Clinical Trail to Reverse Early Arterial Stiffening

描述(申请人提供)：肥胖和体力活动减少会对血管产生不良影响，导致血压升高和动脉僵硬，并导致心血管系统过早老化。这最终会导致慢性高血压、心力衰竭和心血管死亡。钠的代谢效应随着肥胖而增强，因此钠的摄入可能调节肥胖的许多血管效应。我们假设，在年轻人中，肥胖的血管效应是可逆的，随着体重的减轻和活动量的增加。我们进一步假设钠摄入量在降低动脉僵硬的程度上起作用。我们建议对300名年龄在20岁至45岁、中度超重(BMI 25至35)的成年人进行临床试验，以检验这些假说。所有参与者都将接受饮食和活动干预，目标是实现10%的体重减轻和每周150-200分钟的活动水平增加。参与者将被随机分为低钠组和控制组。通过测量脉搏波速度(PWV)、血管内皮功能及颈总动脉厚度和直径来评价干预对心血管系统的影响。主要试验终点将是主动脉PWV，因为这一测量反映了预期在介入治疗中发生的结构和功能血管变化。预计拟议的干预措施将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、交感活性、RAAS、炎症以及糖脂代谢。这些过程中的每一项措施都已纳入其中，每一项措施都将随着时间的推移而重复，以提供干预对血管系统影响的动态图景。我们将储存血浆、血清、尿液和DNA样本，以便通过替代资金机制进行进一步检测。这项试验的结果将为保护血管健康的最佳干预措施提供有价值的信息。更透彻地了解肥胖、钠摄入量和血管健康之间的联系机制，可以用来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.