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
Role
Co Investigator
Start Date
End Date

Publications:

Impact on cardiometabolic risk of a weight loss intervention with higher protein from lean red meat: Combined results of 2 randomized controlled trials in obese middle-aged and older adults.

BACKGROUND: The recognized benefits of a higher protein diet on muscle mass and strength in older adults are tempered by concerns of the potentially negative cardiometabolic impact of dietary sources of animal protein. OBJECTIVE: The aim of this study was to explore the cardiometabolic impact of 2 weight reduction diets: a higher protein diet, providing balanced portions of lean beef and pork throughout the day, vs. a diet following the Recommended Daily Allowance level of protein in obese middle-aged and older adults. METHODS: Data from Measuring Eating, Activity and Strength: Understanding the Response-Using Protein and Protein Optimization in Women Enables Results-Using Protein were combined for the present analysis. Subjects were randomly assigned to a 6-month weight loss diet (500 kcal deficit) and prescribed a Recommended Daily Allowance level of protein (0.8 g protein/kg BW), control group, or a higher level of protein (1.2 g protein/kg BW), protein group. For the protein group, lean, high-quality protein was evenly distributed between meals or balanced throughout the day (30 g protein/meal). The following cardiometabolic markers were quantified by nuclear magnetic resonance spectroscopy: lipids, lipoproteins, GlycA, trimethylamine-N-oxide, betaine, branched-chain amino acids, and lipoprotein insulin resistance index scores. RESULTS: In both groups (control [n = 27] and protein [n = 53]), there were significant (P ≤ .05) changes from baseline in weight loss (-6.2% and -7.2%), distance walked (+53.1 and +75.0 meters), and fasting plasma glucose (-7.5 and -6.2 mg/dL), respectively. At endpoint, protein group had significantly (P ≤ .05) lower triglycerides (-17.3 mg/dL), large very-low-density lipoprotein particle concentration (VLDL-P; -1.2 nmol/L), total low-density lipoprotein particle concentration (LDL-P; -67.8 nmol/L), small LDL-P (-59.4 nmol/L) and lipoprotein insulin resistance index (-5.9), whereas control group had significantly (P ≤ .05) lower GlycA (-13.1 μmol/L), total VLDL-P (-7.9 nmol/L), and small VLDL-P (-7.0 nmol/L). Differences between groups were observed for small VLDL-P (P = .02) and protein intake (P < .0001). CONCLUSIONS: These findings suggest that a hypocaloric diet with either traditional (0.8 g/kg BW/d) or higher protein (1.2 g/kg BW/d; predominantly from lean red meat) content improves risk markers of cardiovascular disease and type II diabetes in obese middle-aged and older adults. Both diets were also associated with improved physical function, and neither had an adverse impact on cardiometabolic outcomes.
Authors
Porter Starr, KN; Connelly, MA; Orenduff, MC; McDonald, SR; Sloane, R; Huffman, KM; Kraus, WE; Bales, CW
MLA Citation
Porter Starr, Kathryn N., et al. “Impact on cardiometabolic risk of a weight loss intervention with higher protein from lean red meat: Combined results of 2 randomized controlled trials in obese middle-aged and older adults..” J Clin Lipidol, vol. 13, no. 6, Nov. 2019, pp. 920–31. Pubmed, doi:10.1016/j.jacl.2019.09.012.
URI
https://scholars.duke.edu/individual/pub1422311
PMID
31771921
Source
pubmed
Published In
Journal of Clinical Lipidology
Volume
13
Published Date
Start Page
920
End Page
931
DOI
10.1016/j.jacl.2019.09.012

Evaluating Individual Level Responses to Exercise for Health Outcomes in Overweight or Obese Adults.

Background: Understanding group responses to a given exercise exposure is becoming better developed; however, understanding of individual responses to specific exercise exposures is significantly underdeveloped and must advance before personalized exercise medicine can become a functional reality. Herein, utilizing data from the STRRIDE studies, we address some of the key issues surrounding our efforts to develop better understanding of individual exercise responsiveness. Methods: We assessed individual cardiometabolic and cardiorespiratory fitness responses in subjects successfully completing STRRIDE I (n = 227) and STRRIDE II (n = 155). Subjects were previously sedentary, overweight or obese men and women with mild-to-moderate dyslipidemia. Subjects were randomized to either an inactive control group or to an exercise training program. Training groups varied to test the differential effects of exercise amount, intensity, and mode on cardiometabolic health outcomes. Measures included fasting plasma glucose, insulin, and lipids; blood pressure, minimal waist circumference, visceral adipose tissue, and peak VO2. Absolute change scores were calculated for each subject as post-intervention minus pre-intervention values in order to evaluate the heterogeneity of health factor responsiveness to exercise training. Results: For subjects completing one of the aerobic training programs, change in peak VO2 ranged from a loss of 37% to a gain of 77%. When ranked by magnitude of change, we observed discordant responses among changes in peak VO2 with changes in visceral adipose tissue, HDL-C, triglycerides, and fasting plasma insulin. There was also not a clear, direct relationship observed between magnitudes of individual response in the aforementioned variables with aerobic training adherence levels. This same pattern of highly variable and discordant responses was displayed even when considering subjects with adherence levels greater than 70%. Conclusion: Our findings illustrate the unclear relationship between magnitude of individual response for a given outcome with training adherence and specific exercise exposure. These discordant and heterogeneous responses highlight the difficult nature of developing understanding for how individuals will respond to any given exposure. Further investigation into the biological, physiological, and genetics factors affecting individual responsiveness is vital to making personalized exercise medicine a reality.
Authors
Ross, LM; Slentz, CA; Kraus, WE
MLA Citation
Ross, Leanna M., et al. “Evaluating Individual Level Responses to Exercise for Health Outcomes in Overweight or Obese Adults..” Front Physiol, vol. 10, 2019. Pubmed, doi:10.3389/fphys.2019.01401.
URI
https://scholars.duke.edu/individual/pub1423278
PMID
31798463
Source
pubmed
Published In
Frontiers in Physiology
Volume
10
Published Date
Start Page
1401
DOI
10.3389/fphys.2019.01401

Short-Term Changes in Cardiorespiratory Fitness in Response to Exercise Training and the Association with Long-Term Cardiorespiratory Fitness Decline: The STRRIDE Reunion Study.

Background Substantial heterogeneity exists in the cardiorespiratory fitness (CRF) change in response to exercise training, and its long-term prognostic implication is not well understood. We evaluated the association between the short-term supervised training-related changes in CRF and CRF levels 10 years later. Methods and Results STRRIDE (Studies of a Targeted Risk Reduction Intervention Through Defined Exercise) trial participants who were originally randomized to exercise training for 8 months and participated in the 10-year follow-up visit were included. CRF levels were measured at baseline, after training (8 months), and at 10-year follow-up as peak oxygen uptake (vo2, mL/kg per min) using the maximal treadmill test. Participants were stratified into low, moderate, and high CRF response groups according to the training regimen-specific tertiles of CRF change. The study included 80 participants (age: 52 years; 35% female). At 10-year follow-up, the high-response CRF group had the least decline in CRF compared with the moderate- and low-response CRF groups (-0.35 versus -2.20 and -4.25 mL/kg per minute, respectively; P=0.02). This result was largely related to the differential age-related changes in peak oxygen pulse across the 3 groups (0.58, -0.23, and -0.86 mL/beat, respectively; P=0.03) with no difference in the peak heart rate change. In adjusted linear regression analysis, high response was significantly associated with greater CRF at follow-up independent of other baseline characteristics (high versus low [reference] CRF response: standard β=0.25; P=0.004). Conclusions Greater CRF improvement in response to short-term training is associated with higher CRF levels 10 years later. Lack of CRF improvements in response to short-term training may identify individuals at risk for exaggerated CRF decline with aging.
Authors
Pandey, A; Johnson, JL; Slentz, CA; Ross, LM; Agusala, V; Berry, JD; Kraus, WE
MLA Citation
URI
https://scholars.duke.edu/individual/pub1415078
PMID
31597504
Source
pubmed
Published In
Journal of the American Heart Association
Volume
8
Published Date
Start Page
e012876
DOI
10.1161/JAHA.119.012876

Systolic Blood Pressure and Socioeconomic Status in a large multi-study population.

The present study used harmonized data from eight studies (N = 28,891) to examine the association between socioeconomic status (SES) and resting systolic blood pressure (SBP). The study replicates and extends our prior work on this topic by examining potential moderation of this association by race and gender. We also examined the extent to which body mass index (BMI), waist circumference (WC), and smoking might explain the association between SES and SBP. Data were available from six race/gender groups: 9200 Black women; 2337 Black men; 7248 White women; 6519 White men; 2950 Hispanic women; and 637 Hispanic men. Multivariable regression models showed that greater annual household income was associated with lower SBP in all groups except Hispanic men. The magnitude and form of this negative association differed across groups, with White women showing the strongest linear negative association. Among Black men and Hispanic women, the association was curvilinear: relatively flat among lower income levels, but then negative among higher income ranges. Education also was independently, negatively related to SBP, though evidence was weaker for race and gender differences in the strength of the association. Higher BMI and WC were associated with higher SBP, and current smoking with lower SBP. Inclusion of these risk factors resulted in only a modest change in the magnitude of the SBP and SES relation, accounting on average about 0.4 mmHg of the effect of income and 0.2 mmHg of the effect of education-effects unlikely to be clinically significant. Further understanding of mechanisms underlying the association between SBP and SES may improve risk stratification in clinical settings and potentially inform interventions aimed at reductions in social disparities in health.
Authors
Brummett, BH; Babyak, MA; Jiang, R; Huffman, KM; Kraus, WE; Singh, A; Hauser, ER; Siegler, IC; Williams, RB
MLA Citation
Brummett, Beverly H., et al. “Systolic Blood Pressure and Socioeconomic Status in a large multi-study population..” Ssm Popul Health, vol. 9, Dec. 2019. Pubmed, doi:10.1016/j.ssmph.2019.100498.
URI
https://scholars.duke.edu/individual/pub1416626
PMID
31650001
Source
pubmed
Published In
Ssm Population Health
Volume
9
Published Date
Start Page
100498
DOI
10.1016/j.ssmph.2019.100498

Association Between Insulin Resistance, Plasma Leptin, and Neurocognition in Vascular Cognitive Impairment.

BACKGROUND: Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated. OBJECTIVE: To examine metabolic mechanisms underlying the association between obesity and neurocognition. METHODS: We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used. RESULTS: Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p = 0.043), CRP (p < 0.001), and leptin (p < 0.001) compared with men. Higher BMI levels were associated with worse performance on measures of Executive Function (β= -0.16, p = 0.024) and Verbal Memory (β= -0.16, p = 0.030), but not Visual Memory (β= 0.05, p = 0.500). Worse metabolic biomarker profiles also were associated with lower Executive Function (β= -0.12, p = 0.050). Mediation analyses suggested leptin was a plausible candidate as a mediator between BMI and Executive Function. CONCLUSIONS: In overweight and obese adults with vascular CIND, the association between greater weight and poorer executive function may be mediated by higher leptin resistance.
Authors
Smith, PJ; Mabe, S; Sherwood, A; Babyak, MA; Doraiswamy, PM; Welsh-Bohmer, KA; Kraus, W; Burke, J; Hinderliter, A; Blumenthal, JA
MLA Citation
Smith, Patrick J., et al. “Association Between Insulin Resistance, Plasma Leptin, and Neurocognition in Vascular Cognitive Impairment..” J Alzheimers Dis, vol. 71, no. 3, 2019, pp. 921–29. Pubmed, doi:10.3233/JAD-190569.
URI
https://scholars.duke.edu/individual/pub1406460
PMID
31476159
Source
pubmed
Published In
J Alzheimers Dis
Volume
71
Published Date
Start Page
921
End Page
929
DOI
10.3233/JAD-190569