William Kraus

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:

Richard and Pat Johnson University Distinguished Professor

Medicine, Cardiology
School of Medicine

Professor of Medicine

Medicine, Cardiology
School of Medicine

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

Duke University

Medical Resident, Medicine

Duke University

Fellow in Cardiology, Medicine

Duke University

Grants:

The Role of Ankyrin-B Mutations in Premature Senescence

Administered By
Medicine, Cardiology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Epigenetic Mechanisms Promoting Longevity

Administered By
Duke Molecular Physiology Institute
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Systemic Inflammation in Microphysiological Models of Muscle and Vascular Disease

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Circulatory system and integrated muscle tissue for drug and tissue toxicity

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

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
Awarded By
Bioiberica, S.A.
Role
Co Investigator
Start Date
End Date

Publications:

Lipoprotein Subclasses Associated With High-Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial.

BACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high-risk coronary atherosclerotic plaque (HRP). Blood-based biomarkers that associate with imaging-defined HRP and predict MACE are lacking. METHODS AND RESULTS Nuclear magnetic resonance-based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP-associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high-density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56-0.85]; P<0.001) and medium HDL (OR, 0.84 [95% CI, 0.72-0.98]; P=0.028) and HDL size (OR, 0.82 [95% CI, 0.69-0.96]; P=0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; P=0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88-0.94]; P<0.001). CONCLUSIONS Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT01174550.
Authors
McGarrah, RW; Ferencik, M; Giamberardino, SN; Hoffmann, U; Foldyna, B; Karady, J; Ginsburg, GS; Kraus, WE; Douglas, PS; Shah, SH
MLA Citation
McGarrah, Robert W., et al. “Lipoprotein Subclasses Associated With High-Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial.J Am Heart Assoc, Dec. 2022, p. e026662. Pubmed, doi:10.1161/JAHA.122.026662.
URI
https://scholars.duke.edu/individual/pub1560568
PMID
36565187
Source
pubmed
Published In
Journal of the American Heart Association
Published Date
Start Page
e026662
DOI
10.1161/JAHA.122.026662

Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.

Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.
Authors
Avorgbedor, F; Blumenthal, JA; Hinderliter, A; Ingle, K; Lin, P-H; Craighead, L; Tyson, C; Kraus, W; Sherwood, A; Smith, PJ
MLA Citation
Avorgbedor, Forgive, et al. “Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.J Clin Hypertens (Greenwich), Dec. 2022. Pubmed, doi:10.1111/jch.14591.
URI
https://scholars.duke.edu/individual/pub1560567
PMID
36541028
Source
pubmed
Published In
J Clin Hypertens (Greenwich)
Published Date
DOI
10.1111/jch.14591

Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.

BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.
Authors
Paluch, AE; Bajpai, S; Ballin, M; Bassett, DR; Buford, TW; Carnethon, MR; Chernofsky, A; Dooley, EE; Ekelund, U; Evenson, KR; Galuska, DA; Jefferis, BJ; Kong, L; Kraus, WE; Larson, MG; Lee, I-M; Matthews, CE; Newton, RL; Nordström, A; Nordström, P; Palta, P; Patel, AV; Pettee Gabriel, K; Pieper, CF; Pompeii, L; Rees-Punia, E; Spartano, NL; Vasan, RS; Whincup, PH; Yang, S; Fulton, JE; Steps for Health Collaborative,
MLA Citation
Paluch, Amanda E., et al. “Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.Circulation, Dec. 2022. Pubmed, doi:10.1161/CIRCULATIONAHA.122.061288.
URI
https://scholars.duke.edu/individual/pub1560632
PMID
36537288
Source
pubmed
Published In
Circulation
Published Date
DOI
10.1161/CIRCULATIONAHA.122.061288

The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes.

BACKGROUND: Epigenetic age is a DNA methylation-based biomarker of aging that is accurate across the lifespan and a range of cell types. The difference between epigenetic age and chronological age, termed age acceleration (AA), is a strong predictor of lifespan and healthspan. The predictive capabilities of AA for all-cause mortality have been evaluated in the general population; however, its utility is less well evaluated in those with chronic conditions. Additionally, the pathophysiologic pathways whereby AA predicts mortality are unclear. We hypothesized that AA predicts mortality in individuals with underlying cardiovascular disease; and the association between AA and mortality is mediated, in part, by vascular and cardiometabolic measures. METHODS: We evaluated 562 participants in an urban, three-county area of central North Carolina from the CATHGEN cohort, all of whom received a cardiac catheterization procedure. We analyzed three AA biomarkers, Horvath epigenetic age acceleration (HAA), phenotypic age acceleration (PhenoAA), and Grim age acceleration (GrimAA), by Cox regression models, to assess whether AAs were associated with all-cause mortality. We also evaluated if these associations were mediated by vascular and cardiometabolic outcomes, including left ventricular ejection fraction (LVEF), blood cholesterol concentrations, angiopoietin-2 (ANG2) protein concentration, peripheral artery disease, coronary artery disease, diabetes, and hypertension. The total effect, direct effect, indirect effect, and percentage mediated were estimated using pathway mediation tests with a regression adjustment approach. RESULTS: PhenoAA (HR = 1.05, P < 0.0001), GrimAA (HR = 1.10, P < 0.0001) and HAA (HR = 1.03, P = 0.01) were all associated with all-cause mortality. The association of mortality and PhenoAA was partially mediated by ANG2, a marker of vascular function (19.8%, P = 0.016), and by diabetes (8.2%, P = 0.043). The GrimAA-mortality association was mediated by ANG2 (12.3%, P = 0.014), and showed weaker evidence for mediation by LVEF (5.3%, P = 0.065). CONCLUSIONS: Epigenetic age acceleration remains strongly predictive of mortality even in individuals already burdened with cardiovascular disease. Mortality associations were mediated by ANG2, which regulates endothelial permeability and angiogenic functions, suggesting that specific vascular pathophysiology may link accelerated epigenetic aging with increased mortality risks.
Authors
Jiang, R; Hauser, ER; Kwee, LC; Shah, SH; Regan, JA; Huebner, JL; Kraus, VB; Kraus, WE; Ward-Caviness, CK
MLA Citation
Jiang, Rong, et al. “The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes.Clin Epigenetics, vol. 14, no. 1, Dec. 2022, p. 165. Pubmed, doi:10.1186/s13148-022-01380-x.
URI
https://scholars.duke.edu/individual/pub1559076
PMID
36461124
Source
pubmed
Published In
Clin Epigenetics
Volume
14
Published Date
Start Page
165
DOI
10.1186/s13148-022-01380-x

Clinical Predictors of Adherence to Exercise Training Among Individuals With Heart Failure: THE HF-ACTION STUDY.

PURPOSE: Suboptimal adherence is a major limitation to achieving the benefits of exercise interventions, and our ability to predict and improve adherence is limited. The purpose of this analysis was to identify baseline clinical and demographic characteristics predicting exercise training adherence in the HF-ACTION study cohort. METHODS: Adherence to exercise training, defined by the total duration of exercise performed (min/wk), was evaluated in 1159 participants randomized to the HF-ACTION exercise intervention. More than 50 clinical, demographic, and exercise testing variables were considered in developing a model of the min/wk end point for 1-3 mo (supervised training) and 10-12 mo (home-based training). RESULTS: In the multivariable model for 1-3 mo, younger age, lower income, more severe mitral regurgitation, shorter 6-min walk test distance, lower exercise capacity, and Black or African American race were associated with poorer exercise intervention adherence. No variable accounted for >2% of the variance and the adjusted R2 for the final model was 0.14. Prediction of adherence was similarly limited for 10-12 mo. CONCLUSIONS: Clinical and demographic variables available at the initiation of exercise training provide very limited information for identifying patients with heart failure who are at risk for poor adherence to exercise interventions.
Authors
Collins, KA; Reeves, GR; Miller, NH; Whellan, DJ; O'Connor, CM; Marcus, BH; Kitzman, DW; Kraus, WE; HF-ACTION Investigators,
MLA Citation
Collins, Katherine A., et al. “Clinical Predictors of Adherence to Exercise Training Among Individuals With Heart Failure: THE HF-ACTION STUDY.J Cardiopulm Rehabil Prev, Dec. 2022. Pubmed, doi:10.1097/HCR.0000000000000757.
URI
https://scholars.duke.edu/individual/pub1558895
PMID
36479935
Source
pubmed
Published In
J Cardiopulm Rehabil Prev
Published Date
DOI
10.1097/HCR.0000000000000757