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

Mentored Clinical Research Scholar Program

Administered By
Medicine, Infectious Diseases
Awarded By
National Institutes of Health
Role
Mentor
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

Publications:

Energy compensation and adiposity in humans.

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.
Authors
Careau, V; Halsey, LG; Pontzer, H; Ainslie, PN; Andersen, LF; Anderson, LJ; Arab, L; Baddou, I; Bedu-Addo, K; Blaak, EE; Blanc, S; Bonomi, AG; Bouten, CVC; Buchowski, MS; Butte, NF; Camps, SGJA; Close, GL; Cooper, JA; Das, SK; Cooper, R; Dugas, LR; Eaton, SD; Ekelund, U; Entringer, S; Forrester, T; Fudge, BW; Goris, AH; Gurven, M; Hambly, C; El Hamdouchi, A; Hoos, MB; Hu, S; Joonas, N; Joosen, AM; Katzmarzyk, P; Kempen, KP; Kimura, M; Kraus, WE; Kushner, RF; Lambert, EV; Leonard, WR; Lessan, N; Martin, CK; Medin, AC; Meijer, EP; Morehen, JC; Morton, JP; Neuhouser, ML; Nicklas, TA; Ojiambo, RM; Pietiläinen, KH; Pitsiladis, YP; Plange-Rhule, J; Plasqui, G; Prentice, RL; Rabinovich, RA; Racette, SB; Raichlen, DA; Ravussin, E; Reilly, JJ; Reynolds, RM; Roberts, SB; Schuit, AJ; Sjödin, AM; Stice, E; Urlacher, SS; Valenti, G; Van Etten, LM; Van Mil, EA; Wells, JCK; Wilson, G; Wood, BM; Yanovski, J; Yoshida, T; Zhang, X; Murphy-Alford, AJ; Loechl, CU; Luke, AH; Rood, J; Sagayama, H; Schoeller, DA; Wong, WW; Yamada, Y; Speakman, JR; IAEA DLW database group,
MLA Citation
Careau, Vincent, et al. “Energy compensation and adiposity in humans.Curr Biol, vol. 31, no. 20, Oct. 2021, pp. 4659-4666.e2. Pubmed, doi:10.1016/j.cub.2021.08.016.
URI
https://scholars.duke.edu/individual/pub1494988
PMID
34453886
Source
pubmed
Published In
Curr Biol
Volume
31
Published Date
Start Page
4659
End Page
4666.e2
DOI
10.1016/j.cub.2021.08.016

Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. RESULTS: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. CONCLUSIONS: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
Authors
Breeze, CE; Batorsky, A; Lee, MK; Szeto, MD; Xu, X; McCartney, DL; Jiang, R; Patki, A; Kramer, HJ; Eales, JM; Raffield, L; Lange, L; Lange, E; Durda, P; Liu, Y; Tracy, RP; Van Den Berg, D; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed MESA Multi-Omics Working Group,; Evans, KL; Kraus, WE; Shah, S; Tiwari, HK; Hou, L; Whitsel, EA; Jiang, X; Charchar, FJ; Baccarelli, AA; Rich, SS; Morris, AP; Irvin, MR; Arnett, DK; Hauser, ER; Rotter, JI; Correa, A; Hayward, C; Horvath, S; Marioni, RE; Tomaszewski, M; Beck, S; Berndt, SI; London, SJ; Mychaleckyj, JC; Franceschini, N
MLA Citation
Breeze, Charles E., et al. “Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.Genome Med, vol. 13, no. 1, Apr. 2021, p. 74. Pubmed, doi:10.1186/s13073-021-00877-z.
URI
https://scholars.duke.edu/individual/pub1481758
PMID
33931109
Source
pubmed
Published In
Genome Medicine
Volume
13
Published Date
Start Page
74
DOI
10.1186/s13073-021-00877-z

Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.

BACKGROUND: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. METHODS: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. RESULTS: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (-12.5 [95% CI, -14.9 to -10.2] mm Hg) compared with SEPA(-7.1 [-95% CI, 10.4 to -3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (-7.0 [95% CI, -8.5 to -4.0] mm Hg), with no change in SEPA (-0.3 [95% CI, -4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus -1.1 ms/mm Hg [95% CI, -2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus -0.2 ln ms2 [95% CI, -0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, -0.3 to 1.0] versus -1.4% [95% CI, -2.5 to -0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596). CONCLUSIONS: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02342808.
Authors
Blumenthal, JA; Hinderliter, AL; Smith, PJ; Mabe, S; Watkins, LL; Craighead, L; Ingle, K; Tyson, C; Lin, P-H; Kraus, WE; Liao, L; Sherwood, A
MLA Citation
Blumenthal, James A., et al. “Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.Circulation, vol. 144, no. 15, Oct. 2021, pp. 1212–26. Pubmed, doi:10.1161/CIRCULATIONAHA.121.055329.
URI
https://scholars.duke.edu/individual/pub1497196
PMID
34565172
Source
pubmed
Published In
Circulation
Volume
144
Published Date
Start Page
1212
End Page
1226
DOI
10.1161/CIRCULATIONAHA.121.055329

Associations between neighborhood socioeconomic cluster and hypertension, diabetes, myocardial infarction, and coronary artery disease within a cohort of cardiac catheterization patients.

BACKGROUND: Neighborhood-level socioeconomic status (SES) is associated with health outcomes, including cardiovascular disease and diabetes, but these associations are rarely studied across large, diverse populations. METHODS: We used Ward's Hierarchical clustering to define eight neighborhood clusters across North Carolina using 11 census-based indicators of SES, race, housing, and urbanicity and assigned 6992 cardiac catheterization patients at Duke University Hospital from 2001 to 2010 to clusters. We examined associations between clusters and coronary artery disease index > 23 (CAD), history of myocardial infarction, hypertension, and diabetes using logistic regression adjusted for age, race, sex, body mass index, region of North Carolina, distance to Duke University Hospital, and smoking status. RESULTS: Four clusters were urban, three rural, and one suburban higher-middle-SES (referent). We observed greater odds of myocardial infarction in all six clusters with lower or middle-SES. Odds of CAD were elevated in the rural cluster that was low-SES and plurality Black (OR 1.16, 95% CI 0.94-1.43) and in the rural cluster that was majority American Indian (OR 1.31, 95% CI 0.91-1.90). Odds of diabetes and hypertension were elevated in two urban and one rural low- and lower-middle SES clusters with large Black populations. CONCLUSIONS: We observed higher prevalence of cardiovascular disease and diabetes in neighborhoods that were predominantly rural, low-SES, and non-White, highlighting the importance of public health and healthcare system outreach into these communities to promote cardiometabolic health and prevent and manage hypertension, diabetes and coronary artery disease.
Authors
Weaver, AM; McGuinn, LA; Neas, L; Devlin, RB; Dhingra, R; Ward-Caviness, CK; Cascio, WE; Kraus, WE; Hauser, ER; Diaz-Sanchez, D
MLA Citation
URI
https://scholars.duke.edu/individual/pub1498749
PMID
34610283
Source
pubmed
Published In
American Heart Journal
Volume
243
Published Date
Start Page
201
End Page
209
DOI
10.1016/j.ahj.2021.09.013

Making Cardiopulmonary Exercise Testing Interpretable for Clinicians.

ABSTRACT: Cardiopulmonary exercise testing (CPET) is a dynamic clinical tool for determining the cause for a person's exercise limitation. CPET provides clinicians with fundamental knowledge of the coupling of external to internal respiration (oxygen and carbon dioxide) during exercise. Subtle perturbations in CPET parameters can differentiate exercise responses among individual patients and disease states. However, perhaps because of the challenges in interpretation given the amount and complexity of data obtained, CPET is underused. In this article, we review fundamental concepts in CPET data interpretation and visualization. We also discuss future directions for how to best use CPET results to guide clinical care. Finally, we share a novel three-dimensional graphical platform for CPET data that simplifies conceptualization of organ system-specific (cardiac, pulmonary, and skeletal muscle) exercise limitations. Our goal is to make CPET testing more accessible to the general medical provider and make the test of greater use in the medical toolbox.
Authors
Andonian, BJ; Hardy, N; Bendelac, A; Polys, N; Kraus, WE
MLA Citation
Andonian, Brian J., et al. “Making Cardiopulmonary Exercise Testing Interpretable for Clinicians.Curr Sports Med Rep, vol. 20, no. 10, Oct. 2021, pp. 545–52. Pubmed, doi:10.1249/JSR.0000000000000895.
URI
https://scholars.duke.edu/individual/pub1498292
PMID
34622820
Source
pubmed
Published In
Curr Sports Med Rep
Volume
20
Published Date
Start Page
545
End Page
552
DOI
10.1249/JSR.0000000000000895