Clinical Trail to Reverse Early Arterial Stiffening

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DESCRIPTION (provided by applicant): Obesity and reduced physical activity have adverse vascular effects that lead to increases in blood pressure and arterial stiffness and a premature aging of the cardiovascular system. This leads eventually to chronic hypertension, heart failure and cardiovascular mortality. The metabolic effects of sodium are enhanced with obesity and thus sodium consumption likely modulates many of the vascular effects of obesity. W e hypothesize that in young adults, the vascular effects of obesity are reversible with weight reduction and increases in activity. We further hypothesize that sodium intake plays a. role in the extent to which arterial stiffness can be reduced. We propose to test these hypotheses in a clinical trial of 300 adults aged 20 to 45 who are moderately overweight (BMI 25-35). All participants will receive a dietary and activity intervention with a goal of achieving a 10% weight loss and an increase in weekly activity level of 150-200 minutes. Participants will be randomized to either a low sodium or a control sodium intake. The effect of the intervention on the cardiovascular system will be evaluated through measurement of Pulse Wave Velocity (PWV), endothelial function and common carotid will thickness and diameter. The primary trial endpoint will be aortic PWV, because this measure reflects both structural and functional vascular changes that are expected to occur with the intervention. The proposed interventions are expected to influence the vasculature through numerous mechanisms including altering adipocytokine production, insulin resistance, sympathetic activity, the RAAS, inflammation, and glucose and lipid metabolism. Measures of each of these processes have been incorporated and each will be repeated over time to provide a dynamic picture of the effects of the intervention on the vasculature. We will store samples of plasma, serum, urine and DNA to allow further testing through alternate funding mechanisms. The results of this trial will provide valuable information on the best intervention to preserve vascular health. A more thorough understanding of the mechanism linking obesity, sodium consumption and vascular health can be used to formulate targeted therapies for obesity-related vascular damage.