH
MLA Citation
Shah, AA, Craig, DM, Sebek, JK, Haynes, C, Stevens, RC, Muehlbauer, MJ, Granger, CB, Hauser, ER, Newby, LK, Newgard, CB, Kraus, WE, Hughes, GC, and Shah, SH. "Metabolic profiles predict adverse events after coronary artery bypass grafting." J Thorac Cardiovasc Surg 143.4 (April 2012): 873-878.
PMID
22306227
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
143
Issue
4
Publish Date
2012
Start Page
873
End Page
878
DOI
10.1016/j.jtcvs.2011.09.070

Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training.

The aims of this study were twofold: (1) to identify whether peripheral artery disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A, anti-angiogenic VEGF₁₆₅b or VEGF receptor 1 (VEGF-R1) when compared with control subjects, and (2) to evaluate whether exercise training in PAD patients was associated with changes in muscle concentration of VEGF-A, VEGF₁₆₅b or VEGF-R1. At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle biopsy. Twelve PAD patients were treated with supervised exercise training (SET) and underwent muscle biopsy after 3 weeks and 12 weeks of training and had sufficient tissue to measure VEGF-A, VEGF₁₆₅b and VEGF-R1 concentrations in skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF₁₆₅b were similar in PAD patients versus controls at baseline. At both time points after the start of SET, VEGF-A levels decreased and there was a trend towards increased VEGF₁₆₅b concentrations. At baseline, VEGF-R1 concentrations were lower in PAD patients when compared with controls but did not change after SET. Skeletal muscle concentrations of VEGF-A are not different in PAD patients when compared with controls at baseline. SET is associated with a significant reduction in VEGF-A levels and a trend towards increased VEGF₁₆₅b levels. These somewhat unexpected findings suggest that further investigation into the mechanism of vascular responses to exercise training in PAD patients is warranted.

Authors
Jones, WS; Duscha, BD; Robbins, JL; Duggan, NN; Regensteiner, JG; Kraus, WE; Hiatt, WR; Dokun, AO; Annex, BH
MLA Citation
Jones, WS, Duscha, BD, Robbins, JL, Duggan, NN, Regensteiner, JG, Kraus, WE, Hiatt, WR, Dokun, AO, and Annex, BH. "Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training." Vasc Med 17.2 (April 2012): 94-100.
PMID
22402934
Source
pubmed
Published In
Vascular Medicine
Volume
17
Issue
2
Publish Date
2012
Start Page
94
End Page
100
DOI
10.1177/1358863X11436334

A PERIPHERAL BLOOD GENE EXPRESSION SCORE FOR CORONARY ARTERY DISEASE IN NON-DIABETIC PATIENTS IDENTIFIES PATIENTS AT LOW RISK FOR MAJOR CARDIOVASCULAR EVENTS AND INTERVENTIONAL PROCEDURES IN THE NEXT 12 MONTHS

Authors
Kraus, WE; Voros, S; Schwartz, RS; Ellis, S; Waksman, R; Tahirkheli, N; Lieu, H; Elashoff, MR; Rosenberg, S; McPherson, J; Lansky, A; Topol, E
MLA Citation
Kraus, WE, Voros, S, Schwartz, RS, Ellis, S, Waksman, R, Tahirkheli, N, Lieu, H, Elashoff, MR, Rosenberg, S, McPherson, J, Lansky, A, and Topol, E. "A PERIPHERAL BLOOD GENE EXPRESSION SCORE FOR CORONARY ARTERY DISEASE IN NON-DIABETIC PATIENTS IDENTIFIES PATIENTS AT LOW RISK FOR MAJOR CARDIOVASCULAR EVENTS AND INTERVENTIONAL PROCEDURES IN THE NEXT 12 MONTHS." March 27, 2012.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
59
Issue
13
Publish Date
2012
Start Page
E1383
End Page
E1383

Exercise dose response in muscle.

Exercise increases peak VO2 partially through muscle adaptations. However, understanding muscle adaptations related to exercise dose is incomplete. This study investigated exercise training dose on capillaries per fiber and capillaries per area; and citrate synthase from vastus lateralis and related both to changes in peak VO2. This randomized trial compared 3 exercise doses: low amount-moderate intensity (n=40), low amount-high intensity (n=47), high amount-high intensity (n=41), and a control group (n=35). Both measures of capillary supply increased in all exercise groups (p<0.05). Low amount-high intensity and high amount-high intensity improved citrate synthase (p<0.05) and the low amount-moderate intensity citrate synthase approached significance (p=0.059). Muscle improvements were only related to improvements in peak VO2 in high amount-high intensity (citrate synthase, r=0.304; capillaries:fiber, r= - 0.318; p<0.05 and capillaries/mm2 r= - 0.310, p<0.05). These data suggest muscle adaptations occur following both low and high exercise doses, but are only related to improved peak VO2 following high amount-high intensity training.

Authors
Duscha, BD; Annex, BH; Johnson, JL; Huffman, K; Houmard, J; Kraus, WE
MLA Citation
Duscha, BD, Annex, BH, Johnson, JL, Huffman, K, Houmard, J, and Kraus, WE. "Exercise dose response in muscle." International journal of sports medicine 33.3 (March 2012): 218-223.
PMID
22261824
Source
epmc
Published In
International Journal of Sports Medicine
Volume
33
Issue
3
Publish Date
2012
Start Page
218
End Page
223
DOI
10.1055/s-0031-1291323

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5.

BACKGROUND: Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas). RESULTS: We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604, p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003. CONCLUSION: Using an intermediate disease-related quantitative trait of LDL-C we have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These four genes should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.

Authors
Nolan, DK; Sutton, B; Haynes, C; Johnson, J; Sebek, J; Dowdy, E; Crosslin, D; Crossman, D; Sketch, MH; Granger, CB; Seo, D; Goldschmidt-Clermont, P; Kraus, WE; Gregory, SG; Hauser, ER; Shah, SH
MLA Citation
Nolan, DK, Sutton, B, Haynes, C, Johnson, J, Sebek, J, Dowdy, E, Crosslin, D, Crossman, D, Sketch, MH, Granger, CB, Seo, D, Goldschmidt-Clermont, P, Kraus, WE, Gregory, SG, Hauser, ER, and Shah, SH. "Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5. (Published online)" BMC Genet 13 (February 27, 2012): 12-.
PMID
22369142
Source
pubmed
Published In
BMC Genetics
Volume
13
Publish Date
2012
Start Page
12
DOI
10.1186/1471-2156-13-12

Factors related to morbidity and mortality in patients with chronic heart failure with systolic dysfunction: the HF-ACTION predictive risk score model.

BACKGROUND: We aimed to develop a multivariable statistical model for risk stratification in patients with chronic heart failure with systolic dysfunction, using patient data that are routinely collected and easily obtained at the time of initial presentation. METHODS AND RESULTS: In a cohort of 2331 patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing) study (New York Heart Association class II-IV, left ventricular ejection fraction ≤0.35, randomized to exercise training and usual care versus usual care alone, median follow-up of 2.5 years), we performed risk modeling using Cox proportional hazards models and analyzed the relationship between baseline clinical factors and the primary composite end point of death or all-cause hospitalization and the secondary end point of all-cause death alone. Prognostic relationships for continuous variables were examined using restricted cubic spline functions, and key predictors were identified using a backward variable selection process and bootstrapping methods. For ease of use in clinical practice, point-based risk scores were developed from the risk models. Exercise duration on the baseline cardiopulmonary exercise test was the most important predictor of both the primary end point and all-cause death. Additional important predictors for the primary end point risk model (in descending strength) were Kansas City Cardiomyopathy Questionnaire symptom stability score, higher serum urea nitrogen, and male sex (all P<0.0001). Important additional predictors for the mortality risk model were higher serum urea nitrogen, male sex, and lower body mass index (all P<0.0001). CONCLUSIONS: Risk models using simple, readily obtainable clinical characteristics can provide important prognostic information in ambulatory patients with chronic heart failure with systolic dysfunction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Authors
O'Connor, CM; Whellan, DJ; Wojdyla, D; Leifer, E; Clare, RM; Ellis, SJ; Fine, LJ; Fleg, JL; Zannad, F; Keteyian, SJ; Kitzman, DW; Kraus, WE; Rendall, D; Piña, IL; Cooper, LS; Fiuzat, M; Lee, KL
MLA Citation
O'Connor, CM, Whellan, DJ, Wojdyla, D, Leifer, E, Clare, RM, Ellis, SJ, Fine, LJ, Fleg, JL, Zannad, F, Keteyian, SJ, Kitzman, DW, Kraus, WE, Rendall, D, Piña, IL, Cooper, LS, Fiuzat, M, and Lee, KL. "Factors related to morbidity and mortality in patients with chronic heart failure with systolic dysfunction: the HF-ACTION predictive risk score model." Circ Heart Fail 5.1 (January 2012): 63-71.
PMID
22114101
Source
pubmed
Published In
Circulation. Heart failure
Volume
5
Issue
1
Publish Date
2012
Start Page
63
End Page
71
DOI
10.1161/CIRCHEARTFAILURE.111.963462

Extant health behaviors and uptake of standardized vs tailored health messages among cancer survivors enrolled in the FRESH START trial: a comparison of fighting-spirits vs fatalists.

OBJECTIVE: Cancer coping styles have been associated with several cancer-related outcomes. We examined whether baseline lifestyle behaviors differed between cancer survivors with fatalistic vs fighting-spirit coping styles, and whether there was differential response to two diet-exercise mailed-print interventions, one standardized and another individually tailored. METHODS: Baseline differences by coping style are presented for 628 breast and prostate cancer survivors who participated in the FRESH START trial, along with multivariable analyses on rates of uptake by coping style and arm assignment for those completing the 2-year trial. RESULTS: At baseline, several differences were observed between fighting-spirits and fatalists, with the former significantly more likely to be white, younger, leaner, more-educated and at risk for depression, and less likely to consume 5+fruits and vegetables (F&V)/day (p-values<0.05). Improvements in physical activity were observed, with fighting-spirits exhibiting the greatest gains from baseline to Year-1, regardless of intervention type; but by Year-2, these differences diminished as fatalists gained ground. Moreover, fatalists who received standardized intervention material also charted steady improvements in F&V intake over the study period; by Year-2, 58.1% of fatalists achieved the 5-a-day goal vs 44.6% of fighting-spirits (p-value<0.05). CONCLUSIONS: Lifestyle behaviors and health message uptake differs by cancer coping style. Although tailored interventions appear most effective and minimize differential uptake, standardized interventions also can improve behaviors, though fighting-spirits may require additional boosters to maintain change.

Authors
Wilkinson, AV; Barrera, SL; McBride, CM; Snyder, DC; Sloane, R; Meneses, KM; Pekmezi, D; Kraus, WE; Demark-Wahnefried, W
MLA Citation
Wilkinson, AV, Barrera, SL, McBride, CM, Snyder, DC, Sloane, R, Meneses, KM, Pekmezi, D, Kraus, WE, and Demark-Wahnefried, W. "Extant health behaviors and uptake of standardized vs tailored health messages among cancer survivors enrolled in the FRESH START trial: a comparison of fighting-spirits vs fatalists." Psychooncology 21.1 (January 2012): 108-113.
PMID
21061408
Source
pubmed
Published In
Psycho-Oncology
Volume
21
Issue
1
Publish Date
2012
Start Page
108
End Page
113
DOI
10.1002/pon.1870

Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)). METHODS: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test. RESULTS: Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both). CONCLUSIONS: Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I). TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151.

Authors
Huffman, KM; Redman, LM; Landerman, LR; Pieper, CF; Stevens, RD; Muehlbauer, MJ; Wenner, BR; Bain, JR; Kraus, VB; Newgard, CB; Ravussin, E; Kraus, WE
MLA Citation
Huffman, KM, Redman, LM, Landerman, LR, Pieper, CF, Stevens, RD, Muehlbauer, MJ, Wenner, BR, Bain, JR, Kraus, VB, Newgard, CB, Ravussin, E, and Kraus, WE. "Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial." PLoS One 7.4 (2012): e28190-.
Website
http://hdl.handle.net/10161/10872
PMID
22523532
Source
pubmed
Published In
PloS one
Volume
7
Issue
4
Publish Date
2012
Start Page
e28190
DOI
10.1371/journal.pone.0028190

Conference Scene: Is personalized medicine ready for prime time?

This article provides a meeting report from the Duke Center for Personalized Medicine 2012 Symposium, which took place in Durham, NC, USA, on 29 March 2012. The event titled 'At the Interface of Clinical Research and Clinical Medicine, focused on many of the issues that arise as personalized medicine becomes integrated into clinical care. In particular, we summarize presentations on various topics: the future of genomic medicine, opportunities in pharmacogenomics and genetic testing; challenges in the clinical implementation of personalized medicine; systems medicine and biomedical informatics; the policy and education strategies for adopting personalized medicine; the common bond between comparative effectiveness and personalized medicine; and the value of personalized medicine. © 2012 Future Medicine Ltd.

Authors
Kraus, WE; Haga, SB; McLeod, HL; Staples, J; Ginsburg, GS
MLA Citation
Kraus, WE, Haga, SB, McLeod, HL, Staples, J, and Ginsburg, GS. "Conference Scene: Is personalized medicine ready for prime time?." Personalized Medicine 9.5 (2012): 475-478.
Source
scival
Published In
Personalized medicine
Volume
9
Issue
5
Publish Date
2012
Start Page
475
End Page
478
DOI
10.2217/pme.12.57

Osteoarthritis and the metabolic syndrome: More evidence that the etiology of OA is different in men and women

Authors
Huffman, KM; Kraus, WE
MLA Citation
Huffman, KM, and Kraus, WE. "Osteoarthritis and the metabolic syndrome: More evidence that the etiology of OA is different in men and women." Osteoarthritis and Cartilage 20.7 (2012): 603-604.
PMID
22521952
Source
scival
Published In
Osteoarthritis and Cartilage
Volume
20
Issue
7
Publish Date
2012
Start Page
603
End Page
604
DOI
10.1016/j.joca.2012.04.007

Critical appraisal of four IL-6 immunoassays.

BACKGROUND: Interleukin-6 (IL-6) contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs), with expected rises in IL-6 concentrations, were used to test the face validity of the various assays. METHODS AND FINDINGS: IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass) at time zero, a single infusion of insulin (0.025 U/kg body mass) at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD), an Invitrogen Luminex bead-based multiplex panel (LX), an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX), and R&D High Sensitivity ELISA (R&D). IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001) but only ULX correlated (r = 0.31, p = 0.0027) with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL) increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049), and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048). CONCLUSION: This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1-2 hours) and a late insulin-dependent response (detectable after 2 hours).

Authors
Thompson, DK; Huffman, KM; Kraus, WE; Kraus, VB
MLA Citation
Thompson, DK, Huffman, KM, Kraus, WE, and Kraus, VB. "Critical appraisal of four IL-6 immunoassays." PLoS One 7.2 (2012): e30659-.
Website
http://hdl.handle.net/10161/10874
PMID
22347395
Source
pubmed
Published In
PloS one
Volume
7
Issue
2
Publish Date
2012
Start Page
e30659
DOI
10.1371/journal.pone.0030659

A whole blood gene expression-based signature for smoking status

Background: Smoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status. Methods. Microarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite. Results: Microarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53). Conclusion: We have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression. © 2012 Beineke et al.; licensee BioMed Central Ltd.

Authors
Beineke, P; Fitch, K; Tao, H; Elashoff, MR; Rosenberg, S; Kraus, WE; Wingrove, JA
MLA Citation
Beineke, P, Fitch, K, Tao, H, Elashoff, MR, Rosenberg, S, Kraus, WE, and Wingrove, JA. "A whole blood gene expression-based signature for smoking status." BMC Medical Genomics 5 (2012).
PMID
23210427
Source
scival
Published In
BMC Medical Genomics
Volume
5
Publish Date
2012
DOI
10.1186/1755-8794-5-58

Statins, exercise, and skeletal muscle

Authors
Kraus, WE; Patel, MJ
MLA Citation
Kraus, WE, and Patel, MJ. "Statins, exercise, and skeletal muscle." Exercise and Sport Sciences Reviews 40.4 (2012): 187--.
PMID
23000956
Source
scival
Published In
Exercise and Sport Sciences Reviews
Volume
40
Issue
4
Publish Date
2012
Start Page
187-
DOI
10.1097/JES.0b013e31826f5640

Population approaches to improve diet, physical activity, and smoking habits: A scientific statement from the American heart association

Backround-: Poor lifestyle behaviors, including suboptimal diet, physical inactivity, and tobacco use, are leading causes of preventable diseases globally. Although even modest population shifts in risk substantially alter health outcomes, the optimal population-level approaches to improve lifestyle are not well established. Methods and Results-: For this American Heart Association scientific statement, the writing group systematically reviewed and graded the current scientific evidence for effective population approaches to improve dietary habits, increase physical activity, and reduce tobacco use. Strategies were considered in 6 broad domains: (1) Media and educational campaigns; (2) labeling and consumer information; (3) taxation, subsidies, and other economic incentives; (4) school and workplace approaches; (5) local environmental changes; and (6) direct restrictions and mandates. The writing group also reviewed the potential contributions of healthcare systems and surveillance systems to behavior change efforts. Several specific population interventions that achieved a Class I or IIa recommendation with grade A or B evidence were identified, providing a set of specific evidence-based strategies that deserve close attention and prioritization for wider implementation. Effective interventions included specific approaches in all 6 domains evaluated for improving diet, increasing activity, and reducing tobacco use. The writing group also identified several specific interventions in each of these domains for which current evidence was less robust, as well as other inconsistencies and evidence gaps, informing the need for further rigorous and interdisciplinary approaches to evaluate population programs and policies. CONCLUSIONS-: This systematic review identified and graded the evidence for a range of population-based strategies to promote lifestyle change. The findings provide a framework for policy makers, advocacy groups, researchers, clinicians, communities, and other stakeholders to understand and implement the most effective approaches. New strategic initiatives and partnerships are needed to translate this evidence into action. © 2012 American Heart Association, Inc.

Authors
Mozaffarian, D; Afshin, A; Benowitz, NL; Bittner, V; Daniels, SR; Franch, HA; Jacobs, DR; Kraus, WE; Kris-Etherton, PM; Krummel, DA; Popkin, BM; Whitsel, LP; Zakai, NA
MLA Citation
Mozaffarian, D, Afshin, A, Benowitz, NL, Bittner, V, Daniels, SR, Franch, HA, Jacobs, DR, Kraus, WE, Kris-Etherton, PM, Krummel, DA, Popkin, BM, Whitsel, LP, and Zakai, NA. "Population approaches to improve diet, physical activity, and smoking habits: A scientific statement from the American heart association." Circulation 126.12 (2012): 1514-1563.
PMID
22907934
Source
scival
Published In
Circulation
Volume
126
Issue
12
Publish Date
2012
Start Page
1514
End Page
1563
DOI
10.1161/CIR.0b013e318260a20b

A gender-specific blood-based gene expression score for assessing obstructive coronary artery disease in nondiabetic patients: Results of the Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) Trial

Background: Currently available noninvasive tests to risk stratify patients for obstructive coronary disease result in many unnecessary cardiac catheterizations, especially in women. We sought to compare the diagnostic accuracy of presenting symptoms, noninvasive test results, and a gene expression score (GES) in identifying obstructive coronary artery disease (CAD) according to gender, using quantitative coronary angiography as the criterion standard. Methods: The PREDICT trial is a prospective multicenter observational study designed to develop and validate gene expression algorithms to assess obstructive CAD, defined as at least one ≥ 50% diameter stenosis measured by quantitative coronary angiography. Patients referred for diagnostic cardiac catheterization with suspected but previously unknown CAD were enrolled. Noninvasive myocardial perfusion imaging (MPI) was available in 60% of patients. The GES, comprising gender-specific age functions and 6 gene expression terms containing 23 genes, was performed for all patients. Results: A total of 1,160 consecutive patients (57.6% men and 42.4% women) were enrolled in PREDICT. The prevalence of obstructive CAD was 46.7% in men and 22.0% in women. Chest pain symptoms were a discriminator of obstructive CAD in men (P <.001) but not in women. The positive predictive value of MPI was significantly higher in men (45%) than in women (22%). An abnormal site-read MPI was not significantly associated with obstructive or severity of CAD. The GES was significantly associated with a 2-fold increase in the odds of obstructive CAD for every 10-point increment in the GES and had a significant association with all measures of severity and burden of CAD. By multivariable analysis, GES was an independent predictor of obstructive CAD in the overall population (odds ratio [OR] 2.53, P =.001) and in the male (OR 1.99, P =.001) and female (OR 3.45, P =.001) subgroups separately, whereas MPI was not. Conclusions: Commonly used diagnostic approaches including symptom evaluation and MPI performed less well in women than in men for identifying significant CAD. In contrast, gender-specific GES performed similarly in women and men. Gene expression score offers a reliable diagnostic approach for the assessment of nondiabetic patients and, in pticular, women with suspected obstructive CAD. © 2012 Mosby, Inc. All rights reserved.

Authors
Lansky, A; Elashoff, MR; Ng, V; McPherson, J; Lazar, D; Kraus, WE; Voros, S; Schwartz, RS; Topol, EJ
MLA Citation
Lansky, A, Elashoff, MR, Ng, V, McPherson, J, Lazar, D, Kraus, WE, Voros, S, Schwartz, RS, and Topol, EJ. "A gender-specific blood-based gene expression score for assessing obstructive coronary artery disease in nondiabetic patients: Results of the Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) Trial." American Heart Journal 164.3 (2012): 320-326.
PMID
22980297
Source
scival
Published In
American Heart Journal
Volume
164
Issue
3
Publish Date
2012
Start Page
320
End Page
326
DOI
10.1016/j.ahj.2012.05.012

Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: Results from Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training

Background: The prognostic ability of a single measurement of peak oxygen uptake (VO2) is well established in patients with chronic heart failure. The relation between a change in peak VO2 and clinical outcomes is not well defined. Methods and Results: This investigation determined whether an increase in peak VO2 was associated with a lower risk of the primary end point of time to all-cause mortality or all-cause hospitalization and 3 secondary end points. In Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training, an exercise training trial for patients with systolic heart failure, cardiopulmonary exercise tests were performed at baseline and ≈3 months later in 1620 participants. Median peak VO2 in the combined sample increased from 15.0 (11.9-18.0 Q1-Q3) to 15.4 (12.3-18.7 Q1-Q3) mL·kg-1·min-1. Every 6% increase in peak VO2, adjusted for other significant predictors, was associated with a 5% lower risk of the primary end point (hazard ratio=0.95; CI=0.93-0.98; P <0.001); a 4% lower risk of the secondary end point of time to cardiovascular mortality or cardiovascular hospitalization (hazard ratio=0.96; CI=0.94-0.99; P <0.001); an 8% lower risk of cardiovascular mortality or heart failure hospitalization (hazard ratio=0.92; CI=0.88-0.96; P <0.001); and a 7% lower all-cause mortality (hazard ratio=0.93; CI=0.90-0.97; P <0.001). Conclusions: Among patients with chronic systolic heart failure, a modest increase in peak VO2 over 3 months was associated with a more favorable outcome. Monitoring the change in peak VO2 for such patients may have benefit in assessing prognosis. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437. © 2012 American Heart Association, Inc.

Authors
Swank, AM; Horton, J; Fleg, JL; Fonarow, GC; Keteyian, S; Goldberg, L; Wolfel, G; Handberg, EM; Bensimhon, D; Illiou, M-C; Vest, M; Ewald, G; Blackburn, G; Leifer, E; Cooper, L; Kraus, WE
MLA Citation
Swank, AM, Horton, J, Fleg, JL, Fonarow, GC, Keteyian, S, Goldberg, L, Wolfel, G, Handberg, EM, Bensimhon, D, Illiou, M-C, Vest, M, Ewald, G, Blackburn, G, Leifer, E, Cooper, L, and Kraus, WE. "Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: Results from Heart Failure and a Controlled Trial to Investigate Outcomes of Exercise Training." Circulation: Heart Failure 5.5 (2012): 579-585.
PMID
22773109
Source
scival
Published In
Circulation: Heart Failure
Volume
5
Issue
5
Publish Date
2012
Start Page
579
End Page
585
DOI
10.1161/CIRCHEARTFAILURE.111.965186

Obesity, insulin resistance, and skeletal muscle nitric oxide synthase

The molecular mechanisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means ± SE: nonobese, body mass index ± 25.5 ± 0.3 kg/m2, n = 13; obese, body mass index = 36.6 ± 0.4 kg/m2, n=14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensitivity index (SI). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. SI was significantly lower in the obese compared with the nonobese group (∼43%; P < 0.05), yet skeletal muscle iNOS protein expression was not different between nonobese and obese groups. Skeletal muscle eNOS protein was significantly higher in the nonobese than the obese group, and skeletal muscle nNOS protein tended to be higher (P = 0.054) in the obese compared with the nonobese group. Alternative analysis based on SI (high and low tertile) indicated that the most insulin-resistant group did not have significantly more skeletal muscle iNOS protein than the most insulin-sensitive group. In conclusion, human insulin resistance does not appear to be associated with an elevation in skeletal muscle iNOS protein in middle-aged individuals under fasting conditions. © 2012 the American Physiological Society.

Authors
Kraus, RM; Houmard, JA; Kraus, WE; Tanner, CJ; Pierce, JR; Choi, MD; Hickner, RC
MLA Citation
Kraus, RM, Houmard, JA, Kraus, WE, Tanner, CJ, Pierce, JR, Choi, MD, and Hickner, RC. "Obesity, insulin resistance, and skeletal muscle nitric oxide synthase." Journal of Applied Physiology 113.5 (2012): 758-765.
PMID
22797309
Source
scival
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
113
Issue
5
Publish Date
2012
Start Page
758
End Page
765
DOI
10.1152/japplphysiol.01018.2011

Whole blood gene expression testing for coronary artery disease in nondiabetic patients: Major adverse cardiovascular events and interventions in the PREDICT trial

The majority of first-time angiography patients are without obstructive coronary artery disease (CAD). A blood gene expression score (GES) for obstructive CAD likelihood was validated in the PREDICT study, but its relation to major adverse cardiovascular events (MACE) and revascularization was not assessed. Patients (N01,160) were followed up for MACE and revascularization 1 year post-index angiography and GES, with 1,116 completing follow-up. The 30-day event rate was 23% and a further 2.2% at 12 months. The GES was associated with MACE/ revascularizations (p<0.001) and added to clinical risk scores. Patients with GES >15 trended towards increased >30 days MACE/revascularization likelihood (odds ratio02.59, 95% confidence interval00.89-9.14, p00.082). MACE incidence © Springer Science+Business Media, LLC 2012.

Authors
Rosenberg, S; Elashoff, MR; Lieu, HD; Brown, BO; Kraus, WE; Schwartz, RS; Voros, S; Ellis, SG; Waksman, R; McPherson, JA; Lansky, AJ; Topol, EJ
MLA Citation
Rosenberg, S, Elashoff, MR, Lieu, HD, Brown, BO, Kraus, WE, Schwartz, RS, Voros, S, Ellis, SG, Waksman, R, McPherson, JA, Lansky, AJ, and Topol, EJ. "Whole blood gene expression testing for coronary artery disease in nondiabetic patients: Major adverse cardiovascular events and interventions in the PREDICT trial." Journal of Cardiovascular Translational Research 5.3 (2012): 366-374.
PMID
22396313
Source
scival
Published In
Journal of Cardiovascular Translational Research
Volume
5
Issue
3
Publish Date
2012
Start Page
366
End Page
374
DOI
10.1007/s12265-012-9353-z

Adverse metabolic response to regular exercise: is it a rare or common occurrence?

BACKGROUND: Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. METHODOLOGY/PRINCIPAL FINDINGS: An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified. The technical error (TE) defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473) and Blacks (N = 250) from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326), from INFLAME (N = 70), and from STRRIDE (N = 303); and Whites from a University of Maryland cohort (N = 160) and from a University of Jyvaskyla study (N = 105), for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4%) had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors. CONCLUSIONS/SIGNIFICANCE: Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription.

Authors
Bouchard, C; Blair, SN; Church, TS; Earnest, CP; Hagberg, JM; Häkkinen, K; Jenkins, NT; Karavirta, L; Kraus, WE; Leon, AS; Rao, DC; Sarzynski, MA; Skinner, JS; Slentz, CA; Rankinen, T
MLA Citation
Bouchard, C, Blair, SN, Church, TS, Earnest, CP, Hagberg, JM, Häkkinen, K, Jenkins, NT, Karavirta, L, Kraus, WE, Leon, AS, Rao, DC, Sarzynski, MA, Skinner, JS, Slentz, CA, and Rankinen, T. "Adverse metabolic response to regular exercise: is it a rare or common occurrence?." PLoS One 7.5 (2012): e37887-.
PMID
22666405
Source
pubmed
Published In
PloS one
Volume
7
Issue
5
Publish Date
2012
Start Page
e37887
DOI
10.1371/journal.pone.0037887

A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex

Background-Recent genome-wide association studies (GWAS) have identified several novel loci that reproducibly associate with coronary artery disease (CAD) and/or myocardial infarction risk. However, known common CAD risk variants explain only 10% of the predicted genetic heritability of the disease, suggesting that important genetic signals remain to be discovered. Methods and Results-We performed a discovery meta-analysis of 5 GWAS involving 13 949 subjects (7123 cases, 6826 control subjects) imputed at approximately 5 million single nucleotide polymorphisms, using pilot 1000 Genomes-based haplotypes. Promising loci were followed up in an additional 5 studies with 11 032 subjects (5211 cases, 5821 control subjects). A novel CAD locus on chromosome 6p21.3 in the major histocompatibility complex (MHC) between HCG27 and HLA-C was identified and achieved genome-wide significance in the combined analysis (rs3869109; pdiscovery=3.3×10-7, preplication=5.3×10 -4 pcombined=1.12×10-9). A subanalysis combining discovery GWAS showed an attenuation of significance when stringent corrections for European population structure were used (P=4.1×10-10 versus 3.2×10-7), suggesting that the observed signal is partly confounded due to population stratification. This gene dense region plays an important role in inflammation, immunity, and self- cell recognition. To determine whether the underlying association was driven by MHC class I alleles, we statistically imputed common HLA alleles into the discovery subjects; however, no single common HLA type contributed significantly or fully explained the observed association. Conclusions-We have identified a novel locus in the MHC associated with CAD. MHC genes regulate inflammation and T-cell responses that contribute importantly to the initiation and propagation of atherosclerosis. Further laboratory studies will be required to understand the biological basis of this association and identify the causative allele(s). © 2012 American Heart Association, Inc.

Authors
Davies, RW; Wells, GA; Stewart, AFR; Erdmann, J; Shah, SH; Ferguson, JF; Hall, AS; Anand, SS; Burnett, MS; Epstein, SE; Dandona, S; Chen, L; Nahrstaedt, J; Loley, C; König, IR; Kraus, WE; Granger, CB; Engert, JC; Hengstenberg, C; Wichmann, H-E; Schreiber, S; Tang, WHW; Ellis, SG; Rader, DJ; Hazen, SL; Reilly, MP; Samani, NJ; Schunkert, H; Roberts, R; McPherson, R
MLA Citation
Davies, RW, Wells, GA, Stewart, AFR, Erdmann, J, Shah, SH, Ferguson, JF, Hall, AS, Anand, SS, Burnett, MS, Epstein, SE, Dandona, S, Chen, L, Nahrstaedt, J, Loley, C, König, IR, Kraus, WE, Granger, CB, Engert, JC, Hengstenberg, C, Wichmann, H-E, Schreiber, S, Tang, WHW, Ellis, SG, Rader, DJ, Hazen, SL, Reilly, MP, Samani, NJ, Schunkert, H, Roberts, R, and McPherson, R. "A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex." Circulation: Cardiovascular Genetics 5.2 (2012): 217-225.
PMID
22319020
Source
scival
Published In
Circulation: Cardiovascular Genetics
Volume
5
Issue
2
Publish Date
2012
Start Page
217
End Page
225
DOI
10.1161/CIRCGENETICS.111.961243

Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: The multicenter CALERIE study

Calorie restriction (CR) is a component of most weight loss interventions and a potential strategy to slow aging. Accurate determination of energy intake and %CR is critical when interpreting the results of CR interventions; this is most accurately achieved using the doubly labeled water method to quantify total energy expenditure (TEE). However, the costs and analytical requirements of this method preclude its repeated use in many clinical trials. Our aims were to determine 1) the optimal TEE assessment time points for quantifying average energy intake and %CR during long-term CR interventions and 2) the optimal approach for quantifying short-term changes in body energy stores to determine energy intake and %CR during 2-wk DLW periods. Adults randomized to a CR intervention in the multicenter CALERIE study underwent measurements of TEE by doubly labeled water and body composition at baseline and months 1, 3, and 6. Average %CR achieved during the intervention was 24.9 ± 8.7%, which was computed using an approach that included four TEE assessment time points (i.e., TEE baseline, months 1, 3, and 6) plus the 6-mo change in body composition. Approaches that included fewer TEE assessments yielded %CR values of 23.4 ± 9.0 (TEE baseline, months 3 and 6), 25.0 ± 8.7 (TEE baseline, months 1 and 6), and 20.9 ± 7.1% (TEE baseline, month 6); the latter approach differed significantly from approach 1 (P < 0.001). TEE declined 9.6 ± 9.9% within 2-4 wk of CR beginning and then stabilized. Regression of daily home weights provided the most reliable estimate of short-term change in energy stores. In summary, optimal quantification of energy intake and %CR during weight loss necessitates a TEE measurement within the first month of CR to capture the rapid reduction in TEE. © 2012 the American Physiological Society.

Authors
Racette, SB; Das, SK; Bhapkar, M; Hadley, EC; Roberts, SB; Ravussin, E; Pieper, C; DeLany, JP; Kraus, WE; Rochon, J; Redman, LM
MLA Citation
Racette, SB, Das, SK, Bhapkar, M, Hadley, EC, Roberts, SB, Ravussin, E, Pieper, C, DeLany, JP, Kraus, WE, Rochon, J, and Redman, LM. "Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: The multicenter CALERIE study." American Journal of Physiology - Endocrinology and Metabolism 302.4 (2012): E441-E448.
PMID
22127229
Source
scival
Published In
American journal of physiology. Endocrinology and metabolism
Volume
302
Issue
4
Publish Date
2012
Start Page
E441
End Page
E448
DOI
10.1152/ajpendo.00290.2011

Why do individuals not lose more weight from an exercise intervention at a defined dose? an energy balance analysis

Weight loss resulting from an exercise intervention tends to be lower than predicted. Modest weight loss can arise from an increase in energy intake, physiological reductions in resting energy expenditure, an increase in lean tissue or a decrease in non-exercise activity. Lower than expected, weight loss could also arise from weak and invalidated assumptions within predictive models. To investigate these causes, we systematically reviewed studies that monitored compliance to exercise prescriptions and measured exercise-induced change in body composition. Changed body energy stores were calculated to determine the deficit between total daily energy intake and energy expenditures. This information combined with available measurements was used to critically evaluate explanations for low exercise-induced weight loss. We conclude that the small magnitude of weight loss observed from the majority of evaluated exercise interventions is primarily due to low doses of prescribed exercise energy expenditures compounded by a concomitant increase in caloric intake. © 2012 International Association for the Study of Obesity.

Authors
Thomas, DM; Bouchard, C; Church, T; Slentz, C; Kraus, WE; Redman, LM; Martin, CK; Silva, AM; Vossen, M; Westerterp, K; Heymsfield, SB
MLA Citation
Thomas, DM, Bouchard, C, Church, T, Slentz, C, Kraus, WE, Redman, LM, Martin, CK, Silva, AM, Vossen, M, Westerterp, K, and Heymsfield, SB. "Why do individuals not lose more weight from an exercise intervention at a defined dose? an energy balance analysis." Obesity Reviews 13.10 (2012): 835-847.
PMID
22681398
Source
scival
Published In
Obesity Reviews
Volume
13
Issue
10
Publish Date
2012
Start Page
835
End Page
847
DOI
10.1111/j.1467-789X.2012.01012.x

Relations of a marker of endothelial activation (s-VCAM) to function and mortality in community-dwelling older adults.

BACKGROUND: We wished to determine if a marker of endothelial dysfunction/activation soluble vascular cell adhesion molecule (s-VCAM)-was related to functional status and mortality in community-dwelling older adults independent of the known effects of markers of inflammation and coagulation. METHODS: Data came from the third and fourth in-person waves of the Duke Established Populations for Epidemiologic Studies of the Elderly. Participants (aged ≥ 71 years) had participated in a blood draw (N = 1,551) from which concentrations of s-VCAM, interleukin-6, and D-dimer were determined. Information was gathered in-person on demographics, health behaviors, chronic health conditions, and functional status (Katz, Rosow-Breslau, Nagi). Death was determined through the National Death Index. Multivariable regression analysis was used to examine the adjusted association of s-VCAM with functional status; Cox proportional hazards models ascertained hazard of mortality. RESULTS: Controlled analyses indicated that cross-sectionally, but not longitudinally (4 years later), greater s-VCAM concentrations were associated with poorer function as measured by the Katz and Rosow-Breslau scales (p < .05 for both), independent of interleukin-6 and D-dimer. In controlled analyses, s-VCAM (p = .002), D-dimer (p = .008), and interleukin-6 (p = .01) were independently related to 4-year mortality; 1 SD increase in log concentration conferred 1.2-, 1.1-, and 1.2-fold increases in mortality, respectively. The greatest hazard of mortality was observed within the first year after measurement. s-VCAM concentrations were not predictive of 15-year mortality. CONCLUSIONS: Independent of inflammation and coagulation markers, endothelial dysfunction serves as a marker of, and potentially contributes causally to, poor function and death in community-dwelling older adults.

Authors
Huffman, KM; Pieper, CF; Kraus, VB; Kraus, WE; Fillenbaum, GG; Cohen, HJ
MLA Citation
Huffman, KM, Pieper, CF, Kraus, VB, Kraus, WE, Fillenbaum, GG, and Cohen, HJ. "Relations of a marker of endothelial activation (s-VCAM) to function and mortality in community-dwelling older adults." J Gerontol A Biol Sci Med Sci 66.12 (December 2011): 1369-1375.
PMID
21798862
Source
pubmed
Published In
Journals of Gerontology: Series A
Volume
66
Issue
12
Publish Date
2011
Start Page
1369
End Page
1375
DOI
10.1093/gerona/glr121

Effect of heparin administration on metabolomic profiles in samples obtained during cardiac catheterization.

BACKGROUND: Metabolic profiling holds promise for early detection of coronary artery disease and assessing risk for ischemic events. Heparin is frequently administered (1) to treat acute coronary syndromes; and (2) during routine cardiac catheterization procedures. Because it stimulates lipolysis, heparin is a potential confounder of metabolic profiling in these populations. METHODS AND RESULTS: Using mass spectrometry and conventional immunoassays, we evaluated how unfractionated heparin administration affected 69 peripheral blood metabolites (acylcarnitines, amino acids, nonesterified fatty acids and their oxidation byproducts, conventional lipids, glucose, and C-reactive protein) in samples obtained pre- and postcardiac catheterization from 19 patients who received heparin and 10 patients who did not. Using unpaired t tests, we compared the changes in mean metabolite levels before and after the procedure between the nonheparin and heparin groups. Clinical characteristics of the nonheparin and heparin groups, indication for cardiac catheterization, procedure performed, and other periprocedural variables were similar. The mean change between pre- and postprocedure β-hydroxybutyrate (5.43 versus 66.84 μmol/L; P=0.009), ketones (21.17 versus 98.49 μmol/L; P=0.009), nonesterified fatty acids (0.37 versus 1.20 mmol/L; P=0.017), and triglycerides (-9.33 versus -36.50 mg/dL; P=0.007) was significantly different between the nonheparin and heparin groups, respectively. There were no significant differences between groups in the other metabolites measured. CONCLUSIONS: Heparin administration during cardiac catheterization induced changes in peripheral blood metabolites that were consistent with known lipolytic effects of heparin and define a metabolite signature associated with heparin administration. These findings are important for accurate interpretation of future metabolic profiling studies in populations exposed to heparin.

Authors
Brunner, MP; Shah, SH; Craig, DM; Stevens, RD; Muehlbauer, MJ; Bain, JR; Newgard, CB; Kraus, WE; Granger, CB; Sketch, MH; Newby, LK
MLA Citation
Brunner, MP, Shah, SH, Craig, DM, Stevens, RD, Muehlbauer, MJ, Bain, JR, Newgard, CB, Kraus, WE, Granger, CB, Sketch, MH, and Newby, LK. "Effect of heparin administration on metabolomic profiles in samples obtained during cardiac catheterization." Circ Cardiovasc Genet 4.6 (December 2011): 695-700.
PMID
22010138
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
4
Issue
6
Publish Date
2011
Start Page
695
End Page
700
DOI
10.1161/CIRCGENETICS.111.960575

Exercise among breast and prostate cancer survivors--what are their barriers?

INTRODUCTION: Despite proven benefits of regular physical activity, estimates indicate that few cancer survivors meet physical activity guidelines. The purpose of this paper is to identify and compare exercise barriers among cancer survivors, both cross-sectionally and longitudinally as they undergo home-based behavioral interventions. METHODS: Data on a sample of 452 breast and prostate cancer survivors who completed the FRESH START trial were analyzed collectively, as well as separately by cancer type. RESULTS: More total barriers (3.5 vs. 2.4; p < 0.01) were reported among breast cancer survivors compared with prostate cancer survivors. Commonly reported baseline exercise barriers among both groups were "too busy" (breast, 52% and prostate, 45%) and "no willpower" (breast, 51% and prostate, 44%). At baseline, breast cancer survivors who reported "no willpower" also reported 18.7 fewer minutes of physical activity compared with those not reporting this barrier (p < 0.01). Among prostate cancer survivors, this difference was 39.5 min (p < 0.01). Change in barriers was not associated with change in minutes of physical activity from baseline to post-intervention in either cancer survivor group. CONCLUSIONS: This is the largest study evaluating barriers and physical activity over time among cancer survivors. There are similarities and differences that both need to be taken into consideration when promoting physical activity among subgroups of survivors. IMPLICATIONS FOR CANCER SURVIVORS: Knowledge concerning barriers associated with reported physical activity may be helpful in designing optimally targeted physical activity interventions among breast and prostate cancer survivors.

Authors
Ottenbacher, AJ; Day, RS; Taylor, WC; Sharma, SV; Sloane, R; Snyder, DC; Kraus, WE; Demark-Wahnefried, W
MLA Citation
Ottenbacher, AJ, Day, RS, Taylor, WC, Sharma, SV, Sloane, R, Snyder, DC, Kraus, WE, and Demark-Wahnefried, W. "Exercise among breast and prostate cancer survivors--what are their barriers?." J Cancer Surviv 5.4 (December 2011): 413-419.
PMID
21598023
Source
pubmed
Published In
Journal of Cancer Survivorship
Volume
5
Issue
4
Publish Date
2011
Start Page
413
End Page
419
DOI
10.1007/s11764-011-0184-8

Peripheral Metabolite Profiles Discriminate Coronary Artery Disease in a Sequential Cohort of Cardiac Catheterization Patients

Authors
Bhattacharya, S; Craig, D; Haynes, C; Granger, CB; Stevens, RD; Hauser, ER; Kraus, WE; Newgard, CB; Newby, LK; Shah, SH
MLA Citation
Bhattacharya, S, Craig, D, Haynes, C, Granger, CB, Stevens, RD, Hauser, ER, Kraus, WE, Newgard, CB, Newby, LK, and Shah, SH. "Peripheral Metabolite Profiles Discriminate Coronary Artery Disease in a Sequential Cohort of Cardiac Catheterization Patients." CIRCULATION 124.21 (November 22, 2011).
Source
wos-lite
Published In
Circulation
Volume
124
Issue
21
Publish Date
2011

Genome-Wide Association Identifies Genetic Variants Associated With Vein Graft Stenosis After Coronary Artery Bypass Grafting

Authors
Shah, AA; Craig, DM; Haynes, C; Sebek, JK; Grass, E; Abramson, K; Smith, PK; Hauser, ER; Gregory, SG; Kraus, WE; Shah, SH
MLA Citation
Shah, AA, Craig, DM, Haynes, C, Sebek, JK, Grass, E, Abramson, K, Smith, PK, Hauser, ER, Gregory, SG, Kraus, WE, and Shah, SH. "Genome-Wide Association Identifies Genetic Variants Associated With Vein Graft Stenosis After Coronary Artery Bypass Grafting." November 22, 2011.
Source
wos-lite
Published In
Circulation
Volume
124
Issue
21
Publish Date
2011

Validation of a Gene Expression Test Score Using Coronary Artery Calcium and CT-Angiography as Reference Standard for Plaque Burden and Stenosis Evaluation

Authors
Voros, S; Budoff, MJ; Elashoff, MR; Sehnert, AJ; Lieu, H; Wingrove, J; Johnson, A; Daniels, SE; Rosenberg, S; Schwartz, RS; Kraus, WE; Topol, EJ
MLA Citation
Voros, S, Budoff, MJ, Elashoff, MR, Sehnert, AJ, Lieu, H, Wingrove, J, Johnson, A, Daniels, SE, Rosenberg, S, Schwartz, RS, Kraus, WE, and Topol, EJ. "Validation of a Gene Expression Test Score Using Coronary Artery Calcium and CT-Angiography as Reference Standard for Plaque Burden and Stenosis Evaluation." CIRCULATION 124.21 (November 22, 2011).
Source
wos-lite
Published In
Circulation
Volume
124
Issue
21
Publish Date
2011

Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population.

BACKGROUND: Red cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal. METHODS: In 1,489 patients with CAD and 8.4-15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated. RESULTS: RDW predicted all-cause mortality in a step-wise manner (HR=1.37 per quintile; 95% CI=1.29, 1.46; p-trend<0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r=0.181; p<0.001). With full adjustment, RDW remained significant (p-trend<0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR=1.33 per quintile, CI=1.15, 1.55; p-trend<0.001), but hsCRP did not predict mortality among normal controls. CONCLUSIONS: RDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS.

Authors
Lappé, JM; Horne, BD; Shah, SH; May, HT; Muhlestein, JB; Lappé, DL; Kfoury, AG; Carlquist, JF; Budge, D; Alharethi, R; Bair, TL; Kraus, WE; Anderson, JL
MLA Citation
Lappé, JM, Horne, BD, Shah, SH, May, HT, Muhlestein, JB, Lappé, DL, Kfoury, AG, Carlquist, JF, Budge, D, Alharethi, R, Bair, TL, Kraus, WE, and Anderson, JL. "Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population." Clin Chim Acta 412.23-24 (November 20, 2011): 2094-2099.
PMID
21821014
Source
pubmed
Published In
Clinica Chimica Acta
Volume
412
Issue
23-24
Publish Date
2011
Start Page
2094
End Page
2099
DOI
10.1016/j.cca.2011.07.018

Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. The mechanism(s) by which exercise training improves functional capacity is not understood. This study tested the hypothesis that in PAD patients who undergo supervised exercise training, increases in capillary density (CD) in calf muscle take place before improvements in peak oxygen uptake (VO(2)).Thirty-five PAD patients were randomly assigned to 12 weeks of directly supervised or home-based exercise training. Peak VO(2) testing and gastrocnemius muscle biopsies were performed at baseline and after training. CD (endothelial cells/mm(2)) was measured using immunofluorescence staining. After 3 weeks of directly supervised training, patients had an increase in CD (216±66 versus 284±77, P<0.01) but no increase in peak VO(2). However, after 12 weeks, peak VO(2) increased (15.3±2.8 versus 16.8±3.8, P<0.01), whereas in muscle, CD remained increased over baseline, but there were no changes in markers of oxidative capacity. Within subjects, CD was related to peak VO(2) before and after directly supervised training.Changes in CD in ischemic muscle with training may modulate the response to training, and those changes precede the increase in VO(2).

Authors
Duscha, BD; Robbins, JL; Jones, WS; Kraus, WE; Lye, RJ; Sanders, JM; Allen, JD; Regensteiner, JG; Hiatt, WR; Annex, BH
MLA Citation
Duscha, BD, Robbins, JL, Jones, WS, Kraus, WE, Lye, RJ, Sanders, JM, Allen, JD, Regensteiner, JG, Hiatt, WR, and Annex, BH. "Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients." Arteriosclerosis, thrombosis, and vascular biology 31.11 (November 2011): 2742-2748.
PMID
21868709
Source
epmc
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
31
Issue
11
Publish Date
2011
Start Page
2742
End Page
2748
DOI
10.1161/atvbaha.111.230441

Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT.

While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18-70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130-190 mg/dl or HDL cholesterol ≤ 40 mg/dl for men or ≤ 45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set, 2) AT, which was equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O(2) uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in subcutaneous abdominal fat (P < 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater reduction in liver fat score (P < 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode.

Authors
Slentz, CA; Bateman, LA; Willis, LH; Shields, AT; Tanner, CJ; Piner, LW; Hawk, VH; Muehlbauer, MJ; Samsa, GP; Nelson, RC; Huffman, KM; Bales, CW; Houmard, JA; Kraus, WE
MLA Citation
Slentz, CA, Bateman, LA, Willis, LH, Shields, AT, Tanner, CJ, Piner, LW, Hawk, VH, Muehlbauer, MJ, Samsa, GP, Nelson, RC, Huffman, KM, Bales, CW, Houmard, JA, and Kraus, WE. "Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT." Am J Physiol Endocrinol Metab 301.5 (November 2011): E1033-E1039.
PMID
21846904
Source
pubmed
Published In
American journal of physiology. Endocrinology and metabolism
Volume
301
Issue
5
Publish Date
2011
Start Page
E1033
End Page
E1039
DOI
10.1152/ajpendo.00291.2011

Improving cardiac rehabilitation referral patterns using computerized physician order entry systems.

Authors
Patel, MJ; Bensimhon, DR; Pierson, L; Ndubuizu, K; Craig, KP; Cummings, A; Granger, B; Heinsimer, JA; Kraus, WE
MLA Citation
Patel, MJ, Bensimhon, DR, Pierson, L, Ndubuizu, K, Craig, KP, Cummings, A, Granger, B, Heinsimer, JA, and Kraus, WE. "Improving cardiac rehabilitation referral patterns using computerized physician order entry systems." Am J Med 124.10 (October 2011): 908-910.
PMID
21722868
Source
pubmed
Published In
American Journal of Medicine
Volume
124
Issue
10
Publish Date
2011
Start Page
908
End Page
910
DOI
10.1016/j.amjmed.2011.03.010

Metabolic deterioration of the sedentary control group in clinical trials.

Randomized clinical trials of exercise training regimens in sedentary individuals have provided a mechanistic understanding of the long-term health benefits and consequences of physical activity and inactivity. The sedentary control periods from these trials have provided evidence of the progressive metabolic deterioration that results from as little as 4-6 mo of continuing a physically inactive lifestyle. These clinical trials have also demonstrated that only a modest amount of physical activity is required to prevent this metabolic deterioration, and this amount of physical activity is consistent with current physical activity recommendations (150 min/wk of moderate intensity physical activity). These recommendations have been issued to the general population for a vast array of health benefits. While greater adherence to these recommendations should result in substantial improvements in the health of the population, these recommendations still remain inadequate for many individuals. An individual's physical activity requirements are influenced by such factors as an individual's diet, nonexercise physical activity patterns, genetic profile, and medications. Improving the understanding of how these factors influence an individual's physical activity requirements will help advance the field and help move the field toward the development of more personalized physical activity recommendations.

Authors
Patel, MJ; Slentz, CA; Kraus, WE
MLA Citation
Patel, MJ, Slentz, CA, and Kraus, WE. "Metabolic deterioration of the sedentary control group in clinical trials." J Appl Physiol (1985) 111.4 (October 2011): 1211-1217.
PMID
21778417
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
111
Issue
4
Publish Date
2011
Start Page
1211
End Page
1217
DOI
10.1152/japplphysiol.00421.2011

Serum Uric Acid Concentration and Physical Activity: the National Health and Nutrition Examination Survey 2003-2004

Authors
Ning, T; Pieper, C; Kraus, VB; Kraus, WE; Huffman, KM
MLA Citation
Ning, T, Pieper, C, Kraus, VB, Kraus, WE, and Huffman, KM. "Serum Uric Acid Concentration and Physical Activity: the National Health and Nutrition Examination Survey 2003-2004." October 2011.
Source
wos-lite
Published In
Arthritis and Rheumatism
Volume
63
Issue
10
Publish Date
2011
Start Page
S79
End Page
S79

Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT).

Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk factors; however, to our knowledge, no randomized clinical studies have addressed whether resistance training (RT) improves the MS when performed alone or combined with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years completed a 4-month inactive run-in period and were randomized to 1 of 3 eight-month exercise programs (n = 196). The exercise programs were (1) RT (3 days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting all major muscle groups); (2) AT (∼120 minutes/week at 75% of the maximum oxygen uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86 participants with complete data for all 5 MS criteria were used in the present analysis, and a continuous MS z score was calculated. Eight months of RT did not change the MS score. AT improved the MS score (p <0.07) and showed a trend toward significance compared to RT (p <0.10). AT/RT significantly decreased the MS score and was significantly different from RT alone. In conclusion, RT was not effective at improving the MS score; however, AT was effective. Combined AT and RT was similarly effective but not different from AT alone. When weighing the time commitment versus health benefit, the data suggest that AT alone was the most efficient mode of exercise for improving cardiometabolic health.

Authors
Bateman, LA; Slentz, CA; Willis, LH; Shields, AT; Piner, LW; Bales, CW; Houmard, JA; Kraus, WE
MLA Citation
Bateman, LA, Slentz, CA, Willis, LH, Shields, AT, Piner, LW, Bales, CW, Houmard, JA, and Kraus, WE. "Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT)." Am J Cardiol 108.6 (September 15, 2011): 838-844.
PMID
21741606
Source
pubmed
Published In
American Journal of Cardiology
Volume
108
Issue
6
Publish Date
2011
Start Page
838
End Page
844
DOI
10.1016/j.amjcard.2011.04.037

Control arms in exercise training studies: transitioning from an era of intervention efficacy to one of comparative clinical effectiveness research.

Authors
Huffman, KM; Slentz, CA; Kraus, WE
MLA Citation
Huffman, KM, Slentz, CA, and Kraus, WE. "Control arms in exercise training studies: transitioning from an era of intervention efficacy to one of comparative clinical effectiveness research." J Appl Physiol (1985) 111.3 (September 2011): 946-948.
PMID
21512150
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
111
Issue
3
Publish Date
2011
Start Page
946
End Page
948
DOI
10.1152/japplphysiol.00323.2011

Effects of an 8-month exercise training program on off-exercise physical activity.

PURPOSE: An active lifestyle is widely recognized as having a beneficial effect on cardiovascular health. However, no clear consensus exists as to whether exercise training increases overall physical activity energy expenditure (PAEE) or whether individuals participating in regular exercise compensate by reducing their off-exercise physical activity. The purpose of this study was to evaluate changes in PAEE in response to aerobic training (AT), resistance training (RT), or combined aerobic and resistance training (AT/RT). METHODS: Data are from 82 participants in the Studies of Targeted Risk Reduction Interventions through Defined Exercise-Aerobic Training versus Resistance Training study, a randomized trial of overweight (body mass index = 25-35 kg·m(-2)) adults, in which participants were randomized to receive 8 months of AT, RT, or AT/RT. All subjects completed a 4-month control period before randomization. PAEE was measured using triaxial RT3 accelerometers, which subjects wore for a 5- to 7-d period before and after the exercise intervention. Data reduction was performed with a previously published computer-based algorithm. RESULTS: There was no significant change in off-exercise PAEE in any of the exercise training groups. We observed a significant increase in total PAEE that included the exercise training, in both AT and AT/RT but not in RT. CONCLUSIONS: Eight months of exercise training was not associated with a compensatory reduction in off-exercise physical activity, regardless of exercise modality. The absence of compensation is particularly notable for AT/RT subjects, who performed a larger volume of exercise than did AT or RT subjects. We believe that the extended duration of our exercise training program was the key factor in allowing subjects to reach a new steady-state level of physical activity within their daily lives.

Authors
Rangan, VV; Willis, LH; Slentz, CA; Bateman, LA; Shields, AT; Houmard, JA; Kraus, WE
MLA Citation
Rangan, VV, Willis, LH, Slentz, CA, Bateman, LA, Shields, AT, Houmard, JA, and Kraus, WE. "Effects of an 8-month exercise training program on off-exercise physical activity." Med Sci Sports Exerc 43.9 (September 2011): 1744-1751.
PMID
21364488
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
43
Issue
9
Publish Date
2011
Start Page
1744
End Page
1751
DOI
10.1249/MSS.0b013e3182148a7e

Effect of peripheral arterial disease on functional and clinical outcomes in patients with heart failure (from HF-ACTION).

Patients with peripheral arterial disease (PAD) have lower functional capacity and worse clinical outcomes than age- and gender-matched patients. Few data exist on the relation of PAD to functional and clinical outcomes in patients with heart failure (HF). We sought to compare patients with HF with and without PAD for baseline functional capacity, response to exercise training, and clinical outcomes. HF-ACTION was a randomized controlled trial comparing usual care to structured exercise training plus usual care in patients with HF and an ejection fraction ≤35% and New York Heart Association class II to IV HF symptoms. Cardiopulmonary exercise testing occurred at enrollment, 3 months, and 1 year. Clinical follow-up occurred up to 4 years. Of the 2,331 HF-ACTION patients, 157 (6.8%) had PAD. At baseline, patients with HF and PAD had a shorter exercise duration (8.0 vs 9.8 minutes, p <0.001), lower peak oxygen consumption (12.5 vs 14.6 ml/kg/min, p <0.001), and shorter 6-minute walking distance (306 vs 371 m, p <0.001) compared to patients with HF without PAD. At 3 months patients with HF and PAD had less improvement on cardiopulmonary exercise testing (exercise duration 0.5 vs 1.1 minutes, p = 0.002; mean change in peak oxygen consumption 0.1 vs 0.6 ml/kg/min, p = 0.04) compared to patients with HF without PAD. PAD was an independent predictor of all-cause death or hospitalization (hazard ratio 1.31, 95% confidence interval 1.06 to 1.62, p = 0.011). Patients with PAD and HF had deceased baseline exercise capacity and decreased response to exercise training. In conclusion, PAD is an independent predictor of all-cause death or hospitalization in patients with HF.

Authors
Jones, WS; Clare, R; Ellis, SJ; Mills, JS; Fischman, DL; Kraus, WE; Whellan, DJ; O'Connor, CM; Patel, MR
MLA Citation
Jones, WS, Clare, R, Ellis, SJ, Mills, JS, Fischman, DL, Kraus, WE, Whellan, DJ, O'Connor, CM, and Patel, MR. "Effect of peripheral arterial disease on functional and clinical outcomes in patients with heart failure (from HF-ACTION)." Am J Cardiol 108.3 (August 1, 2011): 380-384.
PMID
21565325
Source
pubmed
Published In
American Journal of Cardiology
Volume
108
Issue
3
Publish Date
2011
Start Page
380
End Page
384
DOI
10.1016/j.amjcard.2011.03.057

Resource Use and Medical Costs by Cause of Death in HF-ACTION

Authors
Li, Y; Whellan, DJ; Dunlap, ME; Kraus, WE; Samsa, G; Schulman, KA; Zile, M; Reed, SD
MLA Citation
Li, Y, Whellan, DJ, Dunlap, ME, Kraus, WE, Samsa, G, Schulman, KA, Zile, M, and Reed, SD. "Resource Use and Medical Costs by Cause of Death in HF-ACTION." JOURNAL OF CARDIAC FAILURE 17.8 (August 2011): S78-S78.
Source
wos-lite
Published In
Journal of Cardiac Failure
Volume
17
Issue
8
Publish Date
2011
Start Page
S78
End Page
S78

Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease.

The aim of this study was to determine if skeletal muscle capillary density is lower in patients with peripheral artery disease (PAD) and if capillary density relates to functional limitations. PAD patients with intermittent claudication (IC) have a decreased exercise tolerance due to exercise-induced muscle ischemia. Despite the apparent role diminished arterial flow has in this population, the degree of walking pain and functional limitation is not entirely explained by altered hemodynamics of the affected limbs. We hypothesized that skeletal muscle capillary density is lower in PAD and is related to the functional impairment observed in this population. Sixty-four patients with PAD and 56 controls underwent cardiopulmonary exercise testing and a gastrocnemius muscle biopsy. A subset of these patients (48 PAD and 47 controls) underwent peak hyperemic flow testing via plethysmography. Capillary density in PAD patients was lower compared with controls (P < 0.001). After adjustment for several baseline demographic imbalances the model relating capillary density to peak oxygen consumption (Vo(2)) remained significant (P < 0.001). In PAD subjects, capillary density correlated with peak Vo(2), peak walking time (PWT), and claudication onset time (COT). Peak hyperemic blood flow related to peak Vo(2) in both PAD and control subjects. PAD is associated with lower capillary density, and capillary density is related to the functional impairment as defined by a reduced peak Vo(2), PWT, and COT. These findings suggest that alterations in microcirculation may contribute to functional impairment capacity in PAD.

Authors
Robbins, JL; Jones, WS; Duscha, BD; Allen, JD; Kraus, WE; Regensteiner, JG; Hiatt, WR; Annex, BH
MLA Citation
Robbins, JL, Jones, WS, Duscha, BD, Allen, JD, Kraus, WE, Regensteiner, JG, Hiatt, WR, and Annex, BH. "Relationship between leg muscle capillary density and peak hyperemic blood flow with endurance capacity in peripheral artery disease." J Appl Physiol (1985) 111.1 (July 2011): 81-86.
PMID
21512146
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
111
Issue
1
Publish Date
2011
Start Page
81
End Page
86
DOI
10.1152/japplphysiol.00141.2011

Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system.

OBJECTIVE: Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism. RESEARCH DESIGN AND METHODS: Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action. RESULTS: Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even-chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling. CONCLUSIONS: The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis.

Authors
Kovalik, J-P; Slentz, D; Stevens, RD; Kraus, WE; Houmard, JA; Nicoll, JB; Lea-Currie, YR; Everingham, K; Kien, CL; Buehrer, BM; Muoio, DM
MLA Citation
Kovalik, J-P, Slentz, D, Stevens, RD, Kraus, WE, Houmard, JA, Nicoll, JB, Lea-Currie, YR, Everingham, K, Kien, CL, Buehrer, BM, and Muoio, DM. "Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system." Diabetes 60.7 (July 2011): 1882-1893.
PMID
21602515
Source
pubmed
Published In
Diabetes
Volume
60
Issue
7
Publish Date
2011
Start Page
1882
End Page
1893
DOI
10.2337/db10-0427

Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease.

Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n = 205) and the CATHGEN cardiovascular study (n = 1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n = 879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p = 2 × 10(-6) and 5 × 10(-6), respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD.

Authors
Minear, MA; Crosslin, DR; Sutton, BS; Connelly, JJ; Nelson, SC; Gadson-Watson, S; Wang, T; Seo, D; Vance, JM; Sketch, MH; Haynes, C; Goldschmidt-Clermont, PJ; Shah, SH; Kraus, WE; Hauser, ER; Gregory, SG
MLA Citation
Minear, MA, Crosslin, DR, Sutton, BS, Connelly, JJ, Nelson, SC, Gadson-Watson, S, Wang, T, Seo, D, Vance, JM, Sketch, MH, Haynes, C, Goldschmidt-Clermont, PJ, Shah, SH, Kraus, WE, Hauser, ER, and Gregory, SG. "Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease." Hum Genet 129.6 (June 2011): 641-654.
PMID
21298289
Source
pubmed
Published In
Human Genetics
Volume
129
Issue
6
Publish Date
2011
Start Page
641
End Page
654
DOI
10.1007/s00439-011-0959-z

Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease.

Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.

Authors
Kenjale, AA; Ham, KL; Stabler, T; Robbins, JL; Johnson, JL; Vanbruggen, M; Privette, G; Yim, E; Kraus, WE; Allen, JD
MLA Citation
Kenjale, AA, Ham, KL, Stabler, T, Robbins, JL, Johnson, JL, Vanbruggen, M, Privette, G, Yim, E, Kraus, WE, and Allen, JD. "Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease." J Appl Physiol (1985) 110.6 (June 2011): 1582-1591.
PMID
21454745
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
110
Issue
6
Publish Date
2011
Start Page
1582
End Page
1591
DOI
10.1152/japplphysiol.00071.2011

Relationship of technetium-99m tetrofosmin-gated rest single-photon emission computed tomography myocardial perfusion imaging to death and hospitalization in heart failure patients: results from the nuclear ancillary study of the HF-ACTION trial.

BACKGROUND: We hypothesized that the severity of resting perfusion abnormalities assessed by the summed rest score (SRS) would be associated with a higher rate of adverse outcomes in patients with heart failure (HF) and reduced left ventricular (LV) ejection fraction (EF). METHODS: A subset of 240 subjects from HF-ACTION underwent resting technetium-99m tetrofosmin-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Images were evaluated using a 17-segment model to derive the SRS and additional nuclear variables. RESULTS: After adjusting for prespecified covariates, SRS was significantly associated with the primary end point (hazard ratio 0.98, 95% confidence interval [CI] 0.97-1.00, P = .04), with a higher SRS corresponding to lower risk of an event. This association was not present in the unadjusted analysis. The relationship between SRS and the primary outcome was likely due to a higher event ratein patients with ischemic HF and a low SRS. The LV phase SD was not predictive of the primary outcome (hazard ratio 1.00, 95% confidence interval 0.99-1.01, P = .49). In a post hoc analysis, nuclear variables provided incremental prognostic information when added to clinical information (P = .006). CONCLUSIONS: Gated SPECT MPI provides important information in patients with HF and reduced LVEF. In the adjusted analysis, SRS has an unexpected relationship with the primary end point. Phase SD was not associated with the primary end point. Rest-gated SPECT MPI provides incrementally greater prognostic information than clinical information alone.

Authors
Atchley, AE; Iskandrian, AE; Bensimhon, D; Ellis, SJ; Kitzman, DW; Shaw, LK; Pagnanelli, RA; Whellan, DJ; Gardin, JM; Kao, A; Abdul-Nour, K; Ewald, G; Walsh, MN; Kraus, WE; O'Connor, CM; Borges-Neto, S; HF-ACTION Trial Nuclear Ancillary Study Investigators,
MLA Citation
Atchley, AE, Iskandrian, AE, Bensimhon, D, Ellis, SJ, Kitzman, DW, Shaw, LK, Pagnanelli, RA, Whellan, DJ, Gardin, JM, Kao, A, Abdul-Nour, K, Ewald, G, Walsh, MN, Kraus, WE, O'Connor, CM, Borges-Neto, S, and HF-ACTION Trial Nuclear Ancillary Study Investigators, . "Relationship of technetium-99m tetrofosmin-gated rest single-photon emission computed tomography myocardial perfusion imaging to death and hospitalization in heart failure patients: results from the nuclear ancillary study of the HF-ACTION trial." Am Heart J 161.6 (June 2011): 1038-1045.
PMID
21641348
Source
pubmed
Published In
American Heart Journal
Volume
161
Issue
6
Publish Date
2011
Start Page
1038
End Page
1045
DOI
10.1016/j.ahj.2011.02.007

Multiplex Profiling Demonstrates That Circulating Adipokines Are Related To Insulin Sensitivity But Not BMI

Authors
Pierce, JR; Kraus, RM; Houmard, JA; Kraus, WE; Tanner, CJ; Choi, MD; Hickner, RC
MLA Citation
Pierce, JR, Kraus, RM, Houmard, JA, Kraus, WE, Tanner, CJ, Choi, MD, and Hickner, RC. "Multiplex Profiling Demonstrates That Circulating Adipokines Are Related To Insulin Sensitivity But Not BMI." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 43.5 (May 2011): 482-482.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
43
Issue
5
Publish Date
2011
Start Page
482
End Page
482

Physical Activity Frequency, Independent Of Volume, Is Directly Associated With C-reactive Protein: Nhanes 2003-2006

Authors
Whitfield, GP; Kohl, HW; Kraus, WE
MLA Citation
Whitfield, GP, Kohl, HW, and Kraus, WE. "Physical Activity Frequency, Independent Of Volume, Is Directly Associated With C-reactive Protein: Nhanes 2003-2006." Medicine & Science in Sports & Exercise 43.Suppl 1 (May 2011): 721-722.
Source
crossref
Published In
Medicine and Science in Sports and Exercise
Volume
43
Issue
Suppl 1
Publish Date
2011
Start Page
721
End Page
722
DOI
10.1249/01.MSS.0000402003.46997.7c

Increased Plasma Nitrite Enhances Exercise Performance in PAD:-A Nitric Oxide Effect?

Authors
Kenjale, A; Ham, KL; Stabler, T; Robbins, JL; Johnson, JL; VanBruggen, M; Privette, G; Yim, E; Kraus, WE; Allen, JD
MLA Citation
Kenjale, A, Ham, KL, Stabler, T, Robbins, JL, Johnson, JL, VanBruggen, M, Privette, G, Yim, E, Kraus, WE, and Allen, JD. "Increased Plasma Nitrite Enhances Exercise Performance in PAD:-A Nitric Oxide Effect?." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 43.5 (May 2011): 118-118.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
43
Issue
5
Publish Date
2011
Start Page
118
End Page
118

The Effects of Aerobic Training on Markers of Systemic Inflammation in Extremely Obese Minority Teens

Authors
Many, GM; Hurtado, M-E; Park, J-J; Spurney, CF; Rhee, LQ; Nuñez, SB; Hagberg, JM; Uwaifo, GI; Kraus, WE; Houmard, JA; Damsker, JM; Tanner, CJ; Rakhmanina, N; Janicic, N; Hoffman, EP
MLA Citation
Many, GM, Hurtado, M-E, Park, J-J, Spurney, CF, Rhee, LQ, Nuñez, SB, Hagberg, JM, Uwaifo, GI, Kraus, WE, Houmard, JA, Damsker, JM, Tanner, CJ, Rakhmanina, N, Janicic, N, and Hoffman, EP. "The Effects of Aerobic Training on Markers of Systemic Inflammation in Extremely Obese Minority Teens." Medicine & Science in Sports & Exercise 43.Suppl 1 (May 2011): 683-684.
Source
crossref
Published In
Medicine and Science in Sports and Exercise
Volume
43
Issue
Suppl 1
Publish Date
2011
Start Page
683
End Page
684
DOI
10.1249/01.MSS.0000401894.22933.f2

Plasma acylcarnitines are associated with physical performance in elderly men.

BACKGROUND: Metabolic profiling might provide insight into the biologic underpinnings of disability in older adults. METHODS: A targeted mass spectrometry-based platform was used to identify and quantify 45 plasma acylcarnitines in 77 older men with a mean age of 79 years and average body mass index of 28.4 kg/m(2). To control for type I error inherent in a test of multiple analytes, principal components analysis was employed to reduce the acylcarnitines from 45 separate metabolites, into a single "acylcarnitine factor." We then tested for an association between this acylcarnitine factor and multiple indices of physical performance and self-reported function. RESULTS: The acylcarnitine factor accounted for 40% of the total variance in 45 acylcarnitines. Of the metabolites analyzed, those that contributed most to our one-factor solution were even-numbered medium and long-chain species with side chains containing 10-18 carbons (factor loadings ≥0.70). Odd-numbered chain species, in contrast, had factor loadings 0.50 or less. Acylcarnitine factor scores were inversely related to physical performance as measured by the Short Physical Performance Battery total score, two of its three component scores (gait and chair stands Short Physical Performance Battery), and usual and maximal gait speeds (ρ = -0.324, -0.348, -0.309, -0.241, and -0.254, respectively; p < .05). CONCLUSIONS: Higher acylcarnitine factor scores were associated with lower levels of objectively measured physical performance in this group of older, largely overweight men. Metabolic profiles of rodents exhibiting lipid-induced mitochondrial dysfunction show a similar phenotypic predominance of medium- and long-chain acylcarnitines.

Authors
Lum, H; Sloane, R; Huffman, KM; Kraus, VB; Thompson, DK; Kraus, WE; Bain, JR; Stevens, R; Pieper, CF; Taylor, GA; Newgard, CB; Cohen, HJ; Morey, MC
MLA Citation
Lum, H, Sloane, R, Huffman, KM, Kraus, VB, Thompson, DK, Kraus, WE, Bain, JR, Stevens, R, Pieper, CF, Taylor, GA, Newgard, CB, Cohen, HJ, and Morey, MC. "Plasma acylcarnitines are associated with physical performance in elderly men." J Gerontol A Biol Sci Med Sci 66.5 (May 2011): 548-553.
PMID
21367961
Source
pubmed
Published In
Journals of Gerontology: Series A
Volume
66
Issue
5
Publish Date
2011
Start Page
548
End Page
553
DOI
10.1093/gerona/glr006

EFFECT OF HEPARIN ADMINISTRATION ON METABOLOMIC PROFILES FROM SAMPLES OBTAINED DURING CARDIAC CATHETERIZATION

Authors
Brunner, MP; Shah, SH; Craig, DM; Bain, JR; Muehlbauer, MJ; Newgard, CB; Kraus, WE; Granger, CB; Sketch, MH; Newby, LK
MLA Citation
Brunner, MP, Shah, SH, Craig, DM, Bain, JR, Muehlbauer, MJ, Newgard, CB, Kraus, WE, Granger, CB, Sketch, MH, and Newby, LK. "EFFECT OF HEPARIN ADMINISTRATION ON METABOLOMIC PROFILES FROM SAMPLES OBTAINED DURING CARDIAC CATHETERIZATION." April 5, 2011.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
57
Issue
14
Publish Date
2011
Start Page
E1147
End Page
E1147

Development of adherence metrics for caloric restriction interventions.

BACKGROUND: objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are freeliving. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs) of expected weight loss can be created from mathematical modeling of weight change to a given level of CR, conditional on the individual's set of baseline characteristics. These normograms can then be used by counselors to help the participant adhere to their caloric target. PURPOSE: (1) To develop models of weight loss over a year of caloric restriction-given demographics, and well-defined measurements of body mass index, total daily energy expenditure (TDEE) and %CR. (2) To utilize these models to develop normograms, given the level of caloric restriction prescribed, and measures of these variables. METHODS: Seventy-seven individuals completing a 6-12-month caloric restriction intervention (CALERIE) at three sites (Pennington Biomedical Research Center, Tufts University, and Washington University) and had body weight and body composition measured frequently. Energy intake (and %CR) was estimated from TDEE (by doubly labeled water) and body composition (by DXA) at baseline and months 1, 3, 6, and 12. Bodyweight was modeled to determine the predictors and distribution of the expected trajectory of percent weight change over 12 months of CR. RESULTS: As expected, CR was related to change in body weight. Controlling for time-varying measures, initially simple models of the functional form indicated that the trajectory of percent weight change was predicted by a nonlinear function of age, TDEE, %CR, and sex. Using these estimates, normograms for the weight change were developed. Our model estimates that the mean weight loss (% change from baseline weight) for an individual adherent to a 25% CR regimen is -10.9 ± 6.3% for females and -13.9 + 6.4% for men after 12 months. LIMITATIONS: There are several limitations. Sample sizes are small (n = 77), and, by design, the protocols, including prescribed CR, for the interventions differed by site, and not all subjects completed a year of follow-up. In addition, the inclusion of subjects by age and initial BMI was constricted, so that these results may not generalize to other populations including older and obese subjects. CONCLUSIONS: The trajectory of percent weight change during CR interventions in the presence of well-measured covariates can be modeled using simple nonlinear functions, and is related level of CR, the percent change in TDEE, gender, and age. Displayed on a normogram, individually tailored trajectories can be used by counselors and participants to monitor weight loss and adherence to a CR regimen.

Authors
Pieper, C; Redman, L; Racette, S; Roberts, S; Bhapkar, M; Rochon, J; Martin, C; Kraus, W; Das, S; Williamson, D; Ravussin, E
MLA Citation
Pieper, C, Redman, L, Racette, S, Roberts, S, Bhapkar, M, Rochon, J, Martin, C, Kraus, W, Das, S, Williamson, D, and Ravussin, E. "Development of adherence metrics for caloric restriction interventions." Clin Trials 8.2 (April 2011): 155-164.
PMID
21385788
Source
pubmed
Published In
Clinical Trials
Volume
8
Issue
2
Publish Date
2011
Start Page
155
End Page
164
DOI
10.1177/1740774511398369

Circulating Myostatin Decreases with Aerobic Exercise Training in Pre-Diabetic but not Diabetic Human Subjects

Authors
Hittel, D; Atkins, K; Kraus, WE; Sigal, RJ
MLA Citation
Hittel, D, Atkins, K, Kraus, WE, and Sigal, RJ. "Circulating Myostatin Decreases with Aerobic Exercise Training in Pre-Diabetic but not Diabetic Human Subjects." April 2011.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
25
Publish Date
2011

A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry.

A 58 kb region on chromosome 9p21.3 has consistently shown strong association with coronary artery disease (CAD) in multiple genome-wide association studies in populations of European and East Asian ancestry. In this study, we sought to further characterize the role of genetic variants in 9p21.3 in African American individuals. Apparently healthy African American siblings (n = 548) of patients with documented CAD < 60 years of age were genotyped and followed for incident CAD for up to 17 years. Tests of association for 86 single-nucleotide polymorphisms (SNPs) across the 9p21.3 region in a generalized estimating equation logistic framework under an additive model adjusting for traditional risk factors, family, follow-up time and population stratification were performed. A single SNP within the CDKN2B gene met stringent criteria for statistical significance, including permutation-based evaluations. This variant, rs3217989, was common (minor allele (G) frequency 0.242), conveyed protection against CAD (odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.07 to 0.50, P = 0.0008) and was replicated in a combined analysis of two additional case/control studies of prevalent CAD/MI in African Americans (n = 990, P = 0.024, OR = 0.779, 95% CI: 0.626-0.968). This is the first report of a CAD association signal in a population of African ancestry with a common variant within the CDKN2B gene, independent from previous findings in European and East Asian ancestry populations. The findings demonstrate a significant protective effect against incident CAD in African American siblings of persons with premature CAD, with replication in a combination of two additional African American cohorts.

Authors
Kral, BG; Mathias, RA; Suktitipat, B; Ruczinski, I; Vaidya, D; Yanek, LR; Quyyumi, AA; Patel, RS; Zafari, AM; Vaccarino, V; Hauser, ER; Kraus, WE; Becker, LC; Becker, DM
MLA Citation
Kral, BG, Mathias, RA, Suktitipat, B, Ruczinski, I, Vaidya, D, Yanek, LR, Quyyumi, AA, Patel, RS, Zafari, AM, Vaccarino, V, Hauser, ER, Kraus, WE, Becker, LC, and Becker, DM. "A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry." J Hum Genet 56.3 (March 2011): 224-229.
PMID
21270820
Source
pubmed
Published In
Journal of human genetics
Volume
56
Issue
3
Publish Date
2011
Start Page
224
End Page
229
DOI
10.1038/jhg.2010.171

Effect of caloric restriction with and without exercise on metabolic intermediates in nonobese men and women.

OBJECTIVES: The objective of the study was to evaluate whether serum concentrations of metabolic intermediates are related to adiposity and insulin sensitivity (Si) in overweight healthy subjects and compare changes in metabolic intermediates with similar weight loss achieved by diet only or diet plus exercise. DESIGN: This was a randomized controlled trial. PARTICIPANTS AND INTERVENTION: The cross-sectional study included 46 (aged 36.8 ± 1.0 yr) overweight (body mass index 27.8 ± 0.7 kg/m(2)) subjects enrolled in a 6-month study of calorie restriction. To determine the effect of diet only or diet plus exercise on metabolic intermediates, 35 subjects were randomized to control (energy intake at 100% of energy requirements); CR (25% calorie restriction), or CR+EX: (12.5% CR plus 12.5% increase in energy expenditure by exercise). MAIN OUTCOME MEASURES: Serum concentrations of eight fatty acids, 15 amino acids, and 45 acylcarnitines (ACs) measured by targeted mass spectrometry. RESULTS: In overweight subjects, the concentrations of C2 AC and long-chain ACs were positively associated with percent fat (R(2) = 0.75, P = 0.0001) and Si (R(2) = 0.12, P = 0.05). The percent fat (R(2) = 0.77, P < 0.0001), abdominal visceral fat (R(2) = 0.64, P < 0.0001), and intrahepatic fat (R(2) = 0.30, P = 0.0002) were positively associated with fatty acid concentrations. There was a significant increase in an AC factor (comprised of C2 and several medium chain ACs) in the CR group (P = 0.01). CONCLUSION: In nonobese subjects, fasted serum ACs are associated with Si and fat mass. Despite similar weight loss, serum ACs increase with CR alone but not CR+EX. A greater improvement in Si with weight loss during CR+EX interventions may be related to improved coupling of β-oxidation and tricarboxylic acid cycle flux induced by exercise.

Authors
Redman, LM; Huffman, KM; Landerman, LR; Pieper, CF; Bain, JR; Muehlbauer, MJ; Stevens, RD; Wenner, BR; Kraus, VB; Newgard, CB; Kraus, WE; Ravussin, E
MLA Citation
Redman, LM, Huffman, KM, Landerman, LR, Pieper, CF, Bain, JR, Muehlbauer, MJ, Stevens, RD, Wenner, BR, Kraus, VB, Newgard, CB, Kraus, WE, and Ravussin, E. "Effect of caloric restriction with and without exercise on metabolic intermediates in nonobese men and women." J Clin Endocrinol Metab 96.2 (February 2011): E312-E321.
PMID
21123443
Source
pubmed
Published In
Journal of Clinical Endocrinology and Metabolism
Volume
96
Issue
2
Publish Date
2011
Start Page
E312
End Page
E321
DOI
10.1210/jc.2010-1971

Exercise-induced changes in metabolic intermediates, hormones, and inflammatory markers associated with improvements in insulin sensitivity.

OBJECTIVE: To understand relationships between exercise training-mediated improvements in insulin sensitivity (S(I)) and changes in circulating concentrations of metabolic intermediates, hormones, and inflammatory mediators. RESEARCH DESIGN AND METHODS: Targeted mass spectrometry and enzyme-linked immunosorbent assays were used to quantify metabolic intermediates, hormones, and inflammatory markers at baseline, after 6 months of exercise training, and 2 weeks after exercise training cessation (n = 53). A principal components analysis (PCA) strategy was used to relate changes in these intermediates to changes in S(I). RESULTS: PCA reduced the number of intermediates from 90 to 24 factors composed of biologically related components. With exercise training, improvements in S(I) were associated with reductions in by-products of fatty acid oxidation and increases in glycine and proline (P < 0.05, R² = 0.59); these relationships were retained 15 days after cessation of exercise training (P < 0.05, R² = 0.34). CONCLUSIONS: These observations support prior observations in animal models that exercise training promotes more efficient mitochondrial β-oxidation and challenges current hypotheses regarding exercise training and glycine metabolism.

Authors
Huffman, KM; Slentz, CA; Bateman, LA; Thompson, D; Muehlbauer, MJ; Bain, JR; Stevens, RD; Wenner, BR; Kraus, VB; Newgard, CB; Kraus, WE
MLA Citation
Huffman, KM, Slentz, CA, Bateman, LA, Thompson, D, Muehlbauer, MJ, Bain, JR, Stevens, RD, Wenner, BR, Kraus, VB, Newgard, CB, and Kraus, WE. "Exercise-induced changes in metabolic intermediates, hormones, and inflammatory markers associated with improvements in insulin sensitivity." Diabetes Care 34.1 (January 2011): 174-176.
Website
http://hdl.handle.net/10161/10882
PMID
20921216
Source
pubmed
Published In
Diabetes Care
Volume
34
Issue
1
Publish Date
2011
Start Page
174
End Page
176
DOI
10.2337/dc10-0709

Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy.

BACKGROUND: In a robust and consistent manner, sustained caloric restriction (CR) has been shown to retard the aging process in a variety of animal species. Nonhuman primate studies suggest that CR may have similar effects in longer-lived species. The CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy) research program is the first systematic investigation of CR in nonobese human beings. In the phase 2 study, it is hypothesized that 2 years of sustained CR, involving a 25% reduction of ad libitum energy intake, results in beneficial effects similar to those observed in animal studies. This article presents the design and implementation of this study. METHODS: The study is a multicenter, parallel-group, randomized controlled trial. A sample of 225 participants (22.0 ≤ body mass index [BMI] < 28.0 kg/m(2)) is being enrolled with 2:1 allocation to CR. RESULTS: An intensive dietary and behavioral intervention was developed to achieve 25% CR and sustain it over the 2 years. Adherence is monitored using a doubly labeled water technique. Primary outcomes are resting metabolic rate and core temperature, and are assessed at baseline and at 6-month intervals. Secondary outcomes address oxyradical formation, cardiovascular risk markers, insulin sensitivity and secretion, immune function, neuroendocrine function, quality of life and cognitive function. Biologic materials are stored in a central repository. CONCLUSIONS: An intricate protocol has been developed to conduct this study. Procedures have been implemented to safeguard the integrity of the data and the conclusions drawn. The results will provide insight into the detrimental changes associated with the human aging process and how CR mitigates these effects.

Authors
Rochon, J; Bales, CW; Ravussin, E; Redman, LM; Holloszy, JO; Racette, SB; Roberts, SB; Das, SK; Romashkan, S; Galan, KM; Hadley, EC; Kraus, WE; CALERIE Study Group,
MLA Citation
Rochon, J, Bales, CW, Ravussin, E, Redman, LM, Holloszy, JO, Racette, SB, Roberts, SB, Das, SK, Romashkan, S, Galan, KM, Hadley, EC, Kraus, WE, and CALERIE Study Group, . "Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy." J Gerontol A Biol Sci Med Sci 66.1 (January 2011): 97-108.
PMID
20923909
Source
pubmed
Published In
Journals of Gerontology: Series A
Volume
66
Issue
1
Publish Date
2011
Start Page
97
End Page
108
DOI
10.1093/gerona/glq168

Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients

Abstract. Background: Alterations in gene expression in peripheral blood cells have been shown to be sensitive to the presence and extent of coronary artery disease (CAD). A non-invasive blood test that could reliably assess obstructive CAD likelihood would have diagnostic utility. Results: Microarray analysis of RNA samples from a 195 patient Duke CATHGEN registry case:control cohort yielded 2,438 genes with significant CAD association (p < 0.05), and identified the clinical/demographic factors with the largest effects on gene expression as age, sex, and diabetic status. RT-PCR analysis of 88 CAD classifier genes confirmed that diabetic status was the largest clinical factor affecting CAD associated gene expression changes. A second microarray cohort analysis limited to non-diabetics from the multi-center PREDICT study (198 patients; 99 case: control pairs matched for age and sex) evaluated gene expression, clinical, and cell population predictors of CAD and yielded 5,935 CAD genes (p < 0.05) with an intersection of 655 genes with the CATHGEN results. Biological pathway (gene ontology and literature) and statistical analyses (hierarchical clustering and logistic regression) were used in combination to select 113 genes for RT-PCR analysis including CAD classifiers, cell-type specific markers, and normalization genes. RT-PCR analysis of these 113 genes in a PREDICT cohort of 640 non-diabetic subject samples was used for algorithm development. Gene expression correlations identified clusters of CAD classifier genes which were reduced to meta-genes using LASSO. The final classifier for assessment of obstructive CAD was derived by Ridge Regression and contained sex-specific age functions and 6 meta-gene terms, comprising 23 genes. This algorithm showed a cross-validated estimated AUC = 0.77 (95% CI 0.73-0.81) in ROC analysis. Conclusions: We have developed a whole blood classifier based on gene expression, age and sex for the assessment of obstructive CAD in non-diabetic patients from a combination of microarray and RT-PCR data derived from studies of patients clinically indicated for invasive angiography. Clinical trial registration information. PREDICT, Personalized Risk Evaluation and Diagnosis in the Coronary Tree, http://www.clinicaltrials.gov, NCT00500617. © 2011 Elashoff et al; licensee BioMed Central Ltd.

Authors
Elashoff, MR; Wingrove, JA; Beineke, P; Daniels, SE; Tingley, WG; Rosenberg, S; Voros, S; Kraus, WE; Ginsburg, GS; Schwartz, RS; Ellis, SG; Tahirkheli, N; Waksman, R; McPherson, J; Lansky, AJ; Topol, EJ
MLA Citation
Elashoff, MR, Wingrove, JA, Beineke, P, Daniels, SE, Tingley, WG, Rosenberg, S, Voros, S, Kraus, WE, Ginsburg, GS, Schwartz, RS, Ellis, SG, Tahirkheli, N, Waksman, R, McPherson, J, Lansky, AJ, and Topol, EJ. "Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients." BMC Medical Genomics 4 (2011).
Website
http://hdl.handle.net/10161/13547
PMID
21443790
Source
scival
Published In
BMC Medical Genomics
Volume
4
Publish Date
2011
DOI
10.1186/1755-8794-4-26

The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations

Genome-wide association studies (GWASs) have identified polymorphic loci associated with coronary artery disease (CAD) risk factors (i.e. serum lipids) in adult populations (42-69 y). We hypothesized that younger populations would show a greater relative genetic component due to fewer confounding variables. We examined the influence of 20 GWAS loci associated with serum lipids and insulin metabolism, in a university student cohort (n = 548; mean age = 24 y), and replicated statistically associated results in a second study cohort of primary school students (n = 810, mean age = 11.5 y). Nineteen loci showed no relationship with studied risk factors in young adults. However, the ancestral allele of the rs646776 (SORT1) locus was strongly associated with increased LDL (C) in young adults [TT: 97.6 ± 1.0 mg/dL (n = 345) versus CT/CC: 87.3 ± 1.0 mg/dL (n = 203); p = 3 × 10] and children [TT: 94.0 ± 1.3 mg/dL (n = 551) versus CT/CC: 84.7 ± 1.4 mg/dL (n = 259); p = 4 × 10]. This locus is responsible for 3.6% of population variance in young adults and 2.5% of population variance in children. The effect size of the SORT1 locus is considerably higher in young populations (2.5-4.1%) compared with older subjects (1%). Copyright © 2011 International Pediatric Research Foundation, Inc.

Authors
Devaney, JM; Thompson, PD; Visich, PS; Saltarelli, WA; Gordon, PM; Orkunoglu-Suer, EF; Gordish-Dressman, H; Harmon, BT; Bradbury, MK; Panchapakesan, K; Khianey, R; Hubal, MJ; Clarkson, PM; Pescatello, LS; Zoeller, RF; Moyna, NM; Angelopoulos, TJ; Kraus, WE; Hoffman, EP
MLA Citation
Devaney, JM, Thompson, PD, Visich, PS, Saltarelli, WA, Gordon, PM, Orkunoglu-Suer, EF, Gordish-Dressman, H, Harmon, BT, Bradbury, MK, Panchapakesan, K, Khianey, R, Hubal, MJ, Clarkson, PM, Pescatello, LS, Zoeller, RF, Moyna, NM, Angelopoulos, TJ, Kraus, WE, and Hoffman, EP. "The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations." Pediatric Research 69.6 (2011): 538-543.
PMID
21297524
Source
scival
Published In
Pediatric Research
Volume
69
Issue
6
Publish Date
2011
Start Page
538
End Page
543
DOI
10.1203/PDR.0b013e3182139227

Effect of calorie restriction on the free-living physical activity levels of nonobese humans: Results of three randomized trials

Effect of calorie restriction on the free-living physical activity levels of nonobese humans: Results of three randomized trials. J Appl Physiol 110: 956-963, 2011. First published February 3, 2011; doi:10.1152/japplphysiol.00846. 2009.- The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5-29.9 kg/m2) adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE - RMR - 0.1 = TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity. Copyright © 2011 the American Physiological Society.

Authors
Martin, CK; Das, SK; Lindblad, L; Racette, SB; McCrory, MA; Weiss, EP; DeLany, JP; Kraus, WE
MLA Citation
Martin, CK, Das, SK, Lindblad, L, Racette, SB, McCrory, MA, Weiss, EP, DeLany, JP, and Kraus, WE. "Effect of calorie restriction on the free-living physical activity levels of nonobese humans: Results of three randomized trials." Journal of Applied Physiology 110.4 (2011): 956-963.
PMID
21292847
Source
scival
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
110
Issue
4
Publish Date
2011
Start Page
956
End Page
963
DOI
10.1152/japplphysiol.00846.2009

Genomic predictors of the maximal O2 uptake response to standardized exercise training programs

Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, the heritability of gains in maximal O2 uptake (V̇O 2max) after exposure to a standardized 20-wk exercise program was estimated at 47%. A genomewide association study based on 324,611 single-nucleotide polymorphisms (SNPs) was undertaken to identify SNPs associated with improvements in V̇O2max Based on single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 × 10 -4. Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21 SNPs that accounted for 49% of the variance in V̇O 2max trainability. Subjects who carried ≤9 favorable alleles at these 21 SNPs improved theirV̇O2max by 221 ml/min, whereas those who carried ≥19 of these alleles gained, on average, 604 ml/min. The strongest association was with rs6552828, located in the acyl-CoA synthase long-chain member 1 (ACSL1) gene, which accounted by itself for ∼6% of the training response of V̇O2max. The genes nearest to the SNPs that were the strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1); glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K+ channel, voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated in 40-to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in Studies of a Targeted Risk Reduction Intervention Through Defined Exercise (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women exercise trained in the Dose Response to Exercise (DREW) study (n = 112): rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162 ∼68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains inV̇ O2max in HERITAGE whites were replicated in HERITAGE blacks (n = 247). These genomic predictors of the response ofV̇ O2max to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular exercise. Large-scale replication studies are warranted. © 2011 the American Physiological Society.

Authors
Bouchard, C; Sarzynski, MA; Rice, TK; Kraus, WE; Church, TS; Sung, YJ; Rao, DC; Rankinen, T
MLA Citation
Bouchard, C, Sarzynski, MA, Rice, TK, Kraus, WE, Church, TS, Sung, YJ, Rao, DC, and Rankinen, T. "Genomic predictors of the maximal O2 uptake response to standardized exercise training programs." Journal of Applied Physiology 110.5 (2011): 1160-1170.
PMID
21183627
Source
scival
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
110
Issue
5
Publish Date
2011
Start Page
1160
End Page
1170
DOI
10.1152/japplphysiol.00973.2010

Effects of an eight-month exercise training program on off-exercise physical activity

PURPOSE: An active lifestyle is widely recognized as having a beneficial effect on cardiovascular health. However, no clear consensus exists as to whether exercise training increases overall physical activity energy expenditure (PAEE) or whether individuals participating in regular exercise compensate by reducing their off exercise physical activity. The purpose of this study was to evaluate changes in PAEE in response to aerobic training (AT), resistance training (RT), or combined aerobic and resistance training (AT/RT). METHODS: Data are from 82 participants in the STRRIDE-AT/RT study, a randomized trial of overweight (BMI 25-35 kg/m) adults, in which participants were randomized to receive eight months of AT, RT, or AT/RT. All subjects completed a four-month control period prior to randomization. PAEE was measured using Triaxial RT3 accelerometers, which subjects wore for a five-to-seven day period before and after the exercise intervention. Data reduction was performed with a previously published computer based algorithm. RESULTS: There was no significant change in off-exercise PAEE in any of the exercise training groups. We observed a significant increase in total PAEE that included the exercise training, in both AT and AT/RT, but not in RT. CONCLUSIONS: Eight months of exercise training was not associated with a compensatory reduction in off-exercise physical activity, regardless of exercise modality. The absence of compensation is particularly notable for AT/RT subjects, who performed a larger volume of exercise than did AT or RT subjects. We believe that the extended duration of our exercise training program was the key factor in allowing subjects to reach a new steady state level of physical activity within their daily lives.

Authors
Rangan, VV; Willis, LH; Slentz, CA; Bateman, LA; Shields, AT; Houmard, JA; Kraus, WE
MLA Citation
Rangan, VV, Willis, LH, Slentz, CA, Bateman, LA, Shields, AT, Houmard, JA, and Kraus, WE. "Effects of an eight-month exercise training program on off-exercise physical activity." Medicine & Science in Sports & Exercise (2011).
Source
scival
Published In
Medicine and Science in Sports and Exercise
Publish Date
2011
DOI
10.1249/MSS.0b013e3182148a7e

AKT1 polymorphisms are associated with risk for metabolic syndrome

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40-65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations. © 2010 The Author(s).

Authors
Devaney, JM; Gordish-Dressman, H; Harmon, BT; Bradbury, MK; Devaney, SA; Harris, TB; Thompson, PD; Clarkson, PM; Price, TB; Angelopoulos, TJ; Gordon, PM; Moyna, NM; Pescatello, LS; Visich, PS; Zoeller, RF; Seip, RL; Seo, J; Kim, BH; Tosi, LL; Garcia, M; Li, R; Zmuda, JM; Delmonico, MJ; Lindsay, RS; Howard, BV; Kraus, WE; Hoffman, EP
MLA Citation
Devaney, JM, Gordish-Dressman, H, Harmon, BT, Bradbury, MK, Devaney, SA, Harris, TB, Thompson, PD, Clarkson, PM, Price, TB, Angelopoulos, TJ, Gordon, PM, Moyna, NM, Pescatello, LS, Visich, PS, Zoeller, RF, Seip, RL, Seo, J, Kim, BH, Tosi, LL, Garcia, M, Li, R, Zmuda, JM, Delmonico, MJ, Lindsay, RS, Howard, BV, Kraus, WE, and Hoffman, EP. "AKT1 polymorphisms are associated with risk for metabolic syndrome." Human Genetics 129.2 (2011): 129-139.
PMID
21061022
Source
scival
Published In
Human Genetics
Volume
129
Issue
2
Publish Date
2011
Start Page
129
End Page
139
DOI
10.1007/s00439-010-0910-8

Exercise in Heart Failure

Authors
Kraus, WE
MLA Citation
Kraus, WE. "Exercise in Heart Failure." Heart Failure (2011): 834-844.
Source
scival
Published In
Heart Failure
Publish Date
2011
Start Page
834
End Page
844
DOI
10.1016/B978-1-4160-5895-3.10057-9

Effect of microRNA modulation on bioartificial muscle function.

Cellular therapies have recently employed the use of small RNA molecules, particularly microRNAs (miRNAs), to regulate various cellular processes that may be altered in disease states. In this study, we examined the effect of transient muscle-specific miRNA inhibition on the function of three-dimensional skeletal muscle cultures, or bioartificial muscles (BAMs). Skeletal myoblast differentiation in vitro is enhanced by inhibiting a proliferation-promoting miRNA (miR-133) expressed in muscle tissues. As assessed by functional force measurements in response to electrical stimulation at frequencies ranging from 0 to 20 Hz, peak forces exhibited by BAMs with miR-133 inhibition (anti-miR-133) were on average 20% higher than the corresponding negative control, although dynamic responses to electrical stimulation in miRNA-transfected BAMs and negative controls were similar to nontransfected controls. Immunostaining for alpha-actinin and myosin also showed more distinct striations and myofiber organization in anti-miR-133 BAMs, and fiber diameters were significantly larger in these BAMs over both the nontransfected and negative controls. Compared to the negative control, anti-miR-133 BAMs exhibited more intense nuclear staining for Mef2, a key myogenic differentiation marker. To our knowledge, this study is the first to demonstrate that miRNA mediation has functional effects on tissue-engineered constructs.

Authors
Rhim, C; Cheng, CS; Kraus, WE; Truskey, GA
MLA Citation
Rhim, C, Cheng, CS, Kraus, WE, and Truskey, GA. "Effect of microRNA modulation on bioartificial muscle function." Tissue Eng Part A 16.12 (December 2010): 3589-3597.
Website
http://hdl.handle.net/10161/3365
PMID
20670163
Source
pubmed
Published In
Tissue Engineering, Part A
Volume
16
Issue
12
Publish Date
2010
Start Page
3589
End Page
3597
DOI
10.1089/ten.TEA.2009.0601

Identification of a Rare Variant Near Neurexin 1 Associated with Coronary Artery Disease

Authors
Stewart, AF; Dandona, S; Fan, M; Almontashiri, N; Chen, L; Davies, RW; Wells, GA; Tang, W; Hazen, SL; Ellix, S; Reilley, MP; Epstein, S; Rader, DJ; Engert, JC; Anand, S; Kathiresan, S; Cupples, AL; O'Donnell, CJ; Shah, S; Kraus, WE; Granger, CB; McPherson, R; Roberts, R
MLA Citation
Stewart, AF, Dandona, S, Fan, M, Almontashiri, N, Chen, L, Davies, RW, Wells, GA, Tang, W, Hazen, SL, Ellix, S, Reilley, MP, Epstein, S, Rader, DJ, Engert, JC, Anand, S, Kathiresan, S, Cupples, AL, O'Donnell, CJ, Shah, S, Kraus, WE, Granger, CB, McPherson, R, and Roberts, R. "Identification of a Rare Variant Near Neurexin 1 Associated with Coronary Artery Disease." CIRCULATION 122.21 (November 23, 2010).
Source
wos-lite
Published In
Circulation
Volume
122
Issue
21
Publish Date
2010

Peripheral Artery Disease is Associated with Worse Functional and Clinical Outcomes in Heart Failure Patients: HF-ACTION substudy

Authors
Jones, WS; Clare, R; Ellis, SJ; Mills, JS; Fischman, DL; Kraus, WE; Whellan, DJ; O'Connor, CM; Patel, MR
MLA Citation
Jones, WS, Clare, R, Ellis, SJ, Mills, JS, Fischman, DL, Kraus, WE, Whellan, DJ, O'Connor, CM, and Patel, MR. "Peripheral Artery Disease is Associated with Worse Functional and Clinical Outcomes in Heart Failure Patients: HF-ACTION substudy." CIRCULATION 122.21 (November 23, 2010).
Source
wos-lite
Published In
Circulation
Volume
122
Issue
21
Publish Date
2010

Red Cell Distribution Width and C-Reactive Protein in Predicting Mortality in Patients with Coronary Disease and in a Normal Comparison Population

Authors
Lappe, JM; Horne, BD; Shah, SH; May, HT; Muhlestein, JB; Lappe, DL; Kfoury, AG; Carlquist, JF; Budge, D; Alharethi, R; Bair, TL; Kraus, WE; Anderson, JL
MLA Citation
Lappe, JM, Horne, BD, Shah, SH, May, HT, Muhlestein, JB, Lappe, DL, Kfoury, AG, Carlquist, JF, Budge, D, Alharethi, R, Bair, TL, Kraus, WE, and Anderson, JL. "Red Cell Distribution Width and C-Reactive Protein in Predicting Mortality in Patients with Coronary Disease and in a Normal Comparison Population." CIRCULATION 122.21 (November 23, 2010).
Source
wos-lite
Published In
Circulation
Volume
122
Issue
21
Publish Date
2010

Myostatin decreases with aerobic exercise and associates with insulin resistance.

PURPOSE: There is mounting evidence that skeletal muscle produces and secretes biologically active proteins or "myokines" that facilitate metabolic cross talk between organ systems. The increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Despite these intriguing findings, there have been few studies linking myostatin and insulin resistance. METHODS: To explore this relationship in more detail, we quantified myostatin protein in muscle and plasma from 10 insulin-resistant, middle-aged (53.1 ± 5.5 yr) men before and after 6 months of moderate aerobic exercise training (1200 kcal·wk−¹ at 40%-55% VO2peak). To establish a cause-effect relationship, we also injected C57/Bl6 male mice with high physiological levels of recombinant myostatin protein. RESULTS: Myostatin protein levels were shown to decrease in muscle (37%, P = 0.042, n = 10) and matching plasma samples (from 28.7 ng·mL−¹ pretraining to 22.8 ng·mL−¹ posttraining, P = 0.003, n = 9) with aerobic exercise. Furthermore, the strong correlation between plasma myostatin levels and insulin sensitivity (R² = 0.82, P < 0.001, n = 9) suggested a cause-effect relationship that was subsequently confirmed by inducing insulin resistance in myostatin-injected mice. A modest increase (44%) in plasma myostatin levels was also associated with significant reductions in the insulin-stimulated phosphorylation of Akt (Thr308) in both muscle and liver of myostatin-treated animals. CONCLUSIONS: These findings indicate that both muscle and plasma myostatin protein levels are regulated by aerobic exercise and, furthermore, that myostatin is in the causal pathway of acquired insulin resistance with physical inactivity.

Authors
Hittel, DS; Axelson, M; Sarna, N; Shearer, J; Huffman, KM; Kraus, WE
MLA Citation
Hittel, DS, Axelson, M, Sarna, N, Shearer, J, Huffman, KM, and Kraus, WE. "Myostatin decreases with aerobic exercise and associates with insulin resistance." Med Sci Sports Exerc 42.11 (November 2010): 2023-2029.
PMID
20386333
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
42
Issue
11
Publish Date
2010
Start Page
2023
End Page
2029
DOI
10.1249/MSS.0b013e3181e0b9a8

First Demonstration that Peripheral Gene Expression as Measured by the CorusCAD Score Correlates with Coronary Arterial Plaque Burden by Quantitative Coronary Angiography and Coronary Artery Calcium Scoring

Authors
Voros, S; Elashoff, MR; Sehnert, AJ; Lieu, HD; Wingrove, JA; Daniels, SE; Rosenberg, S; Lansky, A; Schwartz, RS; Kraus, WE; Topol, EJ
MLA Citation
Voros, S, Elashoff, MR, Sehnert, AJ, Lieu, HD, Wingrove, JA, Daniels, SE, Rosenberg, S, Lansky, A, Schwartz, RS, Kraus, WE, and Topol, EJ. "First Demonstration that Peripheral Gene Expression as Measured by the CorusCAD Score Correlates with Coronary Arterial Plaque Burden by Quantitative Coronary Angiography and Coronary Artery Calcium Scoring." November 2010.
Source
wos-lite
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
30
Issue
11
Publish Date
2010
Start Page
E286
End Page
E287

Development and Validation of a Blood-Based Gene Expression Algorithm for Assessment of Obstructive Coronary Artery Disease in Nondiabetic Patients

Authors
Rosenberg, S; Elashoff, MR; Beineke, P; Daniels, SE; Wingrove, JA; Sager, PT; Tingley, WG; Schwartz, RS; Voros, S; Ellis, SG; Tahirkheli, N; Waksman, R; McPherson, JA; Lansky, AJ; Topol, EJ; Kraus, WE
MLA Citation
Rosenberg, S, Elashoff, MR, Beineke, P, Daniels, SE, Wingrove, JA, Sager, PT, Tingley, WG, Schwartz, RS, Voros, S, Ellis, SG, Tahirkheli, N, Waksman, R, McPherson, JA, Lansky, AJ, Topol, EJ, and Kraus, WE. "Development and Validation of a Blood-Based Gene Expression Algorithm for Assessment of Obstructive Coronary Artery Disease in Nondiabetic Patients." November 2010.
Source
wos-lite
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
30
Issue
11
Publish Date
2010
Start Page
E270
End Page
E270

Identification of a Gene Expression Signature for Obstructive CAD in Whole Blood Using Precise Clinical Phenotyping and Paired Microarray Analysis

Authors
Wingrove, JA; Elashoff, MR; Beineke, P; Daniels, SE; Tingley, WG; Sehnert, AJ; Yau, M; Rosenberg, S; Kraus, WE; Voros, S; Schwartz, RS; Cristea, E; Lansky, AJ; Topol, EJ; Investigators, PREDICT
MLA Citation
Wingrove, JA, Elashoff, MR, Beineke, P, Daniels, SE, Tingley, WG, Sehnert, AJ, Yau, M, Rosenberg, S, Kraus, WE, Voros, S, Schwartz, RS, Cristea, E, Lansky, AJ, Topol, EJ, and Investigators, PREDICT. "Identification of a Gene Expression Signature for Obstructive CAD in Whole Blood Using Precise Clinical Phenotyping and Paired Microarray Analysis." November 2010.
Source
wos-lite
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
30
Issue
11
Publish Date
2010
Start Page
E296
End Page
E296

Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer.

BACKGROUND: The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy. METHODS/DESIGN: Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk⁻¹ of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO₂peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO₂peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO₂peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks). DISCUSSION: EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO₂peak and other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy. TRIAL REGISTRATION: NCT01186367.

Authors
Jones, LW; Douglas, PS; Eves, ND; Marcom, PK; Kraus, WE; Herndon, JE; Inman, BA; Allen, JD; Peppercorn, J
MLA Citation
Jones, LW, Douglas, PS, Eves, ND, Marcom, PK, Kraus, WE, Herndon, JE, Inman, BA, Allen, JD, and Peppercorn, J. "Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer. (Published online)" BMC Cancer 10 (October 6, 2010): 531-.
Website
http://hdl.handle.net/10161/4358
PMID
20925920
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
531
DOI
10.1186/1471-2407-10-531

Accuracy of self-reported height and weight in a community-based sample of older African Americans and whites.

BACKGROUND: To ascertain accuracy of self-reported height, weight (and hence body mass index) in African American and white women and men older than 70 years of age. METHOD: The sample consisted of cognitively intact participants at the third in-person wave (1992-1993) of the Duke Established Populations for Epidemiologic Studies of the Elderly (age 71 and older, N = 1761; residents of five adjacent counties, one urban, four rural). During in-person, in-home interviews using trained interviewers, height and weight were self-reported (and measured later in the same visit using a standardized protocol), and information were obtained on race, sex, and age. RESULTS: Accuracy of self-reported height and weight was high (intraclass correlation coefficient 0.85 and 0.97, respectively) but differed as a function of race and age. On average, all groups overestimated their height; whereas (non-Hispanic) white men and women underestimated their weight, African Americans overestimated their weight. Overestimation of height and weight was more marked in persons 85 years and older. Specificity for overweight (body mass index [kg/m(2)] ≥ 25) and obesity (body mass index ≥ 30) ranged from 0.90 to 0.99 for African Americans and whites, but sensitivity was better for African Americans (overweight: 0.81, obesity: 0.89), than for whites (0.66 and 0.57, respectively). CONCLUSIONS: Height and weight self-reported by African Americans and whites over the age of 70 can be used in epidemiological studies, with greater caution needed for self-reports of whites, and of persons 85 years of age or older.

Authors
Fillenbaum, GG; Kuchibhatla, MN; Whitson, HE; Batch, BC; Svetkey, LP; Pieper, CF; Kraus, WE; Cohen, HJ; Blazer, DG
MLA Citation
Fillenbaum, GG, Kuchibhatla, MN, Whitson, HE, Batch, BC, Svetkey, LP, Pieper, CF, Kraus, WE, Cohen, HJ, and Blazer, DG. "Accuracy of self-reported height and weight in a community-based sample of older African Americans and whites." J Gerontol A Biol Sci Med Sci 65.10 (October 2010): 1123-1129.
PMID
20530243
Source
pubmed
Published In
Journals of Gerontology: Series A
Volume
65
Issue
10
Publish Date
2010
Start Page
1123
End Page
1129
DOI
10.1093/gerona/glq096

Reclassification of cardiovascular risk using integrated clinical and molecular biosignatures: Design of and rationale for the Measurement to Understand the Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Horizon 1 Cardiovascular Disease Study.

BACKGROUND: Clinical predictive models leave gaps in our ability to stratify cardiovascular risk. High-throughput molecular profiling promises to improve risk classification. METHODS: Horizon 1 of the Measurement to Understand the Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Study was conceived to apply emerging molecular techniques to existing data sets to characterize mechanistic diversity underlying complex human diseases, response to therapy, and prognosis. No previous studies have applied multiple, complementary molecular techniques in combination with well-developed clinical risk models to refine cardiovascular risk prediction. The MURDOCK Cardiovascular Disease Study will assess molecular profiles integrated with clinical data in "clinomic" profiles for cardiovascular risk classification. CONCLUSION: Herein, we describe the design of and rationale for the MURDOCK Cardiovascular Disease Study.

Authors
Shah, SH; Granger, CB; Hauser, ER; Kraus, WE; Sun, J-L; Pieper, K; Nelson, CL; Delong, ER; Califf, RM; Newby, LK; MURDOCK Horizon 1 Cardiovascular Disease Investigators,
MLA Citation
Shah, SH, Granger, CB, Hauser, ER, Kraus, WE, Sun, J-L, Pieper, K, Nelson, CL, Delong, ER, Califf, RM, Newby, LK, and MURDOCK Horizon 1 Cardiovascular Disease Investigators, . "Reclassification of cardiovascular risk using integrated clinical and molecular biosignatures: Design of and rationale for the Measurement to Understand the Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Horizon 1 Cardiovascular Disease Study." Am Heart J 160.3 (September 2010): 371-379.e2.
PMID
20826242
Source
pubmed
Published In
American Heart Journal
Volume
160
Issue
3
Publish Date
2010
Start Page
371
End Page
379.e2
DOI
10.1016/j.ahj.2010.06.051

Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and human association studies.

Aging is believed to be among the most important contributors to atherosclerosis, through mechanisms that remain largely obscure. Serum levels of tumor necrosis factor (TNF) rise with aging and have been correlated with the incidence of myocardial infarction. We therefore sought to determine whether genetic variation in the TNF receptor-1 gene (TNFR1) contributes to aging-related atherosclerosis in humans and whether Tnfr1 expression aggravates aging-related atherosclerosis in mice. With 1330 subjects from a coronary angiography database, we performed a case-control association study of coronary artery disease (CAD) with 16 TNFR1 single-nucleotide polymorphisms (SNPs). Two TNFR1 SNPs significantly associated with CAD in subjects >55 years old, and this association was supported by analysis of a set of 759 independent CAD cases. In multiple linear regression analysis, accounting for TNFR1 SNP rs4149573 significantly altered the relationship between aging and CAD index among 1811 subjects from the coronary angiography database. To confirm that TNFR1 contributes to aging-dependent atherosclerosis, we grafted carotid arteries from 18- and 2-month-old wild-type (WT) and Tnfr1(-/-) mice into congenic apolipoprotein E-deficient (Apoe(-/-)) mice and harvested grafts from 1 to 7 weeks post-operatively. Aged WT arteries developed accelerated atherosclerosis associated with enhanced TNFR1 expression, enhanced macrophage recruitment, reduced smooth muscle cell proliferation and collagen content, augmented apoptosis and plaque hemorrhage. In contrast, aged Tnfr1(-/-) arteries developed atherosclerosis that was indistinguishable from that in young Tnfr1(-/-) arteries and significantly less than that observed in aged WT arteries. We conclude that TNFR1 polymorphisms associate with aging-related CAD in humans, and TNFR1 contributes to aging-dependent atherosclerosis in mice.

Authors
Zhang, L; Connelly, JJ; Peppel, K; Brian, L; Shah, SH; Nelson, S; Crosslin, DR; Wang, T; Allen, A; Kraus, WE; Gregory, SG; Hauser, ER; Freedman, NJ
MLA Citation
Zhang, L, Connelly, JJ, Peppel, K, Brian, L, Shah, SH, Nelson, S, Crosslin, DR, Wang, T, Allen, A, Kraus, WE, Gregory, SG, Hauser, ER, and Freedman, NJ. "Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and human association studies." Hum Mol Genet 19.14 (July 15, 2010): 2754-2766.
PMID
20421368
Source
pubmed
Published In
Human Molecular Genetics
Volume
19
Issue
14
Publish Date
2010
Start Page
2754
End Page
2766
DOI
10.1093/hmg/ddq172

The 2008 Physical Activity Guidelines for Americans: Implications for Clinical and Public Health Practice

Authors
Pate, RR; Yancey, AK; Kraus, WE
MLA Citation
Pate, RR, Yancey, AK, and Kraus, WE. "The 2008 Physical Activity Guidelines for Americans: Implications for Clinical and Public Health Practice." American Journal of Lifestyle Medicine 4.3 (May 1, 2010): 209-217.
Source
crossref
Published In
American Journal of Lifestyle Medicine
Volume
4
Issue
3
Publish Date
2010
Start Page
209
End Page
217
DOI
10.1177/1559827609353300

ACTN3 Genotype Effects on Skeletal Muscle Gene Expression

Authors
Hubal, MJ; Devaney, JM; Huffman, KM; Hoffman, EP; Kraus, WE
MLA Citation
Hubal, MJ, Devaney, JM, Huffman, KM, Hoffman, EP, and Kraus, WE. "ACTN3 Genotype Effects on Skeletal Muscle Gene Expression." May 2010.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
42
Issue
5
Publish Date
2010
Start Page
87
End Page
88

The Effect of Aerobic versus Resistance Training on Insulin Action in Overweight and Obese Adults STRRIDE AT/RT: A Randomized Controlled Trial

Authors
Tanner, CJ; Slentz, CA; Kraus, WE; Bateman, LA; Willis, LH; Shields, T; Houmard, JA
MLA Citation
Tanner, CJ, Slentz, CA, Kraus, WE, Bateman, LA, Willis, LH, Shields, T, and Houmard, JA. "The Effect of Aerobic versus Resistance Training on Insulin Action in Overweight and Obese Adults STRRIDE AT/RT: A Randomized Controlled Trial." May 2010.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
42
Issue
5
Publish Date
2010
Start Page
805
End Page
806

The 1p13.3 LDL-Associated Locus Shows Large Effect Sizes in Young Populations

Authors
Devaney, JM; Thompson, PD; Visich, PS; Gordon, PM; Orkunoglu-Suer, F; Gordish-Dressman, H; Khianey, R; Hubal, MJ; Clarkson, PM; Pescatello, LS; Zoeller, RF; Kraus, WE; Hoffman, EP
MLA Citation
Devaney, JM, Thompson, PD, Visich, PS, Gordon, PM, Orkunoglu-Suer, F, Gordish-Dressman, H, Khianey, R, Hubal, MJ, Clarkson, PM, Pescatello, LS, Zoeller, RF, Kraus, WE, and Hoffman, EP. "The 1p13.3 LDL-Associated Locus Shows Large Effect Sizes in Young Populations." May 2010.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
42
Issue
5
Publish Date
2010
Start Page
796
End Page
796

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design.

BACKGROUND: The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. METHODS/DESIGN: Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. DISCUSSION: VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. TRIAL REGISTRATION: NCT00018255.

Authors
Jones, LW; Eves, ND; Kraus, WE; Potti, A; Crawford, J; Blumenthal, JA; Peterson, BL; Douglas, PS
MLA Citation
Jones, LW, Eves, ND, Kraus, WE, Potti, A, Crawford, J, Blumenthal, JA, Peterson, BL, and Douglas, PS. "The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design. (Published online)" BMC Cancer 10 (April 21, 2010): 155-.
Website
http://hdl.handle.net/10161/4354
PMID
20409311
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
155
DOI
10.1186/1471-2407-10-155

Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.

BACKGROUND: Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events. METHODS AND RESULTS: We performed mass-spectrometry-based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls ("initial"), and 140 CAD cases and 140 controls ("replication"). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined ("event" group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled ("event-replication" group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis-derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial P=0.002, replication P=0.01), and 1 comprising urea cycle metabolites (factor 9, initial P=0.0004, replication P=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74; P=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87; P=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91; P=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91; P=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84; P=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14; P=0.01). CONCLUSIONS: Metabolite profiles are associated with CAD and subsequent cardiovascular events.

Authors
Shah, SH; Bain, JR; Muehlbauer, MJ; Stevens, RD; Crosslin, DR; Haynes, C; Dungan, J; Newby, LK; Hauser, ER; Ginsburg, GS; Newgard, CB; Kraus, WE
MLA Citation
Shah, SH, Bain, JR, Muehlbauer, MJ, Stevens, RD, Crosslin, DR, Haynes, C, Dungan, J, Newby, LK, Hauser, ER, Ginsburg, GS, Newgard, CB, and Kraus, WE. "Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events." Circ Cardiovasc Genet 3.2 (April 2010): 207-214.
Website
http://hdl.handle.net/10161/5964
PMID
20173117
Source
pubmed
Published In
Circulation: Cardiovascular Genetics
Volume
3
Issue
2
Publish Date
2010
Start Page
207
End Page
214
DOI
10.1161/CIRCGENETICS.109.852814

EXERCISE TRAINING AND IMPLANTABLE CARDIOVERTER DEFIBRILLATOR SHOCKS IN PATIENTS WITH HEART FAILURE: RESULTS FROM HF-ACTION

Authors
Piccini, JP; Hellkamp, AS; Whellan, DJ; Ellis, SJ; Keteyian, SJ; Cooper, L; Kraus, WE; Pina, IL; O'Connor, CM
MLA Citation
Piccini, JP, Hellkamp, AS, Whellan, DJ, Ellis, SJ, Keteyian, SJ, Cooper, L, Kraus, WE, Pina, IL, and O'Connor, CM. "EXERCISE TRAINING AND IMPLANTABLE CARDIOVERTER DEFIBRILLATOR SHOCKS IN PATIENTS WITH HEART FAILURE: RESULTS FROM HF-ACTION." March 9, 2010.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
55
Issue
10
Publish Date
2010

Genome-wide linkage analysis of quantitative biomarker traits of osteoarthritis in a large, multigenerational extended family.

OBJECTIVE: The genetic contributions to the multifactorial disorder osteoarthritis (OA) have been increasingly recognized. The goal of the current study was to use OA-related biomarkers of severity and disease burden as quantitative traits to identify genetic susceptibility loci for OA. METHODS: In a large multigenerational extended family (n = 350), we measured 5 OA-related biomarkers: hyaluronan (HA), cartilage oligomeric matrix protein (COMP), N-propeptide of type IIA collagen (PIIANP), C-propeptide of type II procollagen (CPII), and type II collagen neoepitope (C2C). Single-nucleotide polymorphism markers (n = 6,090) covering the whole genome were genotyped using the Illumina HumanLinkage-12 BeadChip. Variance components analysis, as implemented in the Sequential Oligogenic Linkage Analysis Routines, was used to estimate heritabilities of the quantitative traits and to calculate 2-point and multipoint logarithm of odds (LOD) scores using a polygenic model. RESULTS: After adjusting for age and sex, we found that 4 of the 5 biomarkers exhibited significant heritability (PIIANP 0.57, HA 0.49, COMP 0.43, C2C 0.30; P < or = 0.01 for all). Fourteen of the 19 loci that had multipoint LOD scores of >1.5 were near to or overlapped with previously reported OA susceptibility loci. Four of these loci were identified by more than 1 biomarker. The maximum multipoint LOD scores for the heritable quantitative biomarker traits were 4.3 for PIIANP (chromosome 8p23.2), 3.2 for COMP (chromosome 8q11.1), 2.0 for HA (chromosome 6q16.3), and 2.0 for C2C (chromosome 5q31.2). CONCLUSION: Herein, we report the first evidence of genetic susceptibility loci identified by OA-related biomarkers in an extended family. Our results demonstrate that serum concentrations of PIIANP, HA, COMP, and C2C have substantial heritable components, and using these biomarkers, several genetic loci potentially contributing to the genetic diversity of OA were identified.

Authors
Chen, H-C; Kraus, VB; Li, Y-J; Nelson, S; Haynes, C; Johnson, J; Stabler, T; Hauser, ER; Gregory, SG; Kraus, WE; Shah, SH
MLA Citation
Chen, H-C, Kraus, VB, Li, Y-J, Nelson, S, Haynes, C, Johnson, J, Stabler, T, Hauser, ER, Gregory, SG, Kraus, WE, and Shah, SH. "Genome-wide linkage analysis of quantitative biomarker traits of osteoarthritis in a large, multigenerational extended family." Arthritis Rheum 62.3 (March 2010): 781-790.
PMID
20187133
Source
pubmed
Published In
Arthritis and Rheumatism
Volume
62
Issue
3
Publish Date
2010
Start Page
781
End Page
790
DOI
10.1002/art.27288

Enhancing standard cardiac rehabilitation with stress management training: background, methods, and design for the enhanced study.

PURPOSE: Enhancing Standard Cardiac Rehabilitation with Stress Management Training in Patients with Heart Disease (ENHANCED) is a randomized clinical trial funded by the National Heart Lung and Blood Institute to evaluate the effects of stress management training (SMT) on changes in biomarkers of risk and quality of life for patients enrolled in traditional exercise-based cardiac rehabilitation (CR). METHODS: One hundred fifty cardiac patients recruited from Duke University and the University of North Carolina will be evaluated and randomized to CR enhanced by SMT (including sessions devoted to relaxation training, cognitive restructuring, communication skills, and problem solving) or to standard exercise-based CR. Before and after 12 weeks of treatment, patients will undergo a battery of psychometric questionnaires and evaluation of cardiovascular biomarkers, including measures of flow-mediated dilation, heart rate variability, baroreflex sensitivity, platelet function and inflammation, and ischemia during laboratory mental stress testing. The primary outcomes include a composite measure of stress (distress, depression, anxiety, and hostility and 24-hour urinary catecholamines and cortisol) and a composite measure of cardiac biomarkers of risk (vascular endothelial function, cardiac vagal control, inflammation, platelet function, and mental stress-induced myocardial ischemia). Secondary outcomes include measures of quality of life as well as clinical events, including death, hospitalizations, myocardial infarction, and revascularization procedures. RESULTS: This article reviews prior studies in the area and describes the design of the ENHANCED study. Several key methodological issues are discussed including the assessment of biomarkers of risk and barriers to the integration of SMT into traditional CR. CONCLUSIONS: The ENHANCED study will provide important information by determining to what extent SMT combined with exercise-based CR may improve prognosis and quality of life in vulnerable cardiac patients.

Authors
Blumenthal, JA; Wang, JT; Babyak, M; Watkins, L; Kraus, W; Miller, P; Hinderliter, A; Sherwood, A
MLA Citation
Blumenthal, JA, Wang, JT, Babyak, M, Watkins, L, Kraus, W, Miller, P, Hinderliter, A, and Sherwood, A. "Enhancing standard cardiac rehabilitation with stress management training: background, methods, and design for the enhanced study." J Cardiopulm Rehabil Prev 30.2 (March 2010): 77-84.
PMID
20216360
Source
pubmed
Published In
Journal of Cardiopulmonary Rehabilitation and Prevention
Volume
30
Issue
2
Publish Date
2010
Start Page
77
End Page
84
DOI
10.1097/HCR.0b013e3181d0c1d3

Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma.

BACKGROUND: The study was undertaken to evaluate cardiorespiratory fitness, skeletal muscle function, and body composition of patients with newly diagnosed and untreated, postsurgical primary malignant glioma. METHODS: By using a cross-sectional design, patients with clinically stable (10 +/- 7 days postsurgery) high-grade glioma (HGG; n = 25) or low-grade glioma (LGG; n = 10) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess cardiorespiratory fitness (peak oxygen consumption, VO2peak). Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain scale. RESULTS: CPET was a feasible and safe procedure to assess VO2peak, with no serious adverse events. VO2peak indexed to total body weight and lean body mass (LBM) for both groups was 13.0 mL x weight x min(-1) and 19 mL x LBM x min(-1), the equivalent to 59% and 38% below age- and sex-predicted normative values, respectively. Skeletal muscle strength and mid-thigh CSA were lower in HGG relative to LGG patients (83 vs 125 Nm, P = .025; 94 vs 119 cm2, P = .171, respectively). Skeletal muscle isokinetic strength, CSA, and body composition outcomes predicted VO2peak (r = -0.59 to 0.68, P < .05). CONCLUSIONS: Postsurgical glioma patients have markedly reduced cardiorespiratory fitness, isokinetic strength, and CSA. Prospective studies are now required to determine whether such abnormalities influence treatment toxicity and clinical outcome as well as to test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction.

Authors
Jones, LW; Friedman, AH; West, MJ; Mabe, SK; Fraser, J; Kraus, WE; Friedman, HS; Tresch, MI; Major, N; Reardon, DA
MLA Citation
Jones, LW, Friedman, AH, West, MJ, Mabe, SK, Fraser, J, Kraus, WE, Friedman, HS, Tresch, MI, Major, N, and Reardon, DA. "Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma." Cancer 116.3 (February 1, 2010): 695-704.
PMID
20029975
Source
pubmed
Published In
Cancer
Volume
116
Issue
3
Publish Date
2010
Start Page
695
End Page
704
DOI
10.1002/cncr.24808

Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study.

PURPOSE: To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. METHODS: Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO(2peak)) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy-Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. RESULTS: Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO(2peak) and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values < .05). CONCLUSIONS: Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.

Authors
Jones, LW; Mourtzakis, M; Peters, KB; Friedman, AH; West, MJ; Mabe, SK; Kraus, WE; Friedman, HS; Reardon, DA
MLA Citation
Jones, LW, Mourtzakis, M, Peters, KB, Friedman, AH, West, MJ, Mabe, SK, Kraus, WE, Friedman, HS, and Reardon, DA. "Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study." Oncologist 15.6 (2010): 636-647.
PMID
20484122
Source
pubmed
Published In
The oncologist
Volume
15
Issue
6
Publish Date
2010
Start Page
636
End Page
647
DOI
10.1634/theoncologist.2009-0265

Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients

Background: Diagnosing obstructive coronary artery disease (CAD) in at-risk patients can be challenging and typically requires both noninvasive imaging methods and coronary angiography, the gold standard. Previous studies have suggested that peripheral blood gene expression can indicate the presence of CAD. Objective: To validate a previously developed 23-gene, expression-based classification test for diagnosis of obstructive CAD in nondiabetic patients. Design: Multicenter prospective trial with blood samples obtained before coronary angiography. (ClinicalTrials.gov registration number: NCT00500617) Setting: 39 centers in the United States. Patients: An independent validation cohort of 526 nondiabetic patients with a clinical indication for coronary angiography. Measurements: Receiver-operating characteristic (ROC) analysis of classifier score measured by real-time polymerase chain reaction, additivity to clinical factors, and reclassification of patient disease likelihood versus disease status defined by quantitative coronary angiography. Obstructive CAD was defined as 50% or greater stenosis in 1 or more major coronary arteries by quantitative coronary angiography. Results: The area under the ROC curve (AUC) was 0.70 ± 0.02 (P < 0.001); the test added to clinical variables (Diamond-Forrester method) (AUC, 0.72 with the test vs. 0.66 without; P = 0.003) and added somewhat to an expanded clinical model (AUC, 0.745 with the test vs. 0.732 without; P = 0.089). The test improved net reclassification over both the Diamond-Forrester method and the expanded clinical model (P < 0.001). At a score threshold that corresponded to a 20% likelihood of obstructive CAD (14.75), the sensitivity and specificity were 85% and 43% (yielding a negative predictive value of 83% and a positive predictive value of 46%), with 33% of patient scores below this threshold. Limitation: Patients with chronic inflammatory disorders, elevated levels of leukocytes or cardiac protein markers, or diabetes were excluded. Conclusion: A noninvasive whole-blood test based on gene expression and demographic characteristics may be useful for assessing obstructive CAD in nondiabetic patients without known CAD. Primary Funding Source: CardioDx. © 2010 American College of Physicians.

Authors
Rosenberg, S; Elashoff, MR; Beineke, P; Daniels, SE; Wingrove, JA; Tingley, WG; Sager, PT; Sehnert, AJ; Yau, M; Kraus, WE; Newby, LK; Schwartz, RS; Voros, S; Ellis, SG; Tahirkheli, N; Waksman, R; McPherson, J; Lansky, A; Winn, ME; Schork, NJ; Topol, EJ
MLA Citation
Rosenberg, S, Elashoff, MR, Beineke, P, Daniels, SE, Wingrove, JA, Tingley, WG, Sager, PT, Sehnert, AJ, Yau, M, Kraus, WE, Newby, LK, Schwartz, RS, Voros, S, Ellis, SG, Tahirkheli, N, Waksman, R, McPherson, J, Lansky, A, Winn, ME, Schork, NJ, and Topol, EJ. "Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients." Annals of Internal Medicine 153.7 (2010): 425-434.
PMID
20921541
Source
scival
Published In
Annals of internal medicine
Volume
153
Issue
7
Publish Date
2010
Start Page
425
End Page
434
DOI
10.7326/0003-4819-153-7-201010050-00005

Interventions to promote physical activity and dietary lifestyle changes for cardiovascular risk factor reduction in adults: A scientific statement from the american heart association

Authors
Artinian, NT; Fletcher, GF; Mozaffarian, D; Kris-Etherton, P; Horn, LV; Lichtenstein, AH; Kumanyika, S; Kraus, WE; Fleg, JL; Redeker, NS; Meininger, JC; Banks, J; Stuart-Shor, EM; Fletcher, BJ; Miller, TD; Hughes, S; Braun, LT; Kopin, LA; Berra, K; Hayman, LL; Ewing, LJ; Ades, PA; Durstine, JL; Houston-Miller, N; Burke, LE
MLA Citation
Artinian, NT, Fletcher, GF, Mozaffarian, D, Kris-Etherton, P, Horn, LV, Lichtenstein, AH, Kumanyika, S, Kraus, WE, Fleg, JL, Redeker, NS, Meininger, JC, Banks, J, Stuart-Shor, EM, Fletcher, BJ, Miller, TD, Hughes, S, Braun, LT, Kopin, LA, Berra, K, Hayman, LL, Ewing, LJ, Ades, PA, Durstine, JL, Houston-Miller, N, and Burke, LE. "Interventions to promote physical activity and dietary lifestyle changes for cardiovascular risk factor reduction in adults: A scientific statement from the american heart association." Circulation 122.4 (2010): 406-441.
PMID
20625115
Source
scival
Published In
Circulation
Volume
122
Issue
4
Publish Date
2010
Start Page
406
End Page
441
DOI
10.1161/CIR.0b013e3181e8edf1

Validation of a Gender-Dependent Blood-Based Gene Expression Test for Diagnosis of Obstructive Coronary Artery Disease in Non-Diabetic Patients

Authors
Garrett, B; Wingrove, JA; Elashoff, MR; Daniels, SE; Rosenberg, S; Kraus, WE; Voros, S; Schwartz, RS; Topol, EJ
MLA Citation
Garrett, B, Wingrove, JA, Elashoff, MR, Daniels, SE, Rosenberg, S, Kraus, WE, Voros, S, Schwartz, RS, and Topol, EJ. "Validation of a Gender-Dependent Blood-Based Gene Expression Test for Diagnosis of Obstructive Coronary Artery Disease in Non-Diabetic Patients." JOURNAL OF CARDIOVASCULAR NURSING 25.5 (2010): 365-366.
Source
wos-lite
Published In
Journal of Cardiovascular Nursing
Volume
25
Issue
5
Publish Date
2010
Start Page
365
End Page
366

Exercise training, lipid regulation, and insulin action: a tangled web of cause and effect.

Lipids are a strong mediator of coronary artery disease and cardiovascular risk. Although the effects of exercise to improve high-density lipoprotein (HDL) cholesterol and serum triglycerides (TGs) have been known for some time, the effects of different amounts and intensities of exercise on fasting and postprandial serum lipids are little understood. Normal lipid physiology is perturbed in insulin resistant states, where inhibition of lipolysis is impaired, particularly in the postprandial period when excursions in insulin and serum TGs are particularly high. In our STRRIDE (Studies of a Targeted Risk Reduction Intervention through Defined Exercise) study, three important metabolic cardiovascular risk-related variables were improved more by moderate intensity than vigorous-intensity exercise. Moderate-intensity exercise was significantly more effective at lowering TGs and improving insulin sensitivity than was vigorous exercise. Additionally, a composite score for metabolic syndrome improved significantly with low-amount/moderate, but did not with low-amount/vigorous-intensity exercise. That all three of these strong, independent, cardiovascular risk factors were significantly affected by moderate-intensity exercise suggests that regular walking exercise might be as effective, if not more so, than more vigorous exercise in favorably modifying cardiovascular risk. Despite the impressive effects of regular exercise on fasting lipids and atherogenic dyslipidemia, they are more impressive when compared with the trajectory of changes that occur in individuals that remain inactive, without regular exposure to regular exercise. A scientific priority for future investigations should be to study the independent and combined effects of exercise intensity and amount on exercise responses through a direct comparison between two groups matched on amount but differing in intensity.

Authors
Kraus, WE; Slentz, CA
MLA Citation
Kraus, WE, and Slentz, CA. "Exercise training, lipid regulation, and insulin action: a tangled web of cause and effect." Obesity (Silver Spring) 17 Suppl 3 (December 2009): S21-S26. (Review)
PMID
19927141
Source
pubmed
Published In
Obesity
Volume
17 Suppl 3
Publish Date
2009
Start Page
S21
End Page
S26
DOI
10.1038/oby.2009.384

Exercise, abdominal obesity, skeletal muscle, and metabolic risk: evidence for a dose response.

The obese are at increased risk for cardiovascular disease and type 2 diabetes. However, some who are obese have no metabolic abnormalities. So, it is not adipose tissue per se, but perhaps where it is located that is important for determining metabolic consequences. Regular exercise is known to reduce risk for metabolic disease through numerous mechanisms. The purpose of this report is to highlight some of the efficacy-based data on the effects of exercise (and also a sedentary lifestyle) on abdominal obesity, visceral fat, and metabolic risk. We also discuss how impaired fatty acid oxidation (FAO) in skeletal muscle may be related to both insulin resistance and a contributor to weight gain. In summary, it is evident that exercise in sufficient amounts can lead to substantial decreases in body weight, total body fat, and visceral fat. Additionally, evidence now supports the conclusion that there is a dose-response relationship between exercise amount and these changes, i.e., more exercise leads to additional benefits. Additionally, there are a number of important cardiometabolic risk factors that were most favorably effected by moderate-intensity compared to vigorous-intensity exercise. Unfortunately, it is also apparent that in sedentary middle-aged men and women, short periods of physical inactivity lead to significant weight gain, substantial increases in visceral fat, and further metabolic deterioration. Finally, favorable modulation of mitochondrial oxidative capacity in skeletal muscle by exercise training may reduce a block for complete oxidation of fatty acids in muscle and thereby relieve a block to effective insulin signaling.

Authors
Slentz, CA; Houmard, JA; Kraus, WE
MLA Citation
Slentz, CA, Houmard, JA, and Kraus, WE. "Exercise, abdominal obesity, skeletal muscle, and metabolic risk: evidence for a dose response." Obesity (Silver Spring) 17 Suppl 3 (December 2009): S27-S33. (Review)
PMID
19927142
Source
pubmed
Published In
Obesity
Volume
17 Suppl 3
Publish Date
2009
Start Page
S27
End Page
S33
DOI
10.1038/oby.2009.385

Plasma Metabolomic Profiles Predict Future Cardiovascular Events

Authors
Shah, SH; Sun, J-L; Pieper, K; Crosslin, DR; Haynes, C; Bain, JR; Muehlbauer, M; Stevens, RD; Hauser, ER; Kraus, WE; Newgard, CB; Granger, CB; Califf, RM; Newby, LK
MLA Citation
Shah, SH, Sun, J-L, Pieper, K, Crosslin, DR, Haynes, C, Bain, JR, Muehlbauer, M, Stevens, RD, Hauser, ER, Kraus, WE, Newgard, CB, Granger, CB, Califf, RM, and Newby, LK. "Plasma Metabolomic Profiles Predict Future Cardiovascular Events." November 3, 2009.
Source
wos-lite
Published In
Circulation
Volume
120
Issue
18
Publish Date
2009
Start Page
S466
End Page
S467

Red Cell Distribution Width (RDW) is a Strong Predictor of Outcome and is Weakly Associated With Clinical Variables in Patients at Risk for Cardiovascular Events

Authors
Newby, LK; Shah, SH; Sun, J-L; Pieper, K; Hauser, ER; Kraus, WE; Granger, CB
MLA Citation
Newby, LK, Shah, SH, Sun, J-L, Pieper, K, Hauser, ER, Kraus, WE, and Granger, CB. "Red Cell Distribution Width (RDW) is a Strong Predictor of Outcome and is Weakly Associated With Clinical Variables in Patients at Risk for Cardiovascular Events." November 3, 2009.
Source
wos-lite
Published In
Circulation
Volume
120
Issue
18
Publish Date
2009
Start Page
S1174
End Page
S1174

Development and Multi-Center Validation of a Blood-based Gene Expression Test for Diagnosis of Obstructive CAD in Non-Diabetic Patients

Authors
Kraus, WE; Rosenberg, S; Elashoff, MR; Beineke, P; Daniels, SE; Wingrove, JA; Tingley, WG; Sager, P; Schwartz, RS; Voros, S; Ellis, S; Tahirkheli, N; Waksman, R; McPherson, J; Topol, EJ; Investigators, PREDICT
MLA Citation
Kraus, WE, Rosenberg, S, Elashoff, MR, Beineke, P, Daniels, SE, Wingrove, JA, Tingley, WG, Sager, P, Schwartz, RS, Voros, S, Ellis, S, Tahirkheli, N, Waksman, R, McPherson, J, Topol, EJ, and Investigators, PREDICT. "Development and Multi-Center Validation of a Blood-based Gene Expression Test for Diagnosis of Obstructive CAD in Non-Diabetic Patients." November 3, 2009.
Source
wos-lite
Published In
Circulation
Volume
120
Issue
18
Publish Date
2009
Start Page
S563
End Page
S563

Impact of Age on Aerobic Capacity in Patients With Systolic Heart Failure: The HF-ACTION Study

Authors
Forman, DE; Clare, R; Kitzman, DW; Ellis, SJ; Chiara, T; Fletcher, G; Fleg, JL; Kraus, WE
MLA Citation
Forman, DE, Clare, R, Kitzman, DW, Ellis, SJ, Chiara, T, Fletcher, G, Fleg, JL, and Kraus, WE. "Impact of Age on Aerobic Capacity in Patients With Systolic Heart Failure: The HF-ACTION Study." November 3, 2009.
Source
wos-lite
Published In
Circulation
Volume
120
Issue
18
Publish Date
2009
Start Page
S550
End Page
S550

Impact of Promoter and 9p21 Single Nucleotide Polymorphisms on Peripheral Blood Cell Expression of Genes Responsive to Levels of Obstructive Coronary Disease

Authors
Wingrove, JA; Tao, H; Daniels, SE; Rosenberg, S; Kraus, WE; Schwartz, RS; Voros, S; Topol, EJ; Investigators, PREDICT
MLA Citation
Wingrove, JA, Tao, H, Daniels, SE, Rosenberg, S, Kraus, WE, Schwartz, RS, Voros, S, Topol, EJ, and Investigators, PREDICT. "Impact of Promoter and 9p21 Single Nucleotide Polymorphisms on Peripheral Blood Cell Expression of Genes Responsive to Levels of Obstructive Coronary Disease." November 3, 2009.
Source
wos-lite
Published In
Circulation
Volume
120
Issue
18
Publish Date
2009
Start Page
S564
End Page
S564

Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking.

The CATHGEN study reported associations of chromosome 3q13-21 genes (KALRN, MYLK, CDGAP, and GATA2) with early-onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDGAP (rs10934490, p = 0.019, OR = 1.6) and KALRN (rs12637456, p = 0.011, OR = 2.0) and suggestive association was found in MYLK (rs16834871, p = 0.051, OR = 1.8, adjusting for gender). No SNP association was found among non-smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p = 0.017) and KALRN (rs12637456, p = 0.010). Similar differences in SNP effects by smoking status were observed on re-analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.

Authors
Horne, BD; Hauser, ER; Wang, L; Muhlestein, JB; Anderson, JL; Carlquist, JF; Shah, SH; Kraus, WE
MLA Citation
Horne, BD, Hauser, ER, Wang, L, Muhlestein, JB, Anderson, JL, Carlquist, JF, Shah, SH, and Kraus, WE. "Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking." Ann Hum Genet 73.Pt 6 (November 2009): 551-558.
PMID
19706030
Source
pubmed
Published In
Annals of Human Genetics
Volume
73
Issue
Pt 6
Publish Date
2009
Start Page
551
End Page
558
DOI
10.1111/j.1469-1809.2009.00540.x

Rationale and design of the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository.

BACKGROUND: Disturbances in cardiac rhythm can lead to significant morbidity and mortality. Many arrhythmias are known to have a heritable component, but the degree to which genetic variation contributes to disease risk and morbidity is poorly understood. METHODS AND RESULTS: The EPGEN is a prospective single-center repository that archives DNA, RNA, and protein samples obtained at the time of an electrophysiologic evaluation or intervention. To identify genes and molecular variants that are associated with risk for arrhythmic phenotypes, EPGEN uses unbiased genomic screening; candidate gene analysis; and both unbiased and targeted transcript, protein, and metabolite profiling. To date, EPGEN has successfully enrolled >1,500 subjects. The median age of the study population is 62.9 years; 35% of the subjects are female and 21% are black. To this point, the study population has been composed of patients who had undergone defibrillator (implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator) implantation (45%), electrophysiology studies or ablation procedures (35%), and pacemaker implantation or other procedures (20%). The cohort has a high prevalence of comorbidities, including diabetes (33%), hypertension (73%), chronic kidney disease (26%), and peripheral vascular disease (13%). CONCLUSIONS: We have established a biorepository and clinical database composed of patients with electrophysiologic diseases. EPGEN will seek to (1) improve risk stratification, (2) elucidate mechanisms of arrhythmogenesis, and (3) identify novel pharmacologic targets for the treatment of heart rhythm disorders.

Authors
Koontz, JI; Haithcock, D; Cumbea, V; Waldron, A; Stricker, K; Hughes, A; Nilsson, K; Sun, A; Piccini, JP; Kraus, WE; Pitt, GS; Shah, SH; Hranitzky, P
MLA Citation
Koontz, JI, Haithcock, D, Cumbea, V, Waldron, A, Stricker, K, Hughes, A, Nilsson, K, Sun, A, Piccini, JP, Kraus, WE, Pitt, GS, Shah, SH, and Hranitzky, P. "Rationale and design of the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository." Am Heart J 158.5 (November 2009): 719-725.
PMID
19853688
Source
pubmed
Published In
American Heart Journal
Volume
158
Issue
5
Publish Date
2009
Start Page
719
End Page
725
DOI
10.1016/j.ahj.2009.08.011

Relationship of Baseline Gated Rest SPECT Myocardial Perfusion Imaging to Death and Hospitalization in Heart Failure Patients: Results from the Nuclear Substudy of the HF-ACTION Trial

Authors
Atchley, AE; Kitzman, DW; Whellan, DJ; Iskandrian, AE; Ellis, SJ; Shaw, LK; Pagnanelli, RA; Kao, A; Abdul-Nour, K; Ewald, G; O'Connor, CM; Kraus, WE; Borges-Neto, S; Investigators, HF-ACTIONT
MLA Citation
Atchley, AE, Kitzman, DW, Whellan, DJ, Iskandrian, AE, Ellis, SJ, Shaw, LK, Pagnanelli, RA, Kao, A, Abdul-Nour, K, Ewald, G, O'Connor, CM, Kraus, WE, Borges-Neto, S, and Investigators, HF-ACTIONT. "Relationship of Baseline Gated Rest SPECT Myocardial Perfusion Imaging to Death and Hospitalization in Heart Failure Patients: Results from the Nuclear Substudy of the HF-ACTION Trial." JOURNAL OF CARDIAC FAILURE 15.9 (November 2009): 814-814.
Source
wos-lite
Published In
Journal of Cardiac Failure
Volume
15
Issue
9
Publish Date
2009
Start Page
814
End Page
814

Effects of exercise training intensity on pancreatic beta-cell function.

OBJECTIVE: Insulin resistance and beta-cell dysfunction both are important contributors to the pathogenesis of type 2 diabetes. Exercise training improves insulin sensitivity, but its effects on beta-cell function are less well studied. RESEARCH DESIGN AND METHODS: Sedentary, overweight adults were randomized to control or one of three 8-month exercise programs: 1) low amount/moderate intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous intensity. Of 387 randomized, 260 completed the study and 237 had complete data. Insulin sensitivity (S(i)), acute insulin response to glucose (AIRg), and the disposition index (DI = S(i) x AIRg) were modeled from an intravenous glucose tolerance test. RESULTS: Compared with control subjects, all three training programs led to increases in DI. However, the moderate-intensity group experienced a significantly larger increase in DI than either of the vigorous-intensity groups and through a different mechanism. The high-amount/vigorous-intensity group improved S(i) and had a compensatory reduction in AIRg, whereas the moderate-intensity group had a similar improvement in S(i) but almost no reduction in AIRg. Importantly, the inactive control group experienced a significant increase in fasting glucose. CONCLUSIONS: To the extent that the DI accurately reflects beta-cell function, we observed that both moderate- and vigorous-intensity exercise training improved beta-cell function, albeit through distinct mechanisms. It is not clear which of these mechanisms is preferable for maintenance of metabolic health. While moderate-intensity exercise led to a larger improvement in DI, which may reflect a transition toward a more normal DI, longer-term investigations would be necessary to determine which was more effective at reducing diabetes risk.

Authors
Slentz, CA; Tanner, CJ; Bateman, LA; Durheim, MT; Huffman, KM; Houmard, JA; Kraus, WE
MLA Citation
Slentz, CA, Tanner, CJ, Bateman, LA, Durheim, MT, Huffman, KM, Houmard, JA, and Kraus, WE. "Effects of exercise training intensity on pancreatic beta-cell function." Diabetes Care 32.10 (October 2009): 1807-1811.
PMID
19592624
Source
pubmed
Published In
Diabetes Care
Volume
32
Issue
10
Publish Date
2009
Start Page
1807
End Page
1811
DOI
10.2337/dc09-0032

Myocardial perfusion, function, and dyssynchrony in patients with heart failure: baseline results from the single-photon emission computed tomography imaging ancillary study of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) Trial.

BACKGROUND: There are currently limited data on the relationships between resting perfusion abnormalities, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, and exercise capacity as defined by peak VO(2) and 6-minute walk test in patients with heart failure (HF) and reduced LVEF. Furthermore, the association between resting perfusion abnormalities and left ventricular dyssynchrony is currently unknown. This article addresses the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) gated SPECT imaging (gSPECT) substudy baseline results. METHODS: HF-ACTION was a multicenter, randomized controlled trial of aerobic exercise training versus usual care in 2,331 stable patients with LVEF of < or = 35% and NYHA class II to IV HF symptoms treated with optimal medical therapy. Subjects enrolled in the HF-ACTION substudy underwent resting Tc-99m tetrofosmin gSPECT at baseline (n = 240). Images were evaluated for extent and severity of perfusion abnormalities using a 17-segment and a 5-degree gradation severity score (summed rest score [SRS]). Left ventricular function and dyssynchrony were assessed using validated available commercial software. RESULTS: The average age of patients enrolled was 59, 69% were male, 63% were white, and 33% were African American. Of the 240 participants, 129 (54%) were ischemic and 111 (46%) were nonischemic in etiology. The median LVEF by gSPECT for the entire cohort was 26%. Among the nuclear variables, there was a modest correlation between LVEF and SRS (r = -0.31, P < .0001) and there were stronger correlations between phase SD and SRS (r = 0.66, P < .0001) as well as phase SD and LVEF (r = -0.50, P < .0001). Patients with NYHA class III symptoms had more severe and significant degrees of dyssynchrony (median phase SD 54 degrees ) than those with NYHA class II symptoms (median phase SD 39 degrees, P = .001). Patients with an ischemic etiology had a higher SRS (P < .0001) and significantly more dyssynchrony (P < .0001) than those who were nonischemic. However, there was no difference in LVEF or objective measures of exercise capacity between these groups. With respect to peak VO(2), there was a weak correlation with LVEF (r = 0.18, P = .006) and no correlation with SRS (r = -0.04, P = 0.59) or with dyssynchrony (r = -0.13, P = .09). A weak but statistically significant correlation between SRS and 6-minute walk was observed (r = -0.15, P = .047). CONCLUSIONS: Gated SPECT imaging can provide important information in patients with HF due to severe LV dysfunction including quantitative measures of global systolic function, perfusion, and dyssynchrony. These measurements are modestly but significantly related to symptom severity and objective measures of exercise capacity.

Authors
Atchley, AE; Kitzman, DW; Whellan, DJ; Iskandrian, AE; Ellis, SJ; Pagnanelli, RA; Kao, A; Abdul-Nour, K; O'Connor, CM; Ewald, G; Kraus, WE; Borges-Neto, S; HF-ACTION Investigators,
MLA Citation
Atchley, AE, Kitzman, DW, Whellan, DJ, Iskandrian, AE, Ellis, SJ, Pagnanelli, RA, Kao, A, Abdul-Nour, K, O'Connor, CM, Ewald, G, Kraus, WE, Borges-Neto, S, and HF-ACTION Investigators, . "Myocardial perfusion, function, and dyssynchrony in patients with heart failure: baseline results from the single-photon emission computed tomography imaging ancillary study of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) Trial." Am Heart J 158.4 Suppl (October 2009): S53-S63.
PMID
19782789
Source
pubmed
Published In
American Heart Journal
Volume
158
Issue
4 Suppl
Publish Date
2009
Start Page
S53
End Page
S63
DOI
10.1016/j.ahj.2009.07.009

N-terminal pro-brain natriuretic peptide and exercise capacity in chronic heart failure: data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study.

OBJECTIVES: To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure. BACKGROUND: Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied. METHODS: We analyzed the relationship between baseline NT-proBNP and peak oxygen uptake (peak VO(2)) or distance in the 6-minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak Vo(2) or distance in the 6-minute walk test in the context of other clinical variables. Receiver operator curve analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO(2) <12 mL/kg per minute. RESULTS: NT-proBNP was the most powerful predictor of peak VO(2) (partial R(2) = 0.13, P < .0001) of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6-minute walk test, this relationship was weaker than that for peak VO(2) (partial R(2) = 0.02, P < .0001). For both peak VO(2) and distance in the 6-minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. Receiver operator curve analysis suggested NT-proBNP had moderate ability to identify patients with peak VO(2) <12 mL/kg per minute (c-index, 0.69). CONCLUSIONS: In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO(2) and a significant predictor of distance in the 6-minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO(2) who might be considered for cardiac transplantation. These data suggest that, although hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables.

Authors
Felker, GM; Whellan, D; Kraus, WE; Clare, R; Zannad, F; Donahue, M; Adams, K; McKelvie, R; Piña, IL; O'Connor, CM; HF-ACTION Investigators,
MLA Citation
Felker, GM, Whellan, D, Kraus, WE, Clare, R, Zannad, F, Donahue, M, Adams, K, McKelvie, R, Piña, IL, O'Connor, CM, and HF-ACTION Investigators, . "N-terminal pro-brain natriuretic peptide and exercise capacity in chronic heart failure: data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study." Am Heart J 158.4 Suppl (October 2009): S37-S44.
PMID
19782787
Source
pubmed
Published In
American Heart Journal
Volume
158
Issue
4 Suppl
Publish Date
2009
Start Page
S37
End Page
S44
DOI
10.1016/j.ahj.2009.07.011

Method for establishing authorship in a multicenter clinical trial.

With the emergence of large multicenter trials over the past 20 years, the numbers of investigators involved and publications resulting from each study have grown exponentially. An efficient, fair, and effective way to establish authorship on study-related manuscripts could diminish conflict among the investigators and help ensure robust and timely dissemination of study results. This article describes a process developed by the investigators in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial (ClinicalTrials.gov registration number: NCT00047437) to establish authorship of the manuscripts describing the baseline characteristics, study design, and trial outcomes in an equitable and transparent manner based on objective, quantifiable contributions to the study as a whole. The HF-ACTION investigators developed a scoring system that assigned points to investigators by using the criteria established for enrollment, adherence to the exercise program, data completion, committee service, and other trial efforts. The scoring system has been successfully implemented for baseline manuscripts and has allowed many investigators to participate in the HF-ACTION publication process.

Authors
Whellan, DJ; Ellis, SJ; Kraus, WE; Hawthorne, K; Piña, IL; Keteyian, SJ; Kitzman, DW; Cooper, L; Lee, K; O'Connor, CM
MLA Citation
Whellan, DJ, Ellis, SJ, Kraus, WE, Hawthorne, K, Piña, IL, Keteyian, SJ, Kitzman, DW, Cooper, L, Lee, K, and O'Connor, CM. "Method for establishing authorship in a multicenter clinical trial." Ann Intern Med 151.6 (September 15, 2009): 414-420.
PMID
19755366
Source
pubmed
Published In
Annals of internal medicine
Volume
151
Issue
6
Publish Date
2009
Start Page
414
End Page
420

Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi), a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23) and from 121 controls without evidence of coronary stenosis (CADi = 0). 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003). Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2) = 0.776, P<0.0001). The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.

Authors
Sinnaeve, PR; Donahue, MP; Grass, P; Seo, D; Vonderscher, J; Chibout, S-D; Kraus, WE; Sketch, M; Nelson, C; Ginsburg, GS; Goldschmidt-Clermont, PJ; Granger, CB
MLA Citation
Sinnaeve, PR, Donahue, MP, Grass, P, Seo, D, Vonderscher, J, Chibout, S-D, Kraus, WE, Sketch, M, Nelson, C, Ginsburg, GS, Goldschmidt-Clermont, PJ, and Granger, CB. "Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease. (Published online)" PLoS One 4.9 (September 14, 2009): e7037-.
PMID
19750006
Source
pubmed
Published In
PloS one
Volume
4
Issue
9
Publish Date
2009
Start Page
e7037
DOI
10.1371/journal.pone.0007037

Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women.

OBJECTIVE: To determine whether circulating metabolic intermediates are related to insulin resistance and beta-cell dysfunction in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: In 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry-based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates. RESULTS: The 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (S(I)) (R(2) = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R(2) = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R(2) = 0.39). Sex differences were found for metabolic predictors of S(I) and DI. CONCLUSIONS: In addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.

Authors
Huffman, KM; Shah, SH; Stevens, RD; Bain, JR; Muehlbauer, M; Slentz, CA; Tanner, CJ; Kuchibhatla, M; Houmard, JA; Newgard, CB; Kraus, WE
MLA Citation
Huffman, KM, Shah, SH, Stevens, RD, Bain, JR, Muehlbauer, M, Slentz, CA, Tanner, CJ, Kuchibhatla, M, Houmard, JA, Newgard, CB, and Kraus, WE. "Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women." Diabetes Care 32.9 (September 2009): 1678-1683.
PMID
19502541
Source
pubmed
Published In
Diabetes Care
Volume
32
Issue
9
Publish Date
2009
Start Page
1678
End Page
1683
DOI
10.2337/dc08-2075

Effects of exercise training amount on physical activity energy expenditure.

INTRODUCTION: We examined the effects of three exercise training interventions on total physical activity energy expenditure (PAEE) or nonexercise PAEE in a randomized controlled trial where sedentary, overweight, and obese men and women were assigned to inactive control, low-amount/moderate-intensity, low-amount/vigorous-intensity, or high-amount/vigorous-intensity aerobic exercise. METHODS: To measure PAEE, triaxial RT3 accelerometers were worn by subjects for 7 d at the beginning and end of an 8-month exercise intervention. In total, 50 subjects (control, n = 8; two low-amount groups, n = 28; high-amount group, n = 14) had usable PAEE data collected at both time points. RESULTS: At baseline, subjects had an average age of 53.2 yr, had a body mass index of 29.7 kg x m(-2), and a relative peak VO2 of 28.7 mL x kg(-1) x min(-1). There were no significant differences between groups at baseline. After the intervention, average change in total PAEE was 8.4 +/- 20.9 kJ x h(-1) for controls, 58.6 +/- 20.9 kJ x h(-1) for the two low-amount groups, and 138.1 +/- 33.5 kJ x h(-1) for the high-amount group (means +/- SE). The high-amount group experienced a significantly greater increase in total PAEE compared with the controls (P = 0.02). As expected, total PAEE increased with increasing exercise volume. Average change in nonexercise PAEE was 8.4 +/- 20.9 kJ x h(-1) for control, 25.1 +/- 20.9 kJ x h(-1) for the low-amount groups combined, and 62.8 +/- 29.3 kJ x h(-1) for the high-amount group. There was no statistically significant difference in change of nonexercise PAEE among groups. CONCLUSIONS: We conclude that in middle-aged overweight or obese subjects participating in an extended exercise intervention, total PAEE increased, and there was no compensatory decrease in nonexercise PAEE.

Authors
Hollowell, RP; Willis, LH; Slentz, CA; Topping, JD; Bhakpar, M; Kraus, WE
MLA Citation
Hollowell, RP, Willis, LH, Slentz, CA, Topping, JD, Bhakpar, M, and Kraus, WE. "Effects of exercise training amount on physical activity energy expenditure." Med Sci Sports Exerc 41.8 (August 2009): 1640-1644.
PMID
19568195
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
41
Issue
8
Publish Date
2009
Start Page
1640
End Page
1644
DOI
10.1249/MSS.0b013e31819c71a4

Development and Validation of a Peripheral Blood-Based Gene Expression Algorithm for the Detection of Coronary Artery Disease (CAD)

Authors
Wingrove, JA; Elashoff, M; Tingley, WG; Sehnert, AJ; Daniels, SE; Rosenberg, S; Kraus, WE; Newby, LK; Ginsburg, GS
MLA Citation
Wingrove, JA, Elashoff, M, Tingley, WG, Sehnert, AJ, Daniels, SE, Rosenberg, S, Kraus, WE, Newby, LK, and Ginsburg, GS. "Development and Validation of a Peripheral Blood-Based Gene Expression Algorithm for the Detection of Coronary Artery Disease (CAD)." ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 29.7 (July 2009): E24-E24.
Source
wos-lite
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
29
Issue
7
Publish Date
2009
Start Page
E24
End Page
E24

Comparing the 7-day physical activity recall with a triaxial accelerometer for measuring time in exercise.

PURPOSE: The primary study aim was to evaluate associations of estimated weekly minutes of moderate-to-vigorous-intensity exercise from self-reports of the telephone-administered 7-Day Physical Activity Recall (7-Day PAR) with data captured by the RT3 triaxial accelerometer. METHODS: This investigation was undertaken as part of the FRESH START study, a randomized clinical trial that tested an iteratively tailored diet and exercise mailed print intervention among newly diagnosed breast and prostate cancer survivors. A convenience sample of 139 medically eligible subjects living within a 60-mile radius of the study center provided both 7-Day PAR and accelerometer data at enrollment. Ultimately, substudy subjects (n = 115) were found eligible for the FRESH START study and randomized to one of two study treatment arms. Follow-up assessments at year 1 (n = 103) and year 2 (n = 99) provided both the 7-Day PAR and the accelerometer data. RESULTS: There was moderate agreement between the 7-Day PAR and the accelerometer with longitudinal serial correlation coefficients of 0.54 (baseline), 0.24 (year 1), and 0.53 (year 2), all P values <0.01, although the accelerometer estimates for weekly time in moderate-to-vigorous physical activity (PA) were much higher than those of the 7-Day PAR at all time points. The two methods were poorly correlated in assessing sensitivity to change from baseline to year 1 (rho = 0.11, P = 0.30). Using mixed models repeated-measures analysis, both methods exhibited similar nonsignificant treatment arm x time interaction P values (7-Day PAR = 0.22, accelerometer = 0.23). CONCLUSIONS: The correlations for three serial time points were in agreement with findings of other studies that compared self-reported time in exercise with PA captured by accelerometry. However, these methods capture somewhat different dimensions of PA and provide differing estimates of change over time.

Authors
Sloane, R; Snyder, DC; Demark-Wahnefried, W; Lobach, D; Kraus, WE
MLA Citation
Sloane, R, Snyder, DC, Demark-Wahnefried, W, Lobach, D, and Kraus, WE. "Comparing the 7-day physical activity recall with a triaxial accelerometer for measuring time in exercise." Med Sci Sports Exerc 41.6 (June 2009): 1334-1340.
PMID
19461530
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
41
Issue
6
Publish Date
2009
Start Page
1334
End Page
1340
DOI
10.1249/MSS.0b013e3181984fa8

Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial.

CONTEXT: Findings from previous studies of the effects of exercise training on patient-reported health status have been inconsistent. OBJECTIVE: To test the effects of exercise training on health status among patients with heart failure. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized controlled trial among 2331 medically stable outpatients with heart failure with left ventricular ejection fraction of 35% or less. Patients were randomized from April 2003 through February 2007. INTERVENTIONS: Usual care plus aerobic exercise training (n = 1172), consisting of 36 supervised sessions followed by home-based training, vs usual care alone (n = 1159). Randomization was stratified by heart failure etiology, which was a covariate in all models. MAIN OUTCOME MEASURES: Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scale and key subscales at baseline, every 3 months for 12 months, and annually thereafter for up to 4 years. The KCCQ is scored from 0 to 100 with higher scores corresponding to better health status. Treatment group effects were estimated using linear mixed models according to the intention-to-treat principle. RESULTS: Median follow-up was 2.5 years. At 3 months, usual care plus exercise training led to greater improvement in the KCCQ overall summary score (mean, 5.21; 95% confidence interval, 4.42 to 6.00) compared with usual care alone (3.28; 95% confidence interval, 2.48 to 4.09). The additional 1.93-point increase (95% confidence interval, 0.84 to 3.01) in the exercise training group was statistically significant (P < .001). After 3 months, there were no further significant changes in KCCQ score for either group (P = .85 for the difference between slopes), resulting in a sustained, greater improvement overall for the exercise group (P < .001). Results were similar on the KCCQ subscales, and no subgroup interactions were detected. CONCLUSIONS: Exercise training conferred modest but statistically significant improvements in self-reported health status compared with usual care without training. Improvements occurred early and persisted over time. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00047437.

Authors
Flynn, KE; Piña, IL; Whellan, DJ; Lin, L; Blumenthal, JA; Ellis, SJ; Fine, LJ; Howlett, JG; Keteyian, SJ; Kitzman, DW; Kraus, WE; Miller, NH; Schulman, KA; Spertus, JA; O'Connor, CM; Weinfurt, KP; HF-ACTION Investigators,
MLA Citation
Flynn, KE, Piña, IL, Whellan, DJ, Lin, L, Blumenthal, JA, Ellis, SJ, Fine, LJ, Howlett, JG, Keteyian, SJ, Kitzman, DW, Kraus, WE, Miller, NH, Schulman, KA, Spertus, JA, O'Connor, CM, Weinfurt, KP, and HF-ACTION Investigators, . "Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial." JAMA 301.14 (April 8, 2009): 1451-1459.
PMID
19351942
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
301
Issue
14
Publish Date
2009
Start Page
1451
End Page
1459
DOI
10.1001/jama.2009.457

Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.

CONTEXT: Guidelines recommend that exercise training be considered for medically stable outpatients with heart failure. Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes. OBJECTIVE: To test the efficacy and safety of exercise training among patients with heart failure. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized controlled trial of 2331 medically stable outpatients with heart failure and reduced ejection fraction. Participants in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France; median follow-up was 30 months. INTERVENTIONS: Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone. MAIN OUTCOME MEASURES: Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or heart failure hospitalization. RESULTS: The median age was 59 years, 28% were women, and 37% had New York Heart Association class III or IV symptoms. Heart failure etiology was ischemic in 51%, and median left ventricular ejection fraction was 25%. Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12. A total of 759 patients (65%) in the exercise training group died or were hospitalized compared with 796 patients (68%) in the usual care group (hazard ratio [HR], 0.93 [95% confidence interval {CI}, 0.84-1.02]; P = .13). There were nonsignificant reductions in the exercise training group for mortality (189 patients [16%] in the exercise training group vs 198 patients [17%] in the usual care group; HR, 0.96 [95% CI, 0.79-1.17]; P = .70), cardiovascular mortality or cardiovascular hospitalization (632 [55%] in the exercise training group vs 677 [58%] in the usual care group; HR, 0.92 [95% CI, 0.83-1.03]; P = .14), and cardiovascular mortality or heart failure hospitalization (344 [30%] in the exercise training group vs 393 [34%] in the usual care group; HR, 0.87 [95% CI, 0.75-1.00]; P = .06). In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics, the HRs were 0.89 (95% CI, 0.81-0.99; P = .03) for all-cause mortality or hospitalization, 0.91 (95% CI, 0.82-1.01; P = .09) for cardiovascular mortality or cardiovascular hospitalization, and 0.85 (95% CI, 0.74-0.99; P = .03) for cardiovascular mortality or heart failure hospitalization. Other adverse events were similar between the groups. CONCLUSIONS: In the protocol-specified primary analysis, exercise training resulted in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points. After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00047437.

Authors
O'Connor, CM; Whellan, DJ; Lee, KL; Keteyian, SJ; Cooper, LS; Ellis, SJ; Leifer, ES; Kraus, WE; Kitzman, DW; Blumenthal, JA; Rendall, DS; Miller, NH; Fleg, JL; Schulman, KA; McKelvie, RS; Zannad, F; Piña, IL; HF-ACTION Investigators,
MLA Citation
O'Connor, CM, Whellan, DJ, Lee, KL, Keteyian, SJ, Cooper, LS, Ellis, SJ, Leifer, ES, Kraus, WE, Kitzman, DW, Blumenthal, JA, Rendall, DS, Miller, NH, Fleg, JL, Schulman, KA, McKelvie, RS, Zannad, F, Piña, IL, and HF-ACTION Investigators, . "Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial." JAMA 301.14 (April 8, 2009): 1439-1450.
PMID
19351941
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
301
Issue
14
Publish Date
2009
Start Page
1439
End Page
1450
DOI
10.1001/jama.2009.454

A sex-specific relationship between capillary density and anaerobic threshold.

Although both capillary density and peak oxygen consumption (Vo(2)) improve with exercise training, it is difficult to find a relationship between these two measures. It has been suggested that peak Vo(2) may be more related to central hemodynamics than to the oxidative potential of skeletal muscle, which may account for this observation. We hypothesized that change in a measure of submaximal performance, anaerobic threshold, might be related to change in skeletal muscle capillary density, a marker of oxidative potential in muscle, with training. Due to baseline differences among these variables, we also hypothesized that relationships might be sex specific. A group of 21 subjects completed an inactive control period, whereas 28 subjects (17 men and 11 women) participated in a 6-mo high-intensity exercise program. All subjects were sedentary, overweight, and dyslipidemic. Potential relationships were assessed between change in capillary density with both change in Vo(2) at peak and at anaerobic threshold with exercise training. All variables and relationships were assessed for sex-specific effects. Change in peak Vo(2) was not related to change in capillary density after exercise training in either sex. Men had a positive correlation between change in Vo(2) at anaerobic threshold and change in capillary density with exercise training (r = 0.635; P < 0.01), whereas women had an inverse relationship (r = -0.636; P < 0.05) between the change in these variables. These findings suggest that, although enhanced capillary density is associated with training-induced improvements in submaximal performance in men, this relationship is different in women.

Authors
Robbins, JL; Duscha, BD; Bensimhon, DR; Wasserman, K; Hansen, JE; Houmard, JA; Annex, BH; Kraus, WE
MLA Citation
Robbins, JL, Duscha, BD, Bensimhon, DR, Wasserman, K, Hansen, JE, Houmard, JA, Annex, BH, and Kraus, WE. "A sex-specific relationship between capillary density and anaerobic threshold." J Appl Physiol (1985) 106.4 (April 2009): 1181-1186.
PMID
19164774
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
106
Issue
4
Publish Date
2009
Start Page
1181
End Page
1186
DOI
10.1152/japplphysiol.90947.2008

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation.

The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of approximately 12 miles/wk, 1,200 kcal/wk at 40-55% peak O(2) consumption (Vo(2peak)), 200 min exercise/wk], 2) low volume/vigorous intensity ( approximately 12 miles/wk, 1,200 kcal/wk at 65-80% Vo(2peak), 125 min/wk), and 3) high volume/vigorous intensity ( approximately 20 miles/wk, 2,000 kcal/wk at 65-80% Vo(2peak), 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, S(I)) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. S(I) increased with training compared with the sedentary condition (P < or = 0.05) at 16-24 h with all of the exercise prescriptions. S(I) decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days S(I) was significantly elevated compared with sedentary (P < or = 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.

Authors
Bajpeyi, S; Tanner, CJ; Slentz, CA; Duscha, BD; McCartney, JS; Hickner, RC; Kraus, WE; Houmard, JA
MLA Citation
Bajpeyi, S, Tanner, CJ, Slentz, CA, Duscha, BD, McCartney, JS, Hickner, RC, Kraus, WE, and Houmard, JA. "Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation." J Appl Physiol (1985) 106.4 (April 2009): 1079-1085.
PMID
19196913
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
106
Issue
4
Publish Date
2009
Start Page
1079
End Page
1085
DOI
10.1152/japplphysiol.91262.2008

A Multivariable Model From HF-ACTION Predicting Peak VO2 in a Heart Failure Population

Authors
Kraus, WE; Ellis, SJ; Fleg, JL; Keteyian, SJ; Pina, IL; Bensimhon, DR; Leifer, ES; Kittzman, DW; O'Connor, CM; Whellan, DJ; Investigators, HFACTION
MLA Citation
Kraus, WE, Ellis, SJ, Fleg, JL, Keteyian, SJ, Pina, IL, Bensimhon, DR, Leifer, ES, Kittzman, DW, O'Connor, CM, Whellan, DJ, and Investigators, HFACTION. "A Multivariable Model From HF-ACTION Predicting Peak VO2 in a Heart Failure Population." JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 53.10 (March 10, 2009): A301-A301.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
53
Issue
10
Publish Date
2009
Start Page
A301
End Page
A301

A Simple and Effective Approach to Improving Cardiac Rehabilitation (CR) Referrals: Improving Clinical Practice Through Mandatory Computerized Physician Order Entry (CPOE)

Authors
Patel, MJ; Bensimhon, DR; Granger, BB; Mendys, P; Craig, KP; Jr, MB; Kraus, WE; Heinsimer, JA
MLA Citation
Patel, MJ, Bensimhon, DR, Granger, BB, Mendys, P, Craig, KP, Jr, MB, Kraus, WE, and Heinsimer, JA. "A Simple and Effective Approach to Improving Cardiac Rehabilitation (CR) Referrals: Improving Clinical Practice Through Mandatory Computerized Physician Order Entry (CPOE)." JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 53.10 (March 10, 2009): A225-A225.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
53
Issue
10
Publish Date
2009
Start Page
A225
End Page
A225

Relationship Between NTproBNP and Exercise Capacity in Chronic Heart Failure: Baseline Data from the HF-ACTION Study

Authors
Felker, GM; Zannad, F; Donahue, M; Adams, KF; McKelvie, R; Claire, R; Kraus, WE; Whellan, D; Pina, I; O'Connor, CM
MLA Citation
Felker, GM, Zannad, F, Donahue, M, Adams, KF, McKelvie, R, Claire, R, Kraus, WE, Whellan, D, Pina, I, and O'Connor, CM. "Relationship Between NTproBNP and Exercise Capacity in Chronic Heart Failure: Baseline Data from the HF-ACTION Study." JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 53.10 (March 10, 2009): A189-A189.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
53
Issue
10
Publish Date
2009
Start Page
A189
End Page
A189

Genetic effects in the leukotriene biosynthesis pathway and association with atherosclerosis.

Leukotrienes are arachidonic acid derivatives long known for their inflammatory properties and their involvement with a number of human diseases, most particularly asthma. Recently, leukotriene-based inflammation has also been shown to play an important role in atherosclerosis: ALOX5AP and LTA4H, both genes in the leukotriene biosynthesis pathway, have individually been shown to be associated with various cardiovascular disease (CVD) phenotypes. To assess the role of the leukotriene pathway in CVD pathogenesis, we performed genetic association studies of ALOX5AP and LTA4H in a family based study of early onset coronary artery disease (EOCAD) (GENECARD, 1,101 families) and in a non-familial dataset of EOCAD (CATHGEN, 656 cases and 405 controls). We found weak to moderate association between single nucleotide polymorphisms (SNPs) in ALOX5AP and LTA4H with EOCAD. The previously reported four-SNP haplotype (HapA) in ALOX5AP showed association with EOCAD in CATHGEN (P = 0.02), while controlling for age, race and CVD risk factors. HapK, the previously reported ten-SNP haplotype in LTA4H was associated with EOCAD in CATHGEN (P = 0.04). Another previously reported four-SNP haplotype in ALOX5AP (HapB) was not significant in our sample (P = 0.39). The overall lack of (or weak) association of single SNPs as compared with the haplotype results demonstrates the need for analyzing multiple SNPs within each gene in such studies. Interestingly, we detected an association of SNPs in ALOX5 (P < 0.05), the target of ALOX5AP, with CVD. Using a pathway-based approach, we also detected statistical evidence for interactions among ALOX5, ALOX5AP and LTA4H using RNA expression data from a collection of freshly harvested human aortas with varying degrees of atherosclerosis. The GENECARD families did not demonstrate evidence for linkage or association with ALOX5, ALOX5AP or LTA4H. Our results support a modest role for the leukotriene pathway in atherosclerosis pathogenesis, reveal important genomic interactions within the pathway, and suggest the importance of using pathway-based modeling for evaluating the genomics of atherosclerosis susceptibility.

Authors
Crosslin, DR; Shah, SH; Nelson, SC; Haynes, CS; Connelly, JJ; Gadson, S; Goldschmidt-Clermont, PJ; Vance, JM; Rose, J; Granger, CB; Seo, D; Gregory, SG; Kraus, WE; Hauser, ER
MLA Citation
Crosslin, DR, Shah, SH, Nelson, SC, Haynes, CS, Connelly, JJ, Gadson, S, Goldschmidt-Clermont, PJ, Vance, JM, Rose, J, Granger, CB, Seo, D, Gregory, SG, Kraus, WE, and Hauser, ER. "Genetic effects in the leukotriene biosynthesis pathway and association with atherosclerosis." Hum Genet 125.2 (March 2009): 217-229.
PMID
19130089
Source
pubmed
Published In
Human Genetics
Volume
125
Issue
2
Publish Date
2009
Start Page
217
End Page
229
DOI
10.1007/s00439-008-0619-0

Effects of exercise on lipoprotein particles in women with polycystic ovary syndrome.

PURPOSE: Women with polycystic ovary syndrome (PCOS) commonly have insulin resistance. Insulin resistance is associated with marked abnormalities of lipoprotein size and subclass particle concentration. The purpose of this study was to examine the effects of a moderate-intensity exercise program without weight loss on lipoprotein profiles in women with PCOS. METHODS: Thirty-seven sedentary PCOS women were randomized to either an 8- to 12-wk ramp-up followed by a 12-wk moderate-intensity exercise program (16-24 wk total, approximately 228 min x wk at 40-60% peak V x O2, n = 21) or control (no change in lifestyle, n = 16). PCOS was defined as or=8). Fasting lipoprotein profiles were obtained before and after the intervention. Nuclear magnetic resonance spectroscopy was used to quantify the following: average particle size, total and subclass concentrations of HDL, LDL, and VLDL particles, and calculated HDL cholesterol, triglycerides, and VLDL triglycerides. Wilcoxon exact rank sums tests were used to compare changes in these parameters in the exercise group relative to controls. RESULTS: Twenty women (8 exercisers, 12 controls) completed the study. Comparing exercisers to controls, significant changes were seen in concentrations of the following lipoprotein parameters that are associated with decreased insulin resistance: decreased large VLDL (P = 0.007), calculated triglycerides (P = 0.003), VLDL triglycerides (P = 0.003), and medium/small HDL (P = 0.031) and increased large HDL (P = 0.002) and average HDL size (P = 0.001). CONCLUSIONS: In this trial, moderate-intensity exercise without significant weight loss improved several components of the lipoprotein profiles of women with PCOS. These findings support the beneficial role of moderate exercise in this high-risk population.

Authors
Brown, AJ; Setji, TL; Sanders, LL; Lowry, KP; Otvos, JD; Kraus, WE; Svetkey, PL
MLA Citation
Brown, AJ, Setji, TL, Sanders, LL, Lowry, KP, Otvos, JD, Kraus, WE, and Svetkey, PL. "Effects of exercise on lipoprotein particles in women with polycystic ovary syndrome." Med Sci Sports Exerc 41.3 (March 2009): 497-504.
PMID
19204602
Source
pubmed
Published In
Medicine and Science in Sports and Exercise
Volume
41
Issue
3
Publish Date
2009
Start Page
497
End Page
504
DOI
10.1249/MSS.0b013e31818c6c0c

Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise.

Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigate the hypothesis that exercise-mediated adaptations in mRNA levels differ between women and men. The mRNA abundance of representative lipogenic and lipolytic genes from major lipid metabolism pathways, as well as representative lipogenic and lipolytic transcription factors, were determined by real-time PCR from skeletal muscle biopsies collected before and approximately 24 h after the final bout of 6 mo of EE. Six months of EE led to increases in muscle lipoprotein lipase, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, carnitine palmitoyltransferase-1 beta, diacylglycerol acyltransferase-1, and acid ceramidase mRNA in women, but not men. In contrast, in men, EE led to reductions in the mRNA content of the lipogenic factors sterol regulatory element binding protein-1c and serine palmitoyl transferase. These data suggest that EE-mediated alterations in the abundance of the lipid metabolism genes studied here are fundamentally different between overweight and obese middle-aged women and men. Future studies should determine whether these adaptations in mRNA levels translate into changes in protein function.

Authors
Smith, IJ; Huffman, KM; Durheim, MT; Duscha, BD; Kraus, WE
MLA Citation
Smith, IJ, Huffman, KM, Durheim, MT, Duscha, BD, and Kraus, WE. "Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise." Physiol Genomics 36.3 (February 2, 2009): 149-157.
PMID
19033545
Source
pubmed
Published In
Physiological genomics
Volume
36
Issue
3
Publish Date
2009
Start Page
149
End Page
157
DOI
10.1152/physiolgenomics.90216.2008

Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families), we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004) in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72), family-based association of this block with CAD (p = 0.02), and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a) 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05), showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09); and (b) GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02). A promoter SNP (rs16147) within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04). To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03). Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects) and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

Authors
Shah, SH; Freedman, NJ; Zhang, L; Crosslin, DR; Stone, DH; Haynes, C; Johnson, J; Nelson, S; Wang, L; Connelly, JJ; Muehlbauer, M; Ginsburg, GS; Crossman, DC; Jones, CJH; Vance, J; Sketch, MH; Granger, CB; Newgard, CB; Gregory, SG; Goldschmidt-Clermont, PJ; Kraus, WE; Hauser, ER
MLA Citation
Shah, SH, Freedman, NJ, Zhang, L, Crosslin, DR, Stone, DH, Haynes, C, Johnson, J, Nelson, S, Wang, L, Connelly, JJ, Muehlbauer, M, Ginsburg, GS, Crossman, DC, Jones, CJH, Vance, J, Sketch, MH, Granger, CB, Newgard, CB, Gregory, SG, Goldschmidt-Clermont, PJ, Kraus, WE, and Hauser, ER. "Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis." PLoS Genet 5.1 (January 2009): e1000318-.
PMID
19119412
Source
pubmed
Published In
PLoS genetics
Volume
5
Issue
1
Publish Date
2009
Start Page
e1000318
DOI
10.1371/journal.pgen.1000318

High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.

Integration of genetic and metabolic profiling holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolomic profiles has not been evaluated in humans. We performed quantitative mass spectrometry-based metabolic profiling in 117 individuals within eight multiplex families from the GENECARD study of premature CAD. Heritabilities were calculated using variance components. We found high heritabilities for amino acids (arginine, ornithine, alanine, proline, leucine/isoleucine, valine, glutamate/glutamine, phenylalanine and glycine; h(2)=0.33-0.80, P=0.005-1.9 x 10(-16)), free fatty acids (arachidonic, palmitic, linoleic; h(2)=0.48-0.59, P=0.002-0.00005) and acylcarnitines (h(2)=0.23-0.79, P=0.05-0.0000002). Principal components analysis was used to identify metabolite clusters. Reflecting individual metabolites, several components were heritable, including components comprised of ketones, beta-hydroxybutyrate and C2-acylcarnitine (h(2)=0.61); short- and medium-chain acylcarnitines (h(2)=0.39); amino acids (h(2)=0.44); long-chain acylcarnitines (h(2)=0.39) and branched-chain amino acids (h(2)=0.27). We report a novel finding of high heritabilities of metabolites in premature CAD, establishing a possible genetic basis for these profiles. These results have implications for understanding CAD pathophysiology and genetics.

Authors
Shah, SH; Hauser, ER; Bain, JR; Muehlbauer, MJ; Haynes, C; Stevens, RD; Wenner, BR; Dowdy, ZE; Granger, CB; Ginsburg, GS; Newgard, CB; Kraus, WE
MLA Citation
Shah, SH, Hauser, ER, Bain, JR, Muehlbauer, MJ, Haynes, C, Stevens, RD, Wenner, BR, Dowdy, ZE, Granger, CB, Ginsburg, GS, Newgard, CB, and Kraus, WE. "High heritability of metabolomic profiles in families burdened with premature cardiovascular disease." Mol Syst Biol 5 (2009): 258-.
PMID
19357637
Source
pubmed
Published In
Molecular systems biology
Volume
5
Publish Date
2009
Start Page
258
DOI
10.1038/msb.2009.11

Relationship of age and exercise performance in patients with heart failure: The HF-ACTION study

Background: More than three fourths of patients with heart failure (HF) are 65 years and older, and older age is associated with worse symptoms and prognoses than is younger age. Reduced exercise capacity is a chief HF complaint and indicates poorer prognosis, especially among elderly persons, but the mechanisms underlying functional decline in older patients with HF are largely unknown. Methods: Baseline cardiopulmonary exercise testing data from the HF-ACTION trial were assessed to clarify age effects on peak oxygen consumption (VO2) and ventilation-carbon dioxide production (VE/VCO2) slope. Results: Among 2,331 New York Heart Association class II-IV patients with HF, increased age corresponded to decreased peak VO2 (-0.14 mL kg-1 min-1 per year >40 years; P < .0001) and increased VE/VCO2 slope (0.30 U/y >70 years; P < .0001). In a multivariable model with 34 other potential determinants, age was the strongest independent predictor of peak VO2 (partial R2 0.130, total R2 0.392; P < .001) and a significant but relatively weaker predictor of VE/VCO2 slope (partial R2 0.037, total R2 0.199; P < .001). Blunted peak heart rate was also a strong predictor of peak VO2. Although peak heart rate and age were strongly correlated, both were significant independent predictors of peak VO2 when analyzed simultaneously in a model. Aggregate comorbidity increased significantly with age but did not account for age effects on peak VO2. Conclusions: Age is the strongest predictor of peak VO2 and a significant predictor of VE/VCO2 slope in the HF-ACTION population. Age-dependent comorbidities do not explain changes in peak VO2. Age-related changes in cardiovascular physiology, potentially magnified by the HF disease state, should be considered a contributor to the pathophysiology and a target for more effective therapy in older patients with HF. © 2009 Mosby, Inc.

Authors
Forman, DE; Clare, R; Kitzman, DW; Ellis, SJ; Fleg, JL; Chiara, T; Fletcher, G; Kraus, WE
MLA Citation
Forman, DE, Clare, R, Kitzman, DW, Ellis, SJ, Fleg, JL, Chiara, T, Fletcher, G, and Kraus, WE. "Relationship of age and exercise performance in patients with heart failure: The HF-ACTION study." American Heart Journal 158.4 SUPPL. (2009): S6-S15.
PMID
19782790
Source
scival
Published In
American Heart Journal
Volume
158
Issue
4 SUPPL.
Publish Date
2009
Start Page
S6
End Page
S15
DOI
10.1016/j.ahj.2009.07.018

Safety of symptom-limited cardiopulmonary exercise testing in patients with chronic heart failure due to severe left ventricular systolic dysfunction

Background: To assess the safety of symptom-limited exercise testing in patients with New York Heart Association class II-IV heart failure symptoms due to left ventricular systolic dysfunction, we investigated the frequency of all-cause fatal and nonfatal major cardiovascular (CV) events among subjects enrolled in a prospective clinical trial (HF-ACTION). We hypothesized that exercise testing would be safe, as defined by a rate for all-cause death of <0.1 per 1,000 tests and a rate of nonfatal CV events <1.0 per 1,000 tests. Methods: Before enrollment and at 3, 12, and 24 months after randomization, subjects were scheduled to complete a symptom-limited graded exercise test with open-circuit spirometry for analysis of expired gases. To ensure the accurate reporting of exercise test-related events, we report deaths and nonfatal major CV events per 1,000 tests at months 3, 12, or 24 after randomization. Results: A total of 2,331 subjects were randomized into HF-ACTION. After randomization, 2,037 subjects completed 4,411 exercise tests. There were no test-related deaths, exacerbation of heart failure or angina requiring hospitalization, myocardial infarctions, strokes, or transient ischemic attacks. There was one episode each of ventricular fibrillation and sustained ventricular tachycardia. There were no exercise test-related implantable cardioverter defibrillator discharges requiring hospitalization. These findings correspond to zero deaths per 1,000 exercise tests and 0.45 nonfatal major CV events per 1,000 exercise tests (95% CI 0.11-1.81). Conclusions: In New York Heart Association class II-IV patients with severe left ventricular systolic dysfunction, we observed that symptom-limited exercise testing is safe based on no deaths and a rate of nonfatal major CV events that is <0.5 per 1,000 tests. © 2009 Mosby, Inc.

Authors
Keteyian, SJ; Isaac, D; Thadani, U; Roy, BA; Bensimhon, DR; McKelvie, R; Russell, SD; Hellkamp, AS; Kraus, WE
MLA Citation
Keteyian, SJ, Isaac, D, Thadani, U, Roy, BA, Bensimhon, DR, McKelvie, R, Russell, SD, Hellkamp, AS, and Kraus, WE. "Safety of symptom-limited cardiopulmonary exercise testing in patients with chronic heart failure due to severe left ventricular systolic dysfunction." American Heart Journal 158.4 SUPPL. (2009): S72-S77.
PMID
19782792
Source
scival
Published In
American Heart Journal
Volume
158
Issue
4 SUPPL.
Publish Date
2009
Start Page
S72
End Page
S77
DOI
10.1016/j.ahj.2009.07.014

Recommendations for clinical exercise laboratories: A scientific statement from the american heart association

Authors
Myers, J; Arena, R; Franklin, B; Pina, I; Kraus, WE; McInnis, K; Balady, GJ
MLA Citation
Myers, J, Arena, R, Franklin, B, Pina, I, Kraus, WE, McInnis, K, and Balady, GJ. "Recommendations for clinical exercise laboratories: A scientific statement from the american heart association." Circulation 119.24 (2009): 3144-3161.
PMID
19487589
Source
scival
Published In
Circulation
Volume
119
Issue
24
Publish Date
2009
Start Page
3144
End Page
3161
DOI
10.1161/CIRCULATIONAHA.109.192520

Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study.

BACKGROUND: A feasibility study examining the effects of supervised aerobic exercise training on cardiopulmonary and quality of life (QOL) endpoints among postsurgical nonsmall cell lung cancer (NSCLC) patients was conducted. METHODS: Using a single-group design, 20 patients with stage I-IIIB NSCLC performed 3 aerobic cycle ergometry sessions per week at 60% to 100% of peak workload for 14 weeks. Peak oxygen consumption (VO(2peak)) was assessed using an incremental exercise test. QOL and fatigue were assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale. RESULTS: Nineteen patients completed the study. Intention-to-treat analysis indicated that VO(2peak) increased 1.1 mL/kg(-1)/min(-1) (95% confidence interval [CI], -0.3-2.5; P = .109) and peak workload increased 9 W (95% CI, 3-14; P = .003), whereas FACT-L increased 10 points (95% CI, -1-22; P = .071) and fatigue decreased 7 points (95% CI; -1 to -17; P = .029) from baseline to postintervention. Per protocol analyses indicated greater improvements in cardiopulmonary and QOL endpoints among patients not receiving adjuvant chemotherapy. CONCLUSIONS: This pilot study provided proof of principle that supervised aerobic training is safe and feasible for postsurgical NSCLC patients. Aerobic exercise training is also associated with significant improvements in QOL and select cardiopulmonary endpoints, particularly among patients not receiving chemotherapy. Larger randomized trials are warranted.

Authors
Jones, LW; Eves, ND; Peterson, BL; Garst, J; Crawford, J; West, MJ; Mabe, S; Harpole, D; Kraus, WE; Douglas, PS
MLA Citation
Jones, LW, Eves, ND, Peterson, BL, Garst, J, Crawford, J, West, MJ, Mabe, S, Harpole, D, Kraus, WE, and Douglas, PS. "Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study." Cancer 113.12 (December 15, 2008): 3430-3439.
PMID
18988290
Source
pubmed
Published In
Cancer
Volume
113
Issue
12
Publish Date
2008
Start Page
3430
End Page
3439
DOI
10.1002/cncr.23967

ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.

BACKGROUND: Use of drug-eluting stents (DES) has reduced in-stent restenosis after percutaneous coronary intervention (PCI); however, DES are associated with late stent thrombosis. There is no accurate way to predict in-stent restenosis, although risk factors for atherosclerosis overlap those for in-stent restenosis. Therefore, we evaluated atherosclerosis candidate genes for association with in-stent restenosis. METHODS: We identified 46 consecutive cases that had undergone PCI with bare-metal stents who subsequently developed symptomatic in-stent restenosis of the target lesion (>/=75% luminal narrowing) within 6 months. Forty-six age-, race-, vessel-diameter- and sex-matched controls without in-stent restenosis after PCI with bare-metal stent were also identified. Single-nucleotide polymorphisms (SNPs, N=82) from 39 candidate atherosclerosis genes were genotyped. Multivariable logistic regression models were used to test for association. RESULTS: Five SNPs were associated with in-stent restenosis. Three ALOX5AP SNPs were most strongly associated, two with increased risk (OR 3.74, p=0.01; OR 3.46, p=0.02), and the third with decreased risk of in-stent restenosis (OR 0.09, p=0.004). Two ALOX5AP haplotypes were associated with in-stent restenosis (HapB: OR 3.13, p=0.03); and a haplotype similar to HapA: OR 0.14, p=0.0009). CONCLUSIONS: ALOX5AP, a gene within the inflammatory leukotriene pathway linked to and associated with coronary atherosclerosis, is also associated with in-stent restenosis. Genotyping these variants may help identify those at risk for in-stent restenosis who would benefit most from use of DES.

Authors
Shah, SH; Hauser, ER; Crosslin, D; Wang, L; Haynes, C; Connelly, J; Nelson, S; Johnson, J; Gadson, S; Nelson, CL; Seo, D; Gregory, S; Kraus, WE; Granger, CB; Goldschmidt-Clermont, P; Newby, LK
MLA Citation
Shah, SH, Hauser, ER, Crosslin, D, Wang, L, Haynes, C, Connelly, J, Nelson, S, Johnson, J, Gadson, S, Nelson, CL, Seo, D, Gregory, S, Kraus, WE, Granger, CB, Goldschmidt-Clermont, P, and Newby, LK. "ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention." Atherosclerosis 201.1 (November 2008): 148-154.
PMID
18374923
Source
pubmed
Published In
Atherosclerosis
Volume
201
Issue
1
Publish Date
2008
Start Page
148
End Page
154
DOI
10.1016/j.atherosclerosis.2008.01.011

Cancer survivors' health worries and associations with lifestyle practices.

This study examined among recently diagnosed breast and prostate cancer survivors (N = 678) associations between worry about a future diagnosis of heart disease or cancer and hypothetical and actual adherence to exercise and dietary guidelines. Greater worry about future illness was reported under the hypothetical scenario of nonadherence to guidelines relative to the scenario of adherence. Worry about potential heart disease was associated with actual adherence to guidelines, whereas worry about a potential cancer diagnosis was not. Findings suggest that the motivational properties of worry should be considered when developing interventions to reduce heart disease risk among cancer survivors.

Authors
Mosher, CE; Lipkus, IM; Sloane, R; Kraus, WE; Snyder, DC; Peterson, B; Jones, LW; Demark-Wahnefried, W
MLA Citation
Mosher, CE, Lipkus, IM, Sloane, R, Kraus, WE, Snyder, DC, Peterson, B, Jones, LW, and Demark-Wahnefried, W. "Cancer survivors' health worries and associations with lifestyle practices." J Health Psychol 13.8 (November 2008): 1105-1112.
PMID
18987083
Source
pubmed
Published In
Journal of Health Psychology
Volume
13
Issue
8
Publish Date
2008
Start Page
1105
End Page
1112
DOI
10.1177/1359105308095964

Discovery of Genes Expressed in Whole Blood which Identity Patients with Coronary Artery Disease

Authors
Wingrove, JA; Elashoff, M; Tingley, WG; Sehnert, AJ; Daniels, SE; Paoni, NF; Rosenberg, S; Kraus, WE; Newby, LK; Ginsburg, GS
MLA Citation
Wingrove, JA, Elashoff, M, Tingley, WG, Sehnert, AJ, Daniels, SE, Paoni, NF, Rosenberg, S, Kraus, WE, Newby, LK, and Ginsburg, GS. "Discovery of Genes Expressed in Whole Blood which Identity Patients with Coronary Artery Disease." CIRCULATION 118.18 (October 28, 2008): S389-S389.
Source
wos-lite
Published In
Circulation
Volume
118
Issue
18
Publish Date
2008
Start Page
S389
End Page
S389

Biliverdin Reductase Genetic Polymorphisms are Associated with Early-Onset Coronary Artery Disease In Two Datasets

Authors
Goswami, R; Sutton, BS; Rouf, C; Nelson, S; Haynes, C; Johnson, J; Goldschmidt-Clermont, P; Seo, D; Kraus, WE; Hauser, ER; Gregory, SG; Shah, SS
MLA Citation
Goswami, R, Sutton, BS, Rouf, C, Nelson, S, Haynes, C, Johnson, J, Goldschmidt-Clermont, P, Seo, D, Kraus, WE, Hauser, ER, Gregory, SG, and Shah, SS. "Biliverdin Reductase Genetic Polymorphisms are Associated with Early-Onset Coronary Artery Disease In Two Datasets." CIRCULATION 118.18 (October 28, 2008): S389-S390.
Source
wos-lite
Published In
Circulation
Volume
118
Issue
18
Publish Date
2008
Start Page
S389
End Page
S390

Gene Expression in Peripheral Blood Reflects the Presence and Extent of Coronary Artery Stenosis

Authors
Tingley, WG; Wingrove, JA; Sehnert, AJ; Elashoff, M; Daniels, SE; Rosenberg, S; Buellesfeld, L; Grube, E; Newby, LK; Ginsburg, GS; Kraus, WE
MLA Citation
Tingley, WG, Wingrove, JA, Sehnert, AJ, Elashoff, M, Daniels, SE, Rosenberg, S, Buellesfeld, L, Grube, E, Newby, LK, Ginsburg, GS, and Kraus, WE. "Gene Expression in Peripheral Blood Reflects the Presence and Extent of Coronary Artery Stenosis." October 12, 2008.
Source
wos-lite
Published In
The American Journal of Cardiology
Volume
102
Issue
8A
Publish Date
2008
Start Page
55I
End Page
55I

Change in self-efficacy partially mediates the effects of the FRESH START intervention on cancer survivors' dietary outcomes.

OBJECTIVE: This study examined change in self-efficacy as a mediator of the effects of a mailed print intervention on the dietary and exercise practices of newly diagnosed breast and prostate cancer survivors. METHOD: A total of 543 breast and prostate cancer patients were recruited from 39 states and two provinces within North America. Participants were randomly assigned to receive a 10-month program of tailored mailed print materials that aimed to increase fruit and vegetable consumption, reduce fat intake, and/or increase exercise or a 10-month program of publically available materials on diet and exercise. Telephone surveys conducted at baseline and 1 year assessed dietary practices, physical activity, and self-efficacy for engaging in these health behaviors. RESULTS: Results indicated that changes in self-efficacy for fat restriction and eating more fruits and vegetables were significant mediators of the intervention's effects on dietary outcomes at 1-year follow-up. The intervention did not significantly affect self-efficacy for exercise; however, a significant, positive relationship was found between self-efficacy for exercise and exercise duration at follow-up. CONCLUSIONS: Findings are largely consistent with Social Cognitive Theory and support the use of strategies to increase self-efficacy in health promotion interventions for cancer survivors.

Authors
Mosher, CE; Fuemmeler, BF; Sloane, R; Kraus, WE; Lobach, DF; Snyder, DC; Demark-Wahnefried, W
MLA Citation
Mosher, CE, Fuemmeler, BF, Sloane, R, Kraus, WE, Lobach, DF, Snyder, DC, and Demark-Wahnefried, W. "Change in self-efficacy partially mediates the effects of the FRESH START intervention on cancer survivors' dietary outcomes." Psychooncology 17.10 (October 2008): 1014-1023.
PMID
18300337
Source
pubmed
Published In
Psycho-Oncology
Volume
17
Issue
10
Publish Date
2008
Start Page
1014
End Page
1023
DOI
10.1002/pon.1327

Reproducibility of peak oxygen uptake and other cardiopulmonary exercise testing parameters in patients with heart failure (from the Heart Failure and A Controlled Trial Investigating Outcomes of exercise traiNing).

Peak oxygen uptake (pVo2) is an important parameter in assessing the functional capacity and prognosis of patients with heart failure. In heart failure trials, change in pVo2 was often used to assess the effectiveness of an intervention. However, the within-subject variability of pVo2 on serial testing may limit its usefulness. This study was designed to evaluate the within-subject variability of pVo2 over 2 baseline cardiopulmonary exercise tests. As a substudy of the HF-ACTION trial, 398 subjects (73% men, 27% women; mean age 59 years) with heart failure and left ventricular ejection fraction < or =35% underwent 2 baseline cardiopulmonary exercise tests within 14 days. Mean pVo2 was unchanged from test 1 to test 2 (15.16 +/- 4.97 vs 15.18 +/- 4.97 ml/kg/min; p = 0.78). However, mean within-subject absolute change was 1.3 ml/kg/min (10th, 90th percentiles 0.1, 3.0), with 46% of subjects increasing and 48% decreasing on the second test. Other parameters, including the ventilation-to-carbon-dioxide production slope and Vo2 at ventilatory threshold, also showed significant within-subject variation with minimal mean differences between tests. In conclusion, pVo2 showed substantial within-subject variability in patients with heart failure and should be taken into account in clinical applications. However, on repeated baseline cardiopulmonary exercise tests, there appears to be no familiarization effect for Vo2 in patients with HF. Therefore, in multicenter trials, there is no need to perform >1 baseline cardiopulmonary exercise test.

Authors
Bensimhon, DR; Leifer, ES; Ellis, SJ; Fleg, JL; Keteyian, SJ; Piña, IL; Kitzman, DW; McKelvie, RS; Kraus, WE; Forman, DE; Kao, AJ; Whellan, DJ; O'Connor, CM; Russell, SD; HF-ACTION Trial Investigators,
MLA Citation
Bensimhon, DR, Leifer, ES, Ellis, SJ, Fleg, JL, Keteyian, SJ, Piña, IL, Kitzman, DW, McKelvie, RS, Kraus, WE, Forman, DE, Kao, AJ, Whellan, DJ, O'Connor, CM, Russell, SD, and HF-ACTION Trial Investigators, . "Reproducibility of peak oxygen uptake and other cardiopulmonary exercise testing parameters in patients with heart failure (from the Heart Failure and A Controlled Trial Investigating Outcomes of exercise traiNing)." Am J Cardiol 102.6 (September 15, 2008): 712-717.
PMID
18773994
Source
pubmed
Published In
The American Journal of Cardiology
Volume
102
Issue
6
Publish Date
2008
Start Page
712
End Page
717
DOI
10.1016/j.amjcard.2008.04.047

Relationships between exercise-induced reductions in thigh intermuscular adipose tissue, changes in lipoprotein particle size, and visceral adiposity.

Small LDL and HDL particle size are characteristic of a proatherogenic lipoprotein profile. Aerobic exercise increases these particle sizes. Although visceral adipose tissue (VAT) has been strongly linked with dyslipidemia, the importance of intermuscular adipose tissue (IMAT) to dyslipidemia and exercise responses is less well understood. We measured exercise-associated changes in thigh IMAT and VAT and examined their relationships with changes in LDL and HDL particle size. Sedentary, dyslipidemic, overweight subjects (n = 73) completed 8-9 mo of aerobic training. Linear regression models were used to compare the power of IMAT change and VAT change to predict lipoprotein size changes. In men alone (n = 40), IMAT change correlated inversely with both HDL size change (r = -0.42, P = 0.007) and LDL size change (r = -0.52, P < 0.001). That is, reduction of IMAT was associated with a shift toward larger, less atherogenic lipoprotein particles. No significant correlations were observed in women. After adding VAT change to the model, IMAT change was the only significant predictor of either HDL size change (P = 0.034 for IMAT vs. 0.162 for VAT) or LDL size change (P = 0.004 for IMAT vs. 0.189 for VAT) in men. In conclusion, in overweight dyslipidemic men, exercise-associated change in thigh IMAT was inversely correlated with both HDL and LDL size change and was more predictive of these lipoprotein changes than was change in VAT. Reducing IMAT through aerobic exercise may be functionally related to some improvements in atherogenic dyslipidemia in men.

Authors
Durheim, MT; Slentz, CA; Bateman, LA; Mabe, SK; Kraus, WE
MLA Citation
Durheim, MT, Slentz, CA, Bateman, LA, Mabe, SK, and Kraus, WE. "Relationships between exercise-induced reductions in thigh intermuscular adipose tissue, changes in lipoprotein particle size, and visceral adiposity." Am J Physiol Endocrinol Metab 295.2 (August 2008): E407-E412.
PMID
18544640
Source
pubmed
Published In
American journal of physiology. Endocrinology and metabolism
Volume
295
Issue
2
Publish Date
2008
Start Page
E407
End Page
E412
DOI
10.1152/ajpendo.90397.2008

Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults.

Exercise training (ET) and hormone replacement therapy (HRT) are both recognized influences on insulin action, but the influence of HRT on responses to ET has not been examined. To determine if HRT use provided additive benefits for the response of insulin action to ET, we evaluated the impact of HRT use on changes in insulin during the course of a randomized, controlled, aerobic ET intervention. Subjects at baseline were sedentary, dyslipidemic, and overweight. These individuals were randomized to 6 months of one of 3 aerobic ET interventions or continued physical inactivity. In 206 subjects, an insulin sensitivity index (S(I)) was obtained with a frequently sampled intravenous glucose tolerance test pre- and post-ET. Baseline and postintervention fitness, regional adiposity, general adiposity, skeletal muscle biochemistry and histology, and serum lipoproteins were measured as other putative mediators influencing insulin action. Two-way analyses of variance were used to determine if sex or HRT use influenced responses to exercise training. Linear modeling was used to determine if predictors for response in S(I) differed by sex or HRT use(.) Women who used HRT (HRT+) demonstrated significantly greater improvements in S(I) with ET than women not using HRT (HRT-). In those HRT+ women, plasma triglyceride change best correlated with change in S(I). For HRT- women, capillary density change and, for men, subcutaneous adiposity change best correlated with change in S(I). In summary, in an ET intervention, HRT use appears to be associated with more robust responses in insulin action. Furthermore, relationships between ET-induced changes in insulin action and potential mediators of change in insulin action are different for men, and for women on or off HRT. These findings have implications for the relative utility of ET for improving insulin action in middle-aged men and women, particularly in the setting of differences in HRT use.

Authors
Huffman, KM; Slentz, CA; Johnson, JL; Samsa, GP; Duscha, BD; Tanner, CJ; Annex, BH; Houmard, JA; Kraus, WE
MLA Citation
Huffman, KM, Slentz, CA, Johnson, JL, Samsa, GP, Duscha, BD, Tanner, CJ, Annex, BH, Houmard, JA, and Kraus, WE. "Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults." Metabolism 57.7 (July 2008): 888-895.
PMID
18555828
Source
pubmed
Published In
Metabolism
Volume
57
Issue
7
Publish Date
2008
Start Page
888
End Page
895
DOI
10.1016/j.metabol.2008.01.034

Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease.

Previous association mapping on chromosome 3q13-21 detected evidence for association at the limbic system-associated membrane protein (LSAMP) gene in individuals with late-onset coronary artery disease (CAD). LSAMP has never been implicated in the pathogenesis of CAD. We sought to thoroughly characterize the association and the gene. Non-redundant single nucleotide polymorphisms (SNPs) across the gene were examined in an initial dataset (168 cases with late-onset CAD, 149 controls). Stratification analysis on left main CAD (N = 102) revealed stronger association, which was further validated in a validation dataset (141 cases with left main CAD, 215 controls), a third control dataset (N = 255), and a family-based dataset (N = 2954). A haplotype residing in a novel alternative transcript of the LSAMP gene was significant in all independent case-control datasets (p = 0.0001 to 0.0205) and highly significant in the joint analysis (p = 0.00004). Lower expression of the novel alternative transcript was associated with the risk haplotype (p = 0.0002) and atherosclerosis burden in human aortas (p = 0.0001). Furthermore, silencing LSAMP expression in human aortic smooth muscle cells (SMCs) substantially augmented SMC proliferation (p<0.01). Therefore, the risk conferred by the LSAMP haplotype appears to be mediated by LSAMP down-regulation, which may promote SMC proliferation in the arterial wall and progression of atherosclerosis.

Authors
Wang, L; Hauser, ER; Shah, SH; Seo, D; Sivashanmugam, P; Exum, ST; Gregory, SG; Granger, CB; Haines, JL; Jones, CJH; Crossman, D; Haynes, C; Kraus, WE; Freedman, NJ; Pericak-Vance, MA; Goldschmidt-Clermont, PJ; Vance, JM
MLA Citation
Wang, L, Hauser, ER, Shah, SH, Seo, D, Sivashanmugam, P, Exum, ST, Gregory, SG, Granger, CB, Haines, JL, Jones, CJH, Crossman, D, Haynes, C, Kraus, WE, Freedman, NJ, Pericak-Vance, MA, Goldschmidt-Clermont, PJ, and Vance, JM. "Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease." Ann Hum Genet 72.Pt 4 (July 2008): 443-453.
PMID
18318786
Source
pubmed
Published In
Annals of Human Genetics
Volume
72
Issue
Pt 4
Publish Date
2008
Start Page
443
End Page
453
DOI
10.1111/j.1469-1809.2008.00433.x

Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets.

Platelet-activating factor acetylhydrolase (PLA2G7) is a potent pro- and anti-inflammatory molecule that has been implicated in multiple inflammatory disease processes, including cardiovascular disease. The goal of this study was to investigate the genetic effects of PLA2G7 on coronary artery disease (CAD) risk in two large, independent datasets with CAD. Using a haplotype tagging (ht) approach, 19 ht single nucleotide polymorphisms (SNPs) were genotyped in CATHGEN case-control samples (cases = 806 and controls = 267) and in the GENECARD Family Study (n = 1101 families, 2954 individuals). Single SNP analysis using logistic regression revealed nine SNPs with significant association in all CATHGEN subjects (P = 0.0004-0.02). CATHGEN cases were further stratified into subgroups based on age of CAD onset (AOO) and severity of disease; 599 young affecteds (YA, AOO <56) and 207 old affected (OA, AOO >56). Significant genetic effects were observed in both OA and YA (P = 0.0001-0.02). The GENECARD probands demonstrated results similar to those seen in the YA CATHGEN cases (P = 0.002-0.05). Of the 19 SNPs genotyped, 3 SNPs result in nonsynonymous coding changes (I198T, A379V and R92H). Two of the coding SNPs, R92H and A379V, constitute two of the most significantly associated SNPs, even after Bonferroni correction and appear to represent independent associations (r(2) = 0.09). Multiple additional polymorphisms in low linkage disequilibrium with these coding SNPs were also strongly associated. In summary, PLA2G7 represents an important, potentially functional candidate in the pathophysiology of CAD based on replicated associations using two independent datasets and multiple statistical approaches. Further functional studies involving a combination of risk alleles are warranted.

Authors
Sutton, BS; Crosslin, DR; Shah, SH; Nelson, SC; Bassil, A; Hale, AB; Haynes, C; Goldschmidt-Clermont, PJ; Vance, JM; Seo, D; Kraus, WE; Gregory, SG; Hauser, ER
MLA Citation
Sutton, BS, Crosslin, DR, Shah, SH, Nelson, SC, Bassil, A, Hale, AB, Haynes, C, Goldschmidt-Clermont, PJ, Vance, JM, Seo, D, Kraus, WE, Gregory, SG, and Hauser, ER. "Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets." Hum Mol Genet 17.9 (May 1, 2008): 1318-1328.
PMID
18204052
Source
pubmed
Published In
Human Molecular Genetics
Volume
17
Issue
9
Publish Date
2008
Start Page
1318
End Page
1328
DOI
10.1093/hmg/ddn020

Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets

Authors
Sutton, BS; Crosslin, DR; Shah, SH; Nelson, SC; Bassil, A; Hale, AB; Haynes, C; Goldschmidt-Clermont, PJ; Vance, JM; Seo, D; Kraus, WE; Gregory, SG; Hauser, ER
MLA Citation
Sutton, BS, Crosslin, DR, Shah, SH, Nelson, SC, Bassil, A, Hale, AB, Haynes, C, Goldschmidt-Clermont, PJ, Vance, JM, Seo, D, Kraus, WE, Gregory, SG, and Hauser, ER. "Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets." HUMAN MOLECULAR GENETICS 17.9 (May 1, 2008): 1318-1328.
Source
wos-lite
Published In
Human Molecular Genetics
Volume
17
Issue
9
Publish Date
2008
Start Page
1318
End Page
1328
DOI
10.1093/hmg/ddn020

Differences in baseline characteristics and outcomes at 1- and 2-year follow-up of cancer survivors accrued via self-referral versus cancer registry in the FRESH START Diet and exercise trial.

Participant accrual to research studies is a challenge; oftentimes, advertisements are used to supplement cases ascertained through clinic caseloads and cancer registries. It is unknown, however, if cases ascertained through these two sources differ. In this study, we compared self-referred (n = 209) and registry-ascertained (n = 334) participants enrolled in FRESH START, a randomized controlled trial promoting a healthy diet and increased exercise among breast and prostate cancer survivors. The two groups were compared on baseline characteristics, adherence, attrition, and outcomes by study arm. Compared with participants enrolled from registries, self-referrals were significantly younger (54.1 +/- 10.4 versus 58.7 +/- 10.7 years), more likely to have later-stage disease and to have received chemotherapy (40% versus 19%), and more likely to report "fighting spirit" coping styles (50% versus 30%), lower quality-of-life (88.2 +/- 15.1 versus 92.0 +/- 12.9), fewer comorbid conditions (1.87 +/- 1.60 versus 2.24 +/- 1.78), and lower consumption of five or more daily servings of fruits and vegetables (35% versus 45%; P values <0.05). Although no differences in behavior change were observed between self-referred and registry-ascertained cases assigned to the tailored intervention arm, this was not the case within the attention control arm. Among those who received the attention control intervention of standardized materials in the public domain, self-referred versus registry-ascertained participants showed significantly greater increases in exercise at 1-year follow-up and significantly greater increases in fruit and vegetable consumption at both 1- and 2-year follow-up (P values <0.05). Several differences exist between self-referred and registry-ascertained participants, including motivation to respond to standardized educational materials, which appears significantly greater in self-referred populations.

Authors
Snyder, DC; Sloane, R; Lobach, D; Lipkus, IM; Peterson, B; Kraus, W; Demark-Wahnefried, W
MLA Citation
Snyder, DC, Sloane, R, Lobach, D, Lipkus, IM, Peterson, B, Kraus, W, and Demark-Wahnefried, W. "Differences in baseline characteristics and outcomes at 1- and 2-year follow-up of cancer survivors accrued via self-referral versus cancer registry in the FRESH START Diet and exercise trial." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 17.5 (May 2008): 1288-1294.
PMID
18483353
Source
epmc
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
17
Issue
5
Publish Date
2008
Start Page
1288
End Page
1294
DOI
10.1158/1055-9965.epi-07-0705

Chronic heart failure and exercise intolerance: the hemodynamic paradox.

Heart failure represents a major source of morbidity and mortality in industrialized nations. As the leading hospital discharge diagnosis in the United States in patients over the age of 65, it is also associated with substantial economic costs. While the acute symptoms of volume overload frequently precipitate inpatient admission, it is the symptoms of chronic heart failure, including fatigue, exercise intolerance and exertional dyspnea, that impact quality of life. Over the last two decades, research into the enzymatic, histologic and neurohumoral alterations seen with heart failure have revealed that hemodynamic derangements do not necessarily correlate with symptoms. This "hemodynamic paradox" is explained by alterations in the skeletal musculature that occur in response to hemodynamic derangements. Importantly, gender specific effects appear to modify both disease pathophysiology and response to therapy. The following review will discuss our current understanding of the systemic effects of heart failure before examining how exercise training and cardiac resynchronization therapy may impact disease course.

Authors
Nilsson, KR; Duscha, BD; Hranitzky, PM; Kraus, WE
MLA Citation
Nilsson, KR, Duscha, BD, Hranitzky, PM, and Kraus, WE. "Chronic heart failure and exercise intolerance: the hemodynamic paradox." Curr Cardiol Rev 4.2 (May 2008): 92-100.
PMID
19936283
Source
pubmed
Published In
Current cardiology reviews
Volume
4
Issue
2
Publish Date
2008
Start Page
92
End Page
100
DOI
10.2174/157340308784245757

Genetic and functional association of FAM5C with myocardial infarction.

BACKGROUND: We previously identified a 40 Mb region of linkage on chromosome 1q in our early onset coronary artery disease (CAD) genome-wide linkage scan (GENECARD) with modest evidence for linkage (n = 420, LOD 0.95). When the data are stratified by acute coronary syndrome (ACS), this modest maximum in the overall group became a well-defined LOD peak (maximum LOD of 2.17, D1S1589/D1S518). This peak overlaps a recently identified inflammatory biomarker (MCP-1) linkage region from the Framingham Heart Study (maximum LOD of 4.27, D1S1589) and a region of linkage to metabolic syndrome from the IRAS study (maximum LOD of 2.59, D1S1589/D1S518). The overlap of genetic screens in independent data sets provides evidence for the existence of a gene or genes for CAD in this region. METHODS: A peak-wide association screen (457 SNPs) was conducted of a region 1 LOD score down from the peak marker (168-198 Mb) in a linkage peak for acute coronary syndrome (ACS) on chromosome 1, within a family-based early onset coronary artery disease (CAD) sample (GENECARD). RESULTS: Polymorphisms were identified within the 'family with sequence similarity 5, member C' gene (FAM5C) that show genetic linkage to and are associated with myocardial infarction (MI) in GENECARD. The association was confirmed in an independent CAD case-control sample (CATHGEN) and strong association with MI was identified with single nucleotide polymorphisms (SNPs) in the 3' end of FAM5C. FAM5C genotypes were also correlated with expression of the gene in human aorta. Expression levels of FAM5C decreased with increasing passage of proliferating aortic smooth muscle cells (SMC) suggesting a role for this molecule in smooth muscle cell proliferation and senescence. CONCLUSION: These data implicate FAM5C alleles in the risk of myocardial infarction and suggest further functional studies of FAM5C are required to identify the gene's contribution to atherosclerosis.

Authors
Connelly, JJ; Shah, SH; Doss, JF; Gadson, S; Nelson, S; Crosslin, DR; Hale, AB; Lou, X; Wang, T; Haynes, C; Seo, D; Crossman, DC; Mooser, V; Granger, CB; Jones, CJH; Kraus, WE; Hauser, ER; Gregory, SG
MLA Citation
Connelly, JJ, Shah, SH, Doss, JF, Gadson, S, Nelson, S, Crosslin, DR, Hale, AB, Lou, X, Wang, T, Haynes, C, Seo, D, Crossman, DC, Mooser, V, Granger, CB, Jones, CJH, Kraus, WE, Hauser, ER, and Gregory, SG. "Genetic and functional association of FAM5C with myocardial infarction. (Published online)" BMC Med Genet 9 (April 22, 2008): 33-.
PMID
18430236
Source
pubmed
Published In
BMC Medical Genetics
Volume
9
Publish Date
2008
Start Page
33
DOI
10.1186/1471-2350-9-33

Relationships between adipose tissue and cytokine responses to a randomized controlled exercise training intervention.

Adipose-derived cytokines play a prominent role in mediating the metabolic consequences of obesity and excess body fat. Given this, we hypothesized that alterations in adipose tissue stores incurred with exercise training would be reflected in changes in systemic cytokine concentrations. The Studies of Targeted Risk Reduction Intervention through Defined Exercise, where pronounced changes in adipose tissue stores were observed in the absence of significant changes in dietary intake, provided an ideal setting in which to test this hypothesis. Participants were randomized to 6 months of inactivity or one of 3 types of aerobic exercise training regimens: low-amount-moderate-intensity, low-amount-vigorous-intensity, and high-amount-vigorous-intensity. Plasma samples were collected at baseline and 2 weeks after cessation of 6 months of exercise training or inactivity. In 189 participants, concentrations of 17 cytokines were measured using Bio-Plex Cytokine Assays (Bio-Rad, Hercules, CA); 10 additional cytokines were measured in 60 of these subjects. Of all cytokines tested, the only concentration changes that approached statistical significance were those for granulocyte monocyte-colony stimulating factor and vascular endothelial growth factor, which appeared to increase with training in the low-amount-high-intensity group only (P < .05 for both cytokines). No response to exercise training was noted for any additional cytokine in any of the groups. No relationships were observed between changes in cytokine concentrations and changes in fat mass or other measures of body habitus. In contradiction to our hypothesis, despite significant alterations in body composition, exercise training produced limited cytokine responses.

Authors
Huffman, KM; Slentz, CA; Bales, CW; Houmard, JA; Kraus, WE
MLA Citation
Huffman, KM, Slentz, CA, Bales, CW, Houmard, JA, and Kraus, WE. "Relationships between adipose tissue and cytokine responses to a randomized controlled exercise training intervention." Metabolism 57.4 (April 2008): 577-583.
PMID
18328363
Source
pubmed
Published In
Metabolism
Volume
57
Issue
4
Publish Date
2008
Start Page
577
End Page
583
DOI
10.1016/j.metabol.2007.11.023

Circulating metabolic intermediates are markers of insulin resistance in a population at risk for coronary heart disease

Authors
Huffman, KM; Shah, SH; Stevens, RD; Bain, JR; Kraus, WE
MLA Citation
Huffman, KM, Shah, SH, Stevens, RD, Bain, JR, and Kraus, WE. "Circulating metabolic intermediates are markers of insulin resistance in a population at risk for coronary heart disease." March 18, 2008.
Source
wos-lite
Published In
Circulation
Volume
117
Issue
11
Publish Date
2008

AHA-Recommended dietary intake patterns and lipid responses to exercise: Findings from the STRRIDE I study

Authors
Bales, CW; Huffman, KM; Hawk, VH; Henes, ST; Slentz, C; Johnson, J; Houmard, JA; Samsa, GP; Kraus, WE
MLA Citation
Bales, CW, Huffman, KM, Hawk, VH, Henes, ST, Slentz, C, Johnson, J, Houmard, JA, Samsa, GP, and Kraus, WE. "AHA-Recommended dietary intake patterns and lipid responses to exercise: Findings from the STRRIDE I study." March 18, 2008.
Source
wos-lite
Published In
Circulation
Volume
117
Issue
11
Publish Date
2008

Peripheral blood metabolic signatures are markers of coronary artery disease and myocardial infarction

Authors
Shah, SH; Bain, J; Muehlbauer, MJ; Stevens, RD; Wenner, BR; Naliboff, LC; Haynes, C; Ginsburg, GS; Hauser, ER; Newgard, CB; Kraus, WE
MLA Citation
Shah, SH, Bain, J, Muehlbauer, MJ, Stevens, RD, Wenner, BR, Naliboff, LC, Haynes, C, Ginsburg, GS, Hauser, ER, Newgard, CB, and Kraus, WE. "Peripheral blood metabolic signatures are markers of coronary artery disease and myocardial infarction." March 18, 2008.
Source
wos-lite
Published In
Circulation
Volume
117
Issue
11
Publish Date
2008

Blood-based gene expression signatures distinguish exercise training regimens

Authors
Dungan, JR; Lucas, J; West, M; Kraus, WE
MLA Citation
Dungan, JR, Lucas, J, West, M, and Kraus, WE. "Blood-based gene expression signatures distinguish exercise training regimens." March 18, 2008.
Source
wos-lite
Published In
Circulation
Volume
117
Issue
11
Publish Date
2008

Relationship between left ventricular dyssynchrony and functional capacity in moderate to severe heart failure: the HF-ACTION trial nuclear ancillary study

Authors
Trimble, MA; Whellan, D; O'Connor, CM; Velazquez, EJ; Kitzman, DW; Rendall, DS; Pagnanelli, RA; Iskandrian, AE; Ellis, SJ; Lee, KL; Kraus, WE; Borges-Neto, S
MLA Citation
Trimble, MA, Whellan, D, O'Connor, CM, Velazquez, EJ, Kitzman, DW, Rendall, DS, Pagnanelli, RA, Iskandrian, AE, Ellis, SJ, Lee, KL, Kraus, WE, and Borges-Neto, S. "Relationship between left ventricular dyssynchrony and functional capacity in moderate to severe heart failure: the HF-ACTION trial nuclear ancillary study." March 11, 2008.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
51
Issue
10
Publish Date
2008
Start Page
A167
End Page
A167

Expression profiling of peripheral blood cells identifies genes that distinguish patients with and without coronary artery stenosis

Authors
Wingrove, JA; Sehnert, AJ; Tingley, WG; Elashoff, M; Daniels, SE; Paoni, NF; Littleford, L; Nuttall, RL; Doctolero, M; Rosenberg, S; Buellesfeld, L; Grube, E; Newby, LK; Kraus, WE
MLA Citation
Wingrove, JA, Sehnert, AJ, Tingley, WG, Elashoff, M, Daniels, SE, Paoni, NF, Littleford, L, Nuttall, RL, Doctolero, M, Rosenberg, S, Buellesfeld, L, Grube, E, Newby, LK, and Kraus, WE. "Expression profiling of peripheral blood cells identifies genes that distinguish patients with and without coronary artery stenosis." March 11, 2008.
Source
wos-lite
Published In
JACC - Journal of the American College of Cardiology
Volume
51
Issue
10
Publish Date
2008
Start Page
A289
End Page
A289

Results of a diet/exercise feasibility trial to prevent adverse body composition change in breast cancer patients on adjuvant chemotherapy.

PURPOSE: Patients with breast cancer on adjuvant chemotherapy can experience weight gain and concurrent losses in muscle mass. Exercise interventions can prevent these changes, but time and travel pose barriers to participation. The Survivor Training for Enhancing Total Health (STRENGTH) trial assessed the feasibility and impact of 2 home-based interventions. PATIENTS AND METHODS: Ninety premenopausal patients with breast cancer on adjuvant chemotherapy were randomized to a calcium-rich diet (CA) intervention (attention control) or to 2 experimental arms: a CA + exercise (EX) arm or a CA + EX and high fruit and vegetable, low-fat diet (FVLF) arm. Exercise arms included aerobic and strength-training exercises. Body composition, weight status, waist circumference, dietary intake, physical activity, quality of life, anxiety, depression, serum lipids, sex hormone binding globulin, insulin, proinsulin, C-reactive protein, interleukin-1B, and tumor-necrosis factor receptor-II were measured at baseline and at 6-month follow-up. RESULTS: Accrual targets were achieved and modest attrition was observed (8.8%). Self-reports suggest increased calcium intakes in all arms, and higher fruit and vegetable and lower fat intake in the CA + EX + FVLF arm; no differences in physical activity were observed. While measures of adiposity were generally lower in the CA + EX + FVLF arm, the only significant difference was in percentage of body fat (arms and legs); change in scores (mean +/- standard deviation) were +0.7% +/- 2.3% (CA); +1.2% +/- 2.7% (CA + EX); and +0.1% +/- 2% (CA + EX + FVLF; P = .047). Lean body mass was largely preserved, even in the control arm (net gain of 452 g +/- 2395 g). No differences were observed in other endpoints. CONCLUSION: Diet and exercise interventions can prevent weight gain and adverse body composition changes, but more research is needed to determine optimally effective interventions that can be implemented during active treatment and that promote adherence.

Authors
Demark-Wahnefried, W; Case, LD; Blackwell, K; Marcom, PK; Kraus, W; Aziz, N; Snyder, DC; Giguere, JK; Shaw, E
MLA Citation
Demark-Wahnefried, W, Case, LD, Blackwell, K, Marcom, PK, Kraus, W, Aziz, N, Snyder, DC, Giguere, JK, and Shaw, E. "Results of a diet/exercise feasibility trial to prevent adverse body composition change in breast cancer patients on adjuvant chemotherapy." Clin Breast Cancer 8.1 (February 2008): 70-79.
PMID
18501061
Source
pubmed
Published In
Clinical Breast Cancer
Volume
8
Issue
1
Publish Date
2008
Start Page
70
End Page
79
DOI
10.3816/CBC.2008.n.005

Lack of Association Between Adrenergic Receptor Genotypes and Survival in Heart Failure Patients Treated With Carvedilol or Metoprolol

Objectives: This study investigated the role of adrenergic receptor genetics on transplant-free survival in heart failure (HF). Background: Discordant results exist for genetic associations between adrenergic receptor alleles and end points of β-blocker response in HF patients. Methods: We identified 637 patients enrolled in 2 U.S. cardiovascular genetic registries with HF and left ventricular systolic dysfunction who were discharged on β-blocker, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), and diuretic medications. End points were determined through the national Social Security Death Master File and transplant records. We genotyped 5 polymorphisms in 3 genes: ADRB1 (S49G, R389G), ADRB2 (G16R, Q27E), and ADRA2C (Del322-325) using 5′ nuclease assays and performed a multivariable clinical-genetic analysis. Results: A total of 190 events (29.8%) occurred over a median follow-up of 1,070 days. Multivariable analysis showed a significant effect of 4 clinical factors on survival: age (p = 0.006), gender (p = 0.005), ejection fraction (p = 0.0002), and hemoglobin (p = 0.00010). There was no significant effect of the polymorphisms or haplotypes analyzed on survival. Conclusions: Genotypes and haplotypes of ADRB1, ADRB2, and ADRA2C did not significantly affect survival in metoprolol-treated or carvedilol-treated HF patients in this study. These results complement the findings of 2 similarly designed previous studies, but do not replicate an association of ADRB2 haplotypes and survival. All 3 studies differ from a survival benefit reported for bucindolol-treated homozygous ADRB1 R389 individuals. This may be attributable to a drug-specific interaction between genotype and outcome with bucindolol that does not seem to occur with metoprolol or carvedilol. © 2008 American College of Cardiology Foundation.

Authors
Sehnert, AJ; Daniels, SE; Elashoff, M; Wingrove, JA; Burrow, CR; Horne, B; Muhlestein, JB; Donahue, M; Liggett, SB; Anderson, JL; Kraus, WE
MLA Citation
Sehnert, AJ, Daniels, SE, Elashoff, M, Wingrove, JA, Burrow, CR, Horne, B, Muhlestein, JB, Donahue, M, Liggett, SB, Anderson, JL, and Kraus, WE. "Lack of Association Between Adrenergic Receptor Genotypes and Survival in Heart Failure Patients Treated With Carvedilol or Metoprolol." Journal of the American College of Cardiology 52.8 (2008): 644-651.
PMID
18702968
Source
scival
Published In
JACC - Journal of the American College of Cardiology
Volume
52
Issue
8
Publish Date
2008
Start Page
644
End Page
651
DOI
10.1016/j.jacc.2008.05.022

Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis.

BACKGROUND: The molecular pathophysiology of coronary artery disease (CAD) includes cytokine release and a localized inflammatory response within the vessel wall. The extent to which CAD and its severity is reflected by gene expression in circulating cells is unknown. METHODS AND RESULTS: From an initial coronary catheterization cohort we identified 41 patients, comprising 27 cases with angiographically significant CAD and 14 controls without coronary stenosis. Whole-genome microarray analysis performed on peripheral-blood mononuclear cells yielded 526 genes with >1.3-fold differential expression (P<0.05) between cases and controls. Real-time polymerase chain reaction on 106 genes (the 50 most significant microarray genes and 56 additional literature genes) in an independent subset of 95 patients (63 cases, 32 controls) from the same cohort yielded 14 genes (P<0.05) that independently discriminated CAD state in a multivariable analysis that included clinical and demographic factors. From an independent second catheterization cohort, 215 patients were selected for real-time polymerase chain reaction-based replication. A case:control subset of 107 patients (86 cases, 21 controls) replicated 11 of the 14 multivariably significant genes from the first cohort. An analysis of the 14 genes in the entire set of 215 patients demonstrated that gene expression was proportional to maximal coronary artery stenosis (P<0.001 by ANOVA). CONCLUSIONS: Gene expression in peripheral-blood cells reflects the presence and extent of CAD in patients undergoing angiography.

Authors
Wingrove, JA; Daniels, SE; Sehnert, AJ; Tingley, W; Elashoff, MR; Rosenberg, S; Buellesfeld, L; Grube, E; Newby, LK; Ginsburg, GS; Kraus, WE
MLA Citation
Wingrove, JA, Daniels, SE, Sehnert, AJ, Tingley, W, Elashoff, MR, Rosenberg, S, Buellesfeld, L, Grube, E, Newby, LK, Ginsburg, GS, and Kraus, WE. "Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis." Circulation. Cardiovascular genetics 1.1 (2008): 31-38.
PMID
20031539
Source
scival
Published In
Circulation: Cardiovascular Genetics
Volume
1
Issue
1
Publish Date
2008
Start Page
31
End Page
38
DOI
10.1161/CIRCGENETICS.108.782730

Relationship of physical function to vastus lateralis capillary density and metabolic enzyme activity in elderly men and women

Background and aims: There are no data showing whether or not age-related declines in physical function are related to in vitro properties of human skeletal muscle. The purpose of this study was to determine whether physical function is independently associated with histologic and metabolic properties of skeletal muscle in elderly adults. Methods: The study was a cross-sectional observational study of 39 sedentary, older (60-85 yrs) men and women. A needle biopsy of the vastus lateralis for assessment of muscle fiber type, fiber area, capillary density and citrate synthase and aldolase activities was performed. Physical function tests included the Short Physical Performance Battery (balance, walking speed, and chair rise time), as well as self-reported disability. Results: Total fiber area (R=-0.41, p=0.02), number of Type II fibers (R=-0.33, p=0.05), and aldolase activity (R=-0.54, p=0.01) were inversely related to age. Persons who reported greater difficulty with daily activities had lower capillary density (R=-0.51, p=0.03) and lower citrate synthase activity (R=-0.66, p=0.03). Walking speed was directly related to fiber area (R=0.40, p=0.02), capillary density (R=0.39, p=0.03), citrate synthase (R=0.45, p=0.03) and aldolase (R=0.55, p<0.01) activities, even after adjustment for age, BMI and disease status. Conclusions: In older adults, skeletal muscle capillary density and metabolic enzymatic activity are independent predictors of lower extremity physical function. © 2008, Editrice Kurtis.

Authors
Nicklas, BJ; Leng, I; Delbono, O; Kitzman, DW; Marsh, AP; Hundley, WG; Lyles, MF; O'Rourke, KS; Annex, BH; Kraus, WE
MLA Citation
Nicklas, BJ, Leng, I, Delbono, O, Kitzman, DW, Marsh, AP, Hundley, WG, Lyles, MF, O'Rourke, KS, Annex, BH, and Kraus, WE. "Relationship of physical function to vastus lateralis capillary density and metabolic enzyme activity in elderly men and women." Aging Clinical and Experimental Research 20.4 (2008): 302-309.
PMID
18852542
Source
scival
Published In
Aging clinical and experimental research
Volume
20
Issue
4
Publish Date
2008
Start Page
302
End Page
309

Introduction: Exercise in patients with chronic heart failure

Authors
Keteyian, SJ; Kraus, WE
MLA Citation
Keteyian, SJ, and Kraus, WE. "Introduction: Exercise in patients with chronic heart failure." Heart Failure Reviews 13.1 (2008): 1-2.
PMID
17917809
Source
scival
Published In
Heart Failure Reviews
Volume
13
Issue
1
Publish Date
2008
Start Page
1
End Page
2
DOI
10.1007/s10741-007-9049-7

Exercise training amount and intensity effects on metabolic syndrome (from Studies of a Targeted Risk Reduction Intervention through Defined Exercise).

Although exercise improves individual risk factors for metabolic syndrome (MS), there is little research on the effect of exercise on MS as a whole. The objective of this study was to determine how much exercise is recommended to decrease the prevalence of MS. Of 334 subjects randomly assigned, 227 finished and 171 (80 women, 91 men) had complete data for all 5 Adult Treatment Panel III-defined MS risk factors and were included in this analysis. Subjects were randomly assigned to a 6-month control or 1 of 3 eight-month exercise training groups of (1) low amount/moderate intensity (equivalent to walking approximately 19 km/week), (2) low amount/vigorous intensity (equivalent to jogging approximately 19 km/week), or (3) high amount/vigorous intensity (equivalent to jogging approximately 32 km/week). The low-amount/moderate-intensity exercise prescription improved MS relative to inactive controls (p <0.05). However, the same amount of exercise at vigorous intensity was not significantly better than inactive controls, suggesting that lower-intensity exercise may be more effective in improving MS. The high-amount/vigorous-intensity group improved MS relative to controls (p <0.0001), the low-amount/vigorous-intensity group (p = 0.001), and the moderate-intensity group (p = 0.07), suggesting an exercise-dose effect. In conclusion, a modest amount of moderate-intensity exercise in the absence of dietary changes significantly improved MS and thus supported the recommendation that adults get 30 minutes of moderate-intensity exercise every day. A higher amount of vigorous exercise had greater and more widespread benefits. Finally, there was an indication that moderate-intensity may be better than vigorous-intensity exercise for improving MS.

Authors
Johnson, JL; Slentz, CA; Houmard, JA; Samsa, GP; Duscha, BD; Aiken, LB; McCartney, JS; Tanner, CJ; Kraus, WE
MLA Citation
Johnson, JL, Slentz, CA, Houmard, JA, Samsa, GP, Duscha, BD, Aiken, LB, McCartney, JS, Tanner, CJ, and Kraus, WE. "Exercise training amount and intensity effects on metabolic syndrome (from Studies of a Targeted Risk Reduction Intervention through Defined Exercise)." Am J Cardiol 100.12 (December 15, 2007): 1759-1766.
PMID
18082522
Source
pubmed
Published In
The American Journal of Cardiology
Volume
100
Issue
12
Publish Date
2007
Start Page
1759
End Page
1766
DOI
10.1016/j.amjcard.2007.07.027

Dietary carbohydrate intake and high-sensitivity C-reactive protein in at-risk women and men.

BACKGROUND: The quality and quantity of dietary carbohydrate intake, measured as dietary glycemic load (GL), are associated with a number of cardiovascular disease (CVD) risk factors and, in healthy young women, are related to increased high-sensitivity C-reactive protein (hsCRP) concentrations. Our objective was to determine if GL is related to hsCRP and other measures of CVD risk in a population of sedentary, overweight, dyslipidemic middle-aged women and men enrolled in an exercise intervention trial (STRRIDE). METHODS: This was a cross-sectional evaluation of the relationships between measures of dietary carbohydrate intake, calculated from food frequency questionnaire data, and CVD risk factors, including plasma hsCRP, measured in 171 subjects. RESULTS: After adjusting for energy intake, GL and other measures of carbohydrate intake were not independently related to hsCRP (P > .05 for all). In the analyses performed separately for each sex, only the quantity of carbohydrate intake was independently related to hsCRP (R2 = 0.28, P < .04), and this relationship was present for women but not for men. The strongest relationship identified between GL and any CVD risk factor was for cardiorespiratory fitness (R2 = 0.12, P < .02); an elevated GL was associated with a lower level of fitness in all subjects, and this relationship persisted even when the findings were adjusted for energy intake and sex (R2 = 0.48, P < .03). CONCLUSIONS: In middle-aged, sedentary, overweight to mildly obese, dyslipidemic individuals, consuming a diet with a low GL is associated with better cardiorespiratory fitness. Our findings suggest that the current literature relating carbohydrate intake and hsCRP should be viewed with skepticism, especially in the extension to at-risk populations that include men.

Authors
Huffman, KM; Orenduff, MC; Samsa, GP; Houmard, JA; Kraus, WE; Bales, CW
MLA Citation
Huffman, KM, Orenduff, MC, Samsa, GP, Houmard, JA, Kraus, WE, and Bales, CW. "Dietary carbohydrate intake and high-sensitivity C-reactive protein in at-risk women and men." Am Heart J 154.5 (November 2007): 962-968.
PMID
17967604
Source
pubmed
Published In
American Heart Journal
Volume
154
Issue
5
Publish Date
2007
Start Page
962
End Page
968
DOI
10.1016/j.ahj.2007.07.009

Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with peripheral arterial disease.

Intermittent claudication (IC) is the major clinical manifestation of peripheral arterial disease (PAD). Apoptosis has been linked to skeletal muscle pathophysiology in other chronic diseases such as congestive heart failure. This study tested the hypothesis that there would be increased levels of apoptosis in the skeletal muscle of patients with PAD compared with control individuals. In total, 26 individuals with PAD and 28 age-appropriate controls underwent studies of peak oxygen consumption (peak VO2) and a gastrocnemius muscle biopsy in the most symptomatic leg. Muscle biopsies were analyzed for apoptosis and caspase-3 activity. Patients with PAD had a reduced peak VO2 compared with controls. Apoptosis was increased in those with PAD compared with age-appropriate controls (3.83% +/- 2.6 vs 1.53% +/- 0.96; p < 0.001). In conclusion, PAD is associated with increased levels of apoptosis in the peripheral skeletal muscle. Further study is required to ascertain whether apoptosis plays a role in decreased functional capacity.

Authors
Mitchell, RG; Duscha, BD; Robbins, JL; Redfern, SI; Chung, J; Bensimhon, DR; Kraus, WE; Hiatt, WR; Regensteiner, JG; Annex, BH
MLA Citation
Mitchell, RG, Duscha, BD, Robbins, JL, Redfern, SI, Chung, J, Bensimhon, DR, Kraus, WE, Hiatt, WR, Regensteiner, JG, and Annex, BH. "Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with peripheral arterial disease." Vasc Med 12.4 (November 2007): 285-290.
PMID
18048464
Source
pubmed
Published In
Vascular Medicine
Volume
12
Issue
4
Publish Date
2007
Start Page
285
End Page
290
DOI
10.1177/1358863X07084858

A multi-stage evaluation of genetic association with early-onset coronary artery disease in MYLK gene

Authors
Wang, L; Hauser, ER; Crosslin, D; Nelson, S; Hale, AB; Gregory, S; Shah, SH; Kraus, WE; Goldschmidt-Clermont, PJ; Vance, JM; Invest, GENECARD
MLA Citation
Wang, L, Hauser, ER, Crosslin, D, Nelson, S, Hale, AB, Gregory, S, Shah, SH, Kraus, WE, Goldschmidt-Clermont, PJ, Vance, JM, and Invest, GENECARD. "A multi-stage evaluation of genetic association with early-onset coronary artery disease in MYLK gene." October 16, 2007.
Source
wos-lite
Published In
Circulation
Volume
116
Issue
16
Publish Date
2007
Start Page
806
End Page
806

Genomic convergence identified CAPG and VAMP8 as candidate genes for CAD

Authors
Wang, L; Hauser, ER; Crosslin, D; Nelson, S; Hale, AB; Gregory, SG; Shah, SH; Kraus, WE; Goldschmidt-Clermont, PJ; Vance, JM
MLA Citation
Wang, L, Hauser, ER, Crosslin, D, Nelson, S, Hale, AB, Gregory, SG, Shah, SH, Kraus, WE, Goldschmidt-Clermont, PJ, and Vance, JM. "Genomic convergence identified CAPG and VAMP8 as candidate genes for CAD." October 16, 2007.
Source
wos-lite
Published In
Circulation
Volume
116
Issue
16
Publish Date
2007
Start Page
807
End Page
807

Inactivity, exercise training and detraining, and plasma lipoproteins. STRRIDE: a randomized, controlled study of exercise intensity and amount.

Exercise has beneficial effects on lipoproteins. Little is known about how long the effects persist with detraining or whether the duration of benefit is effected by training intensity or amount. Sedentary, overweight subjects (n = 240) were randomized to 6-mo control or one of three exercise groups: 1) high-amount/vigorous-intensity exercise; 2) low-amount/vigorous-intensity exercise; or 3) low-amount/moderate-intensity exercise. Training consisted of a gradual increase in amount of exercise followed by 6 mo of exercise at the prescribed level. Exercise included treadmill, elliptical trainer, and stationary bicycle. The number of minutes necessary to expend the prescribed kilocalories per week (14 kcal x kg body wt(-1) x wk(-1) for both low-amount groups; 23 kcal x kg body wt(-1) x wk(-1) for high-amount group) was calculated for each subject. Average adherence was 83-92% for the three groups; minutes per week were 207, 125, and 203 and sessions per week were 3.6, 2.9, and 3.5 for high-amount/vigorous-intensity, low-amount/vigorous intensity, and low-amount/moderate-intensity groups, respectively. Plasma was obtained at baseline, 24 h, 5 days, and 15 days after exercise cessation. Continued inactivity resulted in significant increases in low-density lipoprotein (LDL) particle number, small dense LDL, and LDL-cholesterol. A modest amount of exercise training prevented this deterioration. Moderate-intensity but not vigorous-intensity exercise resulted in a sustained reduction in very-low-density lipoprotein (VLDL)-triglycerides over 15 days of detraining (P < 0.05). The high-amount group had significant improvements in high-density lipoprotein (HDL)-cholesterol, HDL particle size, and large HDL levels that were sustained for 15 days after exercise stopped. In conclusion, physical inactivity has profound negative effects on lipoprotein metabolism. Modest exercise prevented this. Moderate-intensity but not vigorous-intensity exercise resulted in sustained VLDL-triglyceride lowering. Thirty minutes per day of vigorous exercise, like jogging, has sustained beneficial effects on HDL metabolism.

Authors
Slentz, CA; Houmard, JA; Johnson, JL; Bateman, LA; Tanner, CJ; McCartney, JS; Duscha, BD; Kraus, WE
MLA Citation
Slentz, CA, Houmard, JA, Johnson, JL, Bateman, LA, Tanner, CJ, McCartney, JS, Duscha, BD, and Kraus, WE. "Inactivity, exercise training and detraining, and plasma lipoproteins. STRRIDE: a randomized, controlled study of exercise intensity and amount." J Appl Physiol (1985) 103.2 (August 2007): 432-442.
PMID
17395756
Source
pubmed
Published In
Journal of applied physiology (Bethesda, Md. : 1985)
Volume
103
Issue
2
Publish Date
2007
Start Page
432
End Page
442
DOI
10.1152/japplphysiol.01314.2006

Main outcomes of the FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention among breast and prostate cancer survivors.

PURPOSE: Cancer survivors are at increased risk for cardiovascular disease, diabetes, osteoporosis, and second primary tumors. Healthful lifestyle practices may improve the health and well-being of survivors. The FRESH START trial tested the efficacy of sequentially tailored versus standardized mailed materials on improving cancer survivors' diet and exercise behaviors. METHODS: Five hundred forty-three individuals with newly diagnosed locoregional breast or prostate cancer were recruited from 39 states and two provinces within North America. Participants were randomly assigned either to a 10-month program of tailored mailed print materials promoting fruit and vegetable (F&V) consumption, reducing total/saturated fat intake, and/or increasing exercise or to a 10-month program of nontailored mailed materials on diet and exercise available in the public domain. Telephone surveys conducted at baseline and 1 year assessed body mass index (BMI), dietary consumption, physical activity, and other psychosocial/behavioral indices. Clinical assessments were conducted on a 23% subsample; information was used to validate self-reports. RESULTS: Five hundred nineteen participants completed the 1-year follow-up (4.4% attrition; sample characteristics: 57 +/- 10.8 years old, 83% white, 56% female, 64% overweight/obese, and 0% underweight). Although both arms significantly improved their lifestyle behaviors (P < .05), significantly greater gains occurred in the FRESH START intervention versus the control arm (practice of two or more goal behaviors: +34% v +18%, P < .0001; exercise minutes per week: +59.3 v +39.2 minutes, P = .02; F&V per day: +1.1 v +0.6 servings, P = .01; total fat: -4.4% v -2.1%, P < .0001; saturated fat: -1.3% v -0.3%, P < .0001; and BMI: -0.3 v +0.1 kg/m2, respectively, P = .004). CONCLUSION: Mailed material interventions, especially those that are tailored, are effective in promoting healthful lifestyle changes among cancer survivors. Further study is needed to determine sustainability, cost to benefit, and generalizability to other cancer populations.

Authors
Demark-Wahnefried, W; Clipp, EC; Lipkus, IM; Lobach, D; Snyder, DC; Sloane, R; Peterson, B; Macri, JM; Rock, CL; McBride, CM; Kraus, WE
MLA Citation
Demark-Wahnefried, W, Clipp, EC, Lipkus, IM, Lobach, D, Snyder, DC, Sloane, R, Peterson, B, Macri, JM, Rock, CL, McBride, CM, and Kraus, WE. "Main outcomes of the FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention among breast and prostate cancer survivors." J Clin Oncol 25.19 (July 1, 2007): 2709-2718.
PMID
17602076
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
19
Publish Date
2007
Start Page
2709
End Page
2718
DOI
10.1200/JCO.2007.10.7094

Effect of exercise training on ventricular function, dyssynchrony, resting myocardial perfusion, and clinical outcomes in patients with heart failure: a nuclear ancillary study of Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION); design and rationale.

BACKGROUND: Technetium Tc 99m gated single photon emission computed tomography (SPECT) has become the cornerstone of noninvasive risk stratification in patients with ischemic heart disease, but its role in patients with heart failure is not as well established. STUDY DESIGN: This study is a substudy of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) trial--a National Institutes of Health/National Heart, Lung, and Blood Institute-funded randomized controlled trial--designed to evaluate the role of exercise training in patients with heart failure due to left ventricular dysfunction. For this substudy, a total of 300 patients distributed on an approximately 1:1 basis between the exercise training and usual care arms of HF-ACTION will undergo resting technetium Tc 99m gated SPECT at baseline and 12 months to compare changes in left ventricular function with exercise training. These changes, along with baseline data, will be correlated with changes in exercise parameters, inflammatory markers, and clinical outcomes: death, cardiovascular hospitalization, and quality of life scores. In a subset of patients, first-pass radionuclide ventriculography will be obtained to assess the relationship between ventricular dyssynchrony, ejection fraction, changes in exercise parameters, and outcomes. CONCLUSION: The role of nuclear imaging in patients with heart failure remains poorly defined. This substudy aims to harness the power of a large heart failure trial (HF-ACTION) to further delineate the utility of technetium Tc 99m gated SPECT imaging and first-pass radionuclide ventriculography for predicting important clinical outcomes in this population.

Authors
Bensimhon, DR; Adams, GL; Whellan, DJ; Pagnanelli, RA; Trimble, M; Lee, BA; Lee, KL; Ellis, SJ; Kraus, WE; Rendall, DS; Iskandrian, AE; O'Connor, CM; Borges-Neto, S; HF-ACTION Trial Investigators,
MLA Citation
Bensimhon, DR, Adams, GL, Whellan, DJ, Pagnanelli, RA, Trimble, M, Lee, BA, Lee, KL, Ellis, SJ, Kraus, WE, Rendall, DS, Iskandrian, AE, O'Connor, CM, Borges-Neto, S, and HF-ACTION Trial Investigators, . "Effect of exercise training on ventricular function, dyssynchrony, resting myocardial perfusion, and clinical outcomes in patients with heart failure: a nuclear ancillary study of Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION); design and rationale." Am Heart J 154.1 (July 2007): 46-53.
PMID
17584550
Source
pubmed
Published In
American Heart Journal
Volume
154
Issue
1
Publish Date
2007
Start Page
46
End Page
53
DOI
10.1016/j.ahj.2007.03.045

Morphology and ultrastructure of differentiating three-dimensional mammalian skeletal muscle in a collagen gel.

Because previous studies of three-dimensional skeletal muscle cultures have shown limited differentiation, the goal of this study was to establish conditions that would produce mature sarcomeres in a mammalian-derived skeletal muscle construct. We evaluated the differentiation of bioartificial muscles generated from C(2)C(12) myoblasts in a collagen gel cultured under steady, passive tension for up to 36 days. Staining for alpha-actinin, myosin, and F-actin indicated the presence of striated fibers as early as 6 days post-differentiation. Electron microscopy at 16 days post-differentiation revealed multinucleated myotubes with ordered, striated myofibers. At 33 days, the cultures contained collagen fibers and showed localization of paxillin at the fiber termini, suggesting that myotendinous junctions were forming. The present study demonstrates mature muscle synthesis in a three-dimensional system using a pure mammalian myoblast cell line. Our results suggest that this culture model can be used to evaluate the effects of various mechanical and biochemical cues on muscle development under normal and pathological conditions.

Authors
Rhim, C; Lowell, DA; Reedy, MC; Slentz, DH; Zhang, SJ; Kraus, WE; Truskey, GA
MLA Citation
Rhim, C, Lowell, DA, Reedy, MC, Slentz, DH, Zhang, SJ, Kraus, WE, and Truskey, GA. "Morphology and ultrastructure of differentiating three-dimensional mammalian skeletal muscle in a collagen gel." Muscle Nerve 36.1 (July 2007): 71-80.
PMID
17455272
Source
pubmed
Published In
Muscle and Nerve
Volume
36
Issue
1
Publish Date
2007
Start Page
71
End Page
80
DOI
10.1002/mus.20788

Effect of cyclic stretch on beta1D-integrin expression and activation of FAK and RhoA.

Integrins play a pivotal role in proliferation, differentiation, and survival in skeletal and cardiac myocytes. The beta(1D)-isoform of the beta(1)-integrin is specifically expressed in striated skeletal muscle. However, little is known about the role and the mechanisms by which the splice variant beta(1D)-integrin regulates myogenesis and mechanotransduction. We observed that cyclic mechanical stretch increases beta(1D)-integrin protein levels and activates the downstream cytoskeletal signaling proteins focal adhesion kinase (FAK) and RhoA. Elimination of native beta(1D)-integrin expression by RNA interference in immature developing myoblasts abolished stretch-induced increases in FAK phosphorylation and further downregulated RhoA activity. Blocking of beta(1D)-integrin expression prevented myocellular fusion to form multinucleated mature myotubes. Restoration of human beta(1D)-integrin expression in beta(1D)-integrin-deficient cells partially restored myotube formation. The onset of myofusion also requires the generation of nitric oxide (NO). The release of NO affects cytoskeletal proteins by mediating RhoA activity and protein degradation. Our previous study demonstrated that stretch-induced NO positively modulates mechanical properties of differentiating skeletal myocytes. We found a significant decrease in NO production and apparent elastic modulus in beta(1D)-integrin-deficient cells, suggesting signaling interactions between beta(1D)-integrin and neuronal NO synthase to mediate mechanotransduction and myogenesis in skeletal myocytes. These results suggest that, in addition to regulating differentiation, the beta(1D)-integrin isoform plays a critical role in the response of skeletal myoblasts to cyclic stretch by activating the downstream components of FAK and RhoA activity and affecting NO release.

Authors
Zhang, SJ; Truskey, GA; Kraus, WE
MLA Citation
Zhang, SJ, Truskey, GA, and Kraus, WE. "Effect of cyclic stretch on beta1D-integrin expression and activation of FAK and RhoA." Am J Physiol Cell Physiol 292.6 (June 2007): C2057-C2069.
PMID
17267546
Source
pubmed
Published In
American journal of physiology. Cell physiology
Volume
292
Issue
6
Publish Date
2007
Start Page
C2057
End Page
C2069
DOI
10.1152/ajpcell.00493.2006