Clinical Trail to Reverse Early Arterial Stiffening

描述（由申请人提供）：肥胖和体力活动减少会对血管产生不利影响，导致血压和动脉僵硬度升高以及心血管系统过早衰老。这最终会导致慢性高血压、心力衰竭和心血管疾病死亡。钠的代谢作用随着肥胖而增强，因此钠的消耗可能会调节肥胖对血管的许多影响。我们假设，在年轻人中，肥胖对血管的影响随着体重减轻和运动增加是可逆的。我们进一步假设钠摄入量在动脉僵硬程度上起作用。我们建议对300名年龄在20至45岁的中度超重（BMI 25-35）的成年人进行临床试验，以检验这些假设。所有参与者都将接受饮食和活动干预，目标是体重减轻10%，每周活动时间增加150-200分钟。参与者将被随机分为低钠组和控制钠摄入量组。通过测量脉搏波速度（PWV）、内皮功能和颈总动脉厚度和直径来评估干预对心血管系统的影响。主要试验终点将是主动脉PWV，因为这一指标反映了干预后血管结构和功能的变化。建议的干预措施有望通过多种机制影响血管系统，包括改变脂肪细胞因子的产生、胰岛素抵抗、交感神经活动、RAAS、炎症和糖脂代谢。这些过程的每一个措施都被纳入其中，每一个都将随着时间的推移而重复，以提供干预对脉管系统影响的动态图像。我们将储存血浆、血清、尿液和DNA样本，以便通过其他供资机制进行进一步检测。这项试验的结果将为维护血管健康的最佳干预提供有价值的信息。更深入地了解肥胖、钠摄入和血管健康之间的联系机制，可以用于制定针对肥胖相关血管损伤的靶向治疗。

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.