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:

Interindividual Differences in Trainability and Moderators of Cardiorespiratory Fitness, Waist Circumference, and Body Mass Responses: A Large-Scale Individual Participant Data Meta-analysis.

Although many studies have assumed variability reflects variance caused by exercise training, few studies have examined whether interindividual differences in trainability are present following exercise training. The present individual participant data (IPD) meta-analysis sought to: (1) investigate the presence of interindividual differences in trainability for cardiorespiratory fitness (CRF), waist circumference, and body mass; and (2) examine the influence of exercise training and potential moderators on the probability that an individual will experience clinically important differences. The IPD meta-analysis combined data from 1879 participants from eight previously published randomized controlled trials. We implemented a Bayesian framework to: (1) test the hypothesis of interindividual differences in trainability by comparing variability in change scores between exercise and control using Bayes factors; and (2) compare posterior predictions of control and exercise across a range of moderators (baseline body mass index (BMI) and exercise duration, intensity, amount, mode, and adherence) to estimate the proportions of participants expected to exceed minimum clinically important differences (MCIDs) for all three outcomes. Bayes factors demonstrated a lack of evidence supporting a high degree of variance attributable to interindividual differences in trainability across all three outcomes. These findings indicate that interindividual variability in observed changes are likely due to measurement error and external behavioural factors, not interindividual differences in trainability. Additionally, we found that a larger proportion of exercise participants were expected to exceed MCIDs compared with controls for all three outcomes. Moderator analyses identified that larger proportions were associated with a range of factors consistent with standard exercise theory and were driven by mean changes. Practitioners should prescribe exercise interventions known to elicit large mean changes to increase the probability that individuals will experience beneficial changes in CRF, waist circumference and body mass.
Authors
Bonafiglia, JT; Swinton, PA; Ross, R; Johannsen, NM; Martin, CK; Church, TS; Slentz, CA; Ross, LM; Kraus, WE; Walsh, JJ; Kenny, GP; Goldfield, GS; Prud'homme, D; Sigal, RJ; Earnest, CP; Gurd, BJ
URI
https://scholars.duke.edu/individual/pub1526459
PMID
35781787
Source
pubmed
Published In
Sports Med
Published Date
DOI
10.1007/s40279-022-01725-9

Amount and intensity effects of exercise training alone versus a combined diet and exercise lifestyle intervention on health-related quality of life in the STRRIDE-PD randomized trial.

INTRODUCTION: To determine the relative contributions of various amounts and intensities of exercise alone to a combined lifestyle intervention on health-related quality of life (HrQoL) measures. RESEARCH DESIGN AND METHODS: Participants (n=162) were sedentary, overweight/obese, with pre-diabetes, and randomized to one of four 6-month interventions: (1) high amount/moderate intensity exercise-energy expenditure of 16 kcal/kg of body weight/week (KKW) at 50% oxygen consumption (V̇O2) reserve; (2) high/vigorous-16 KKW at 75% V̇O2 reserve; (3) low/moderate-10 KKW at 50% V̇O2 reserve; (4) low/moderate plus diet-10 KKW at 50% V̇O2 reserve plus a calorically restricted diet. The 36-Item Short-Form Survey (SF-36) and Satisfaction with Physical Function and Appearance (SPF/SPA) survey were assessed at baseline and post-intervention. Analyses of covariance determined differences in change scores among groups (p<0.05). Paired t-tests determined significant pre-intervention versus post-intervention scores within groups (p<0.05). RESULTS: Across the intervention, all groups (p<0.05) improved the physical component, SPF, and SPA scores. Only the low/moderate/diet group (p<0.001) significantly improved the mental component score. The high/vigorous group achieved 84.5% of the low/moderate/diet group effect for change in physical component score, and the low/moderate group achieved 83.7% of the low/moderate/diet group effect for change in mental component score. CONCLUSIONS: In general, a low amount of moderate intensity exercise combined with diet was the most effective intervention for improving HrQoL. Of the exercise-only interventions, vigorous intensity exercise provided the greatest impact on changes in physical function. On the other hand, low amounts of moderate intensity exercise provided the greatest impact on mental well-being, potentially being a more attainable exercise dose for previously sedentary individuals with pre-diabetes to achieve.
Authors
Collins, KA; Ross, LM; Piner, LW; Fos, LB; Slentz, CA; Bateman, LA; Willis, LH; Bales, CW; Siegler, IC; Wolever, RQ; Huffman, KM; Kraus, WE
MLA Citation
Collins, Katherine A., et al. “Amount and intensity effects of exercise training alone versus a combined diet and exercise lifestyle intervention on health-related quality of life in the STRRIDE-PD randomized trial.Bmj Open Diabetes Res Care, vol. 10, no. 1, Jan. 2022. Pubmed, doi:10.1136/bmjdrc-2021-002584.
URI
https://scholars.duke.edu/individual/pub1507483
PMID
35086944
Source
pubmed
Published In
Bmj Open Diabetes Research & Care
Volume
10
Published Date
DOI
10.1136/bmjdrc-2021-002584

Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.

BACKGROUND: Resistant hypertension is associated with increased risk of cognitive decline, stroke, and dementia. Lifestyle modification has been suggested to improve cognitive function through its salutary effects on vascular function. METHODS: Participants included 140 patients with resistant hypertension participating in the TRIUMPH trial. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA). Participants completed a 45-min cognitive test battery consisting of tests of Executive Functioning and Learning, Memory, and Processing Speed. Biomarkers of vascular [flow mediated dilation of the brachial artery (FMD)], microvascular, and cerebrovascular function were also collected, in addition to weight, fitness, and ambulatory blood pressure. RESULTS: Participants averaged 63 years of age, 48% women, 59% black, and obese [mean BMI = 36 kg/m 2 (SD = 4)]. Cognitive performance improved across the entire cohort during the 4-month trial [ t -scores pretreatment = 48.9 (48, 50) vs. posttreatment = 50.0 (49, 51), P  < 0.001]. Postintervention Executive Function/Learning composite performance was higher for participants in C-LIFE compared to SEPA ( d  = 0.37, P  = 0.039). C-LIFE intervention effects on Memory and Processing Speed were moderated by sex and baseline stroke risk, respectively ( P  = 0.026 and P  = 0.043 for interactions), such that males and participants with greater stroke risk showed the greatest cognitive changes. FMD [C-LIFE: +0.3% (-0.3, 1.0) vs. SEPA: -1.4% (-2.5, -0.3), P  = 0.022], and microvascular function [C-LIFE: 97 (65, 130) vs. SEPA: 025 (-75, 23), P  < 0.001] were improved in C-LIFE compared with SEPA, whereas cerebrovascular reactivity was not [C-LIFE: -0.2 (-0.4, 0) vs. SEPA: 0.1 (-0.2, 0.4), P  = 0.197). Mediation analyses suggested that increased executive function/learning was associated with reduced ambulatory SBP levels secondary to weight loss [indirect effect: B  = 0.25 (0.03, 0.71)]. CONCLUSION: Lifestyle modification individuals with resistant hypertension improves cognition, which appeared to be associated with reduced ambulatory SBP changes through weight loss. Cognitive improvements were accompanied by parallel improvements in endothelial and microvascular function.
Authors
Smith, PJ; Sherwood, A; Hinderliter, AL; Mabe, S; Watkins, LL; Craighead, L; Ingle, K; Tyson, C; Avorgbedor, F; Lin, P-H; Kraus, WE; Liao, L; Blumenthal, JA
MLA Citation
Smith, Patrick J., et al. “Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.J Hypertens, vol. 40, no. 7, July 2022, pp. 1359–68. Pubmed, doi:10.1097/HJH.0000000000003151.
URI
https://scholars.duke.edu/individual/pub1524774
PMID
35703293
Source
pubmed
Published In
J Hypertens
Volume
40
Published Date
Start Page
1359
End Page
1368
DOI
10.1097/HJH.0000000000003151

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

<h4>Background</h4>Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives.<h4>Objective</h4>To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140).<h4>Methods</h4>CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory.<h4>Results</h4>Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension.<h4>Conclusion</h4>Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.
Authors
Smith, PJ; Sherwood, A; Hinderliter, AL; Mabe, S; Tyson, C; Avorgbedor, F; Watkins, LL; Lin, P-H; Kraus, WE; Blumenthal, JA
MLA Citation
Smith, Patrick J., et al. “Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.Journal of Alzheimer’S Disease : Jad, vol. 87, no. 1, Jan. 2022, pp. 345–57. Epmc, doi:10.3233/jad-215522.
URI
https://scholars.duke.edu/individual/pub1512851
PMID
35275539
Source
epmc
Published In
Journal of Alzheimer'S Disease : Jad
Volume
87
Published Date
Start Page
345
End Page
357
DOI
10.3233/jad-215522

Exposures to low-levels of fine particulate matter are associated with acute changes in heart rate variability, cardiac repolarization, and circulating blood lipids in coronary artery disease patients.

Exposure to air pollution is a major risk factor for cardiovascular disease, disease risk factors, and mortality. Specifically, particulate matter (PM), and to some extent ozone, are contributors to these effects. In addition, exposures to these pollutants may be especially dangerous for susceptible populations. In this repeated-visit panel study, cardiovascular markers were collected from thirteen male participants with stable coronary artery disease. For 0-4 days prior to the health measurement collections, daily concentrations of fine PM (PM2.5) and ozone were obtained from local central monitoring stations located near the participant's homes. Then, single (PM2.5) and two-pollutant (PM2.5 and ozone) models were used to assess whether there were short-term changes in cardiovascular health markers. Per interquartile range increase in PM2.5, there were decrements in several heart rate variability metrics, including the standard deviation of the normal-to-normal intervals (lag 3, -5.8%, 95% confidence interval (CI) = -11.5, 0.3) and root-mean squared of successive differences (five day moving average, -8.1%, 95% CI = -15.0, -0.7). In addition, increases in PM2.5 were also associated with changes in P complexity (lag 1, 4.4%, 95% CI = 0.5, 8.5), QRS complexity (lag 1, 4.9%, 95% CI = 1.4, 8.5), total cholesterol (five day moving average, -2.1%, 95% CI = -4.1, -0.1), and high-density lipoprotein cholesterol (lag 2, -1.6%, 95% CI = -3.1, -0.1). Comparisons to our previously published work on ozone were conducted. We found that ozone affected inflammation and endothelial function, whereas PM2.5 influenced heart rate variability, repolarization, and lipids. All the health changes from these two studies were found at concentrations below the United States Environmental Protection Agency's National Ambient Air Quality Standards. Our results imply clear differences in the cardiovascular outcomes observed with exposure to the two ubiquitous air pollutants PM2.5 and ozone; this observation suggests different mechanisms of toxicity for these exposures.
Authors
Mirowsky, JE; Carraway, MS; Dhingra, R; Tong, H; Neas, L; Diaz-Sanchez, D; Cascio, WE; Case, M; Crooks, JL; Hauser, ER; Dowdy, ZE; Kraus, WE; Devlin, RB
MLA Citation
URI
https://scholars.duke.edu/individual/pub1525419
PMID
35780850
Source
pubmed
Published In
Environ Res
Volume
214
Published Date
Start Page
113768
DOI
10.1016/j.envres.2022.113768