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:

Health coaching and genetic risk testing in primary care: Randomized controlled trial.

OBJECTIVE: Accessible interventions are needed to prevent coronary heart disease (CHD) and Type 2 diabetes (T2D). This prospective, randomized, controlled trial evaluated remote health coaching (HC), genetic risk testing (GRT), or both added to standardized risk assessment (SRA) in at-risk military primary care patients. METHOD: Using a 2 × 2 factorial longitudinal design, 200 Air Force at-risk participants provided primary outcomes at baseline, 3-, 6- (HC endpoint), and 12-months. Secondary measures were taken less often. Per protocol analyses used linear models and logistic regression; intent-to-treat (ITT) analyses used mixed models. RESULTS: Compared with those not receiving HC, the HC group was 3.6 times more likely to report moderate to intense physical activity at 6-months (p = .0009), and 2.9 times more likely to report such at 12-months (p = .0065). ITT longitudinal model did not reach significance (p = .0885). The HC group reported lower emotional representations of illness at 6-weeks and lower depression at 6 months. There were no other significant findings. HC and GRT interacted; higher T2D risk participants receiving HC were 4.7 times more likely to report higher stage of change for exercise at 6-months, and lost 2.2 kg more by 12-months. Lower T2D risk participants receiving HC perceived greater control over CHD risk at 6-weeks, and averaged lower 6-month depression. CONCLUSIONS: Remote HC after SRA increased physical activity, which was sustained 6-months later. Incorporating GRT into SRA warrants further exploration regarding the potential to leverage HC for weight loss in elevated T2D risk participants, and for depression in lower T2D risk participants. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Authors
Wolever, RQ; Yang, Q; Maldonado, CJ; Armitage, NH; Musty, MD; Kraus, WE; Chang, J; Ginsburg, GS; Vorderstrasse, AA
MLA Citation
Wolever, Ruth Q., et al. “Health coaching and genetic risk testing in primary care: Randomized controlled trial.Health Psychol, May 2022. Pubmed, doi:10.1037/hea0001183.
URI
https://scholars.duke.edu/individual/pub1521583
PMID
35587890
Source
pubmed
Published In
Health Psychology
Published Date
DOI
10.1037/hea0001183

Exercise in Heart Failure

Authors
MLA Citation
Kraus, W. E. “Exercise in Heart Failure.” Heart Failure: A Companion to Braunwald’s Heart Disease Expert Consult, 2010, pp. 834–44. Scopus, doi:10.1016/B978-1-4160-5895-3.10057-9.
URI
https://scholars.duke.edu/individual/pub1529458
Source
scopus
Published Date
Start Page
834
End Page
844
DOI
10.1016/B978-1-4160-5895-3.10057-9

An antiplatelet response gene expression signature is associated with bleeding.

AIMS: Gene expression biosignatures may hold promise to individualize antiplatelet therapy in conjunction with current guidelines and risk scores. The Aspirin Response Signature (ARS) score is comprised of a weighted sum of correlated, prothrombotic gene transcripts measured in whole blood. In prior work where volunteers were exposed to aspirin 325  mg daily, higher ARS score was associated with lower platelet function; separately, in a clinical cohort of patients, higher ARS scores were associated with increased risk of adverse cardiovascular events. To better understand this apparent paradox, we measured ARS gene expression and score in volunteers to determine aspirin dose-response and ticagrelor relationships with ARS score and separately in patients to assess whether ARS is associated with incident bleeding. METHODS AND RESULTS: Blood samples were collected from volunteers (N = 188) who were exposed to 4 weeks of daily aspirin 81  mg, daily aspirin 325  mg, and/or twice-daily ticagrelor 90  mg. ARS scores were calculated from whole blood RNA qPCR, and platelet function and protein expression were assessed in platelet-rich plasma. In mixed linear regression models, aspirin 81  mg exposure was not associated with changes in ARS gene expression or score. Aspirin 325  mg exposure resulted in a 6.0% increase in ARS gene expression (p = 7.5 × 10-9 vs. baseline, p = 2.1 × 10-4 vs. aspirin 81  mg) and an increase in expression of platelet proteins corresponding to ARS genes. Ticagrelor exposure resulted in a 30.7% increase in ARS gene expression (p < 1 × 10-10 vs. baseline and each aspirin dose) and ARS score (p = 7.0 × 10-7 vs. baseline, p = 3.6 × 10-6 and 5.59 × 10-4 vs. aspirin 81  mg and 325  mg, respectively). Increases in ARS gene expression or score were associated with the magnitude of platelet inhibition across agents. To assess the association between ARS scores and incident bleeding, ARS scores were calculated in patients undergoing cardiac catheterization (N = 1421), of whom 25.4% experienced bleeding events over a median 6.2 years of follow-up. In a Cox model adjusting for demographics and baseline antithrombotic medication use, patients with ARS scores above the median had a higher risk of incident bleeding (HR 1.26 [95% CI 1.01-1.56], p = 0.038). CONCLUSIONS: The ARS is an Antiplatelet Response Signature which increases in response to greater platelet inhibition due to antiplatelet therapy and may represent a homeostatic mechanism to prevent bleeding. ARS scores could inform future strategies to prevent bleeding while maintaining antiplatelet therapy's benefit of ischemic cardiovascular event protection.
Authors
Friede, KA; Myers, RA; Gales, J; Zhbannikov, I; Ortel, TL; Shah, SH; Kraus, WE; Ginsburg, GS; Voora, D
MLA Citation
Friede, Kevin A., et al. “An antiplatelet response gene expression signature is associated with bleeding.Cardiovasc Res, May 2022. Pubmed, doi:10.1093/cvr/cvac079.
URI
https://scholars.duke.edu/individual/pub1521584
PMID
35576481
Source
pubmed
Published In
Cardiovasc Res
Published Date
DOI
10.1093/cvr/cvac079

Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.

Rheumatoid arthritis (RA) T cells drive autoimmune features via metabolic reprogramming that reduces oxidative metabolism. Exercise training improves cardiorespiratory fitness (i.e., systemic oxidative metabolism) and thus may impact RA T cell oxidative metabolic function. In this pilot study of RA participants, we took advantage of heterogeneous responses to a high-intensity interval training (HIIT) exercise program to identify relationships between improvements in cardiorespiratory fitness with changes in peripheral T cell and skeletal muscle oxidative metabolism. In 12 previously sedentary persons with seropositive RA, maximal cardiopulmonary exercise tests, fasting blood, and vastus lateralis biopsies were obtained before and after 10 weeks of HIIT. Following HIIT, improvements in RA cardiorespiratory fitness were associated with changes in RA CD4 + T cell basal and maximal respiration and skeletal muscle carnitine acetyltransferase (CrAT) enzyme activity. Further, changes in CD4 + T cell respiration were associated with changes in naïve CD4 + CCR7 + CD45RA + T cells, muscle CrAT, and muscle medium-chain acylcarnitines and fat oxidation gene expression profiles. In summary, modulation of cardiorespiratory fitness and molecular markers of skeletal muscle oxidative metabolism during exercise training paralleled changes in T cell metabolism. Exercise training that improves RA cardiorespiratory fitness may therefore be valuable in managing pathologically related immune and muscle dysfunction.Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.
Authors
Andonian, BJ; Koss, A; Koves, TR; Hauser, ER; Hubal, MJ; Pober, DM; Lord, JM; MacIver, NJ; St Clair, EW; Muoio, DM; Kraus, WE; Bartlett, DB; Huffman, KM
MLA Citation
Andonian, Brian J., et al. “Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.Sci Rep, vol. 12, no. 1, May 2022, p. 7450. Pubmed, doi:10.1038/s41598-022-11458-4.
URI
https://scholars.duke.edu/individual/pub1520201
PMID
35523821
Source
pubmed
Published In
Scientific Reports
Volume
12
Published Date
Start Page
7450
DOI
10.1038/s41598-022-11458-4

The Relation of Accelerometer-Measured Physical Activity and Serum Uric Acid Using the National Health and Nutrition Survey (NHANES) 2003-2004.

Objective: Gout is a crystal-induced inflammatory arthritis caused by elevated uric acid. Physical activity has the potential to reduce serum uric acid (SUA), thus improving the disease burden of gout. In this study, we examined the association of objectively-measured physical activity and SUA. Methods: A cross-sectional study was conducted using survey, laboratory, and accelerometer data from the 2003-2004 National Health and Nutrition Examination Survey (NHANES). SUA concentrations (mg/dL) were obtained during an initial exam, and then physical activity (kCal/day) was measured with 7 days of ActiGraph accelerometry in participants (n = 3,475) representative of the ambulatory, non-institutionalized US civilian population. Regression, including restricted cubic splines, was used to assess the relation of physical activity and SUA in bivariate and adjusted models. Covariates included age, gender, race/ethnicity, alcohol use, body mass index, renal function, and urate-lowering therapy. Results: In the bivariate model, physical activity was correlated with SUA concentrations and included a non-linear component (p < 0.01). In the adjusted model, linear splines were employed with a node at the SUA nadir of 5.37mg/dL; this occurred at 703 kCal/day of physical activity. The association of physical activity and SUA was negative from 0 to 703 kCal/day (p = 0.07) and positive >703 kCal/day (p < 0.01 for the change in slope). Conclusion: Physical activity and SUA are associated in a non-linear fashion, with a minimum estimated SUA at 703 kCal/day of objectively-measured physical activity. These findings raise intriguing questions about the use of physical activity as a potential adjunctive therapy in patients with gout, and further interventional studies are needed to elucidate the effects of moderate intensity exercise on SUA concentrations.
Authors
Smith, ID; Ross, LM; Gabaldon, JR; Holdgate, N; Pieper, CF; Ning, TC; Kraus, WE; Huffman, KM
MLA Citation
Smith, Isaac D., et al. “The Relation of Accelerometer-Measured Physical Activity and Serum Uric Acid Using the National Health and Nutrition Survey (NHANES) 2003-2004.Front Sports Act Living, vol. 3, 2021, p. 775398. Pubmed, doi:10.3389/fspor.2021.775398.
URI
https://scholars.duke.edu/individual/pub1509742
PMID
35098119
Source
pubmed
Published In
Frontiers in Sports and Active Living
Volume
3
Published Date
Start Page
775398
DOI
10.3389/fspor.2021.775398