• Measure endothelial function determined by brachial artery reactivity to stress, at baseline/following 6m program participation comparison of change between subj randomized to exercise with weight-loss intervention vs. those randomized to exerci...
  

Behavioral: Exercise
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Behavioral: Weight Loss
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Employees in developed societies are becoming increasingly sedentary at work and at home due to technological advances. Physical inactivity coupled with excess intake of calorie-rich foods are responsible for the epidemic of obesity. In population cohorts, physical inactivity and obesity increase the risk of cardiovascular disease and death. Because of the impact on productivity and health care costs, many businesses and other organizations have initiated "wellness" programs, often with facilities at the work site to encourage exercise. Although these programs have often resulted in improved fitness for participants, weight loss has been more difficult to achieve. In this regard, in our initial study of NIH employees participating in NHLBI's Keep the Beat program--two-thirds of whom were overweight or obese--we found improved exercise fitness after 3 months of participation, with exercise averaging 20 minutes each work day, but no significant weight loss. Associated with greater fitness in our participants was improvement in endothelial function, an important biomarker of cardiovascular risk. Because level of fitness is a strong predictor of cardiovascular (and total) mortality in population studies, some investigators and thought leaders have proposed that it is acceptable to be "fat and fit." We found in our study, however, that exercise alone has little effect on insulin sensitivity and other biomarkers of risk, including C-reactive protein, which could limit further improvement in endothelial function and even greater risk reduction. We propose to test in this protocol whether weight loss through supervised nutritional counseling and daily exercise at worksite facilities confers health benefits beyond those achieved with improved fitness alone, such as improvement in endothelial function, arterial compliance, insulin sensitivity, markers of inflammation in blood and high-density lipoprotein (HDL) structure and function. Because obesity in a sedentary workforce environment is especially prevalent among women, with additional contribution of menopause to obesity, our study will be restricted to overweight and obese women to allow appropriate analysis in a cohort of manageable size for our testing resources. The primary endpoint will be differential improvement in endothelial function, as determined by brachial artery reactivity to shear stress, from baseline to 6 months in participants randomized to exercise coupled with weight-loss intervention versus subjects randomized to exercise alone. Secondary analyses will include comparisons of adiposity, arterial stiffness, insulin sensitivity, HDL subparticles and function, and markers of inflammation and adipokines in blood, with exploratory analyses of minorities and age/hormonal interactions. Demonstration of improved vascular function and other biomarkers of cardiovascular risk with improved fitness combined with weight loss may serve as an incentive for greater participation in organization-initiated wellness programs with emphasis both on exercise and on personalized nutritional counseling.