A Mechanistic Trial of Dietary Sodium Reduction on Vascular Structure and Function in African Americans

项目摘要 饮食中高钠摄入量增加心血管疾病(CVD)的风险独立于既定风险 因素，包括血压(BP)。心血管疾病风险增加的非BP介导机制 与饮食钠摄入量有关的研究还不是很清楚，但观察性研究表明，直接靶点是 心脏和血管系统的器官损伤可能起到重要作用。几乎没有证据存在于 关于饮食减钠对靶器官影响的随机对照试验(RCT)，以及国家 医学科学院建议进行未来的研究，以测试不同钠摄入量水平对 为了更好地刻画钠摄入量与血管内皮功能的关系 和慢性病“。此外，还没有RCT被提供动力来测试饮食中钠的减少对 对饮食更敏感的非裔美国人的亚临床心血管结构和功能 钠的摄入量和心血管疾病的风险更高。拟议的机械性审判的总体目标是测试 低钠饮食对心脏和血管结构和功能的影响。具体地说，建议的 试验将测试饮食中钠的减少(目标是每天2,300毫克的饮食钠摄入量)是否会 改善左心室重量指数(LVMI)、左心室整体纵向应变(LVGLS)、颈动脉-股动脉 脉搏波速度(CfPWV)和血流介导的扩张(FMD)与通常摄入量的比较。此外，我们还将 测试这一效应是否独立于降血压。我们将招募240名非洲裔美国人 来自大新奥尔良地区的血压或高血压，并随机将他们分配给营养师领导的行为 干预旨在将膳食钠摄入量减少到每天2300毫克，持续12个月或降至正常饮食。 研究结果，包括心脏磁共振成像(CMR)确定的LVMI和LVGLS，cfPWV， 和FMD，将在基线、6个月和12个月的诊所就诊时使用标准化方案进行测量， 严格的质量控制。这些结果是靶器官损害的有效生物标志物，并预测 临床心血管事件的风险。在初步分析中，减钠对各亚临床脑血管病的影响 减钠组和正常饮食组之间的终点将根据意图- 治疗原则，不调整协变量。在二次分析中，动态和临床血压的变化 将进行调整，以评估饮食减少钠对每个亚临床心血管疾病的非BP依赖性影响 终结点。建议的试验具有85%的统计能力来检测在临床上显著的变化 12岁以上的四个共同原发结局(左心室心肌梗死10g/m2、左冠状动脉左前降支1.3%、左前降支0.9m/m~2、前降支1.1%) 两组间两组间差异有统计学意义(0.0125.0 5/4)。这项研究是第一个关于 测试饮食钠减少对非裔美国人亚临床心血管疾病终点的影响。调查结果来自 这项试验将填补关于饮食钠摄入量对心血管疾病风险和 为减少钠盐预防心血管疾病提供进一步的证据。

Project Summary High dietary sodium intake increases risk of cardiovascular disease (CVD) independent of established risk factors, including blood pressure (BP). Non-BP mediated mechanisms underlying the increased risk of CVD associated with dietary sodium intake are not well understood, but observational studies suggest direct target organ damage in the heart and vasculature might play an important role. Little evidence exists from randomized controlled trials (RCTs) on target organ effects of dietary sodium reduction, and the National Academy of Medicine has recommended future research to “test the effects of different sodium intake levels on endothelial and vascular function” in order to “to better characterize the relationship between sodium intake and chronic disease”. Further, no RCTs have been powered to test the effect of dietary sodium reduction on subclinical cardiovascular structure and function in African Americans, who are more sensitive to dietary sodium intake and at higher risk for CVD. The overall objective of the proposed mechanistic trial is to test the effect of dietary sodium reduction on cardiac and vascular structure and function. Specifically, the proposed trial will test whether dietary sodium reduction (targeting a dietary sodium intake of <2,300 mg/day) will improve left ventricular mass index (LVMI), left ventricular global longitudinal strain (LVGLS), carotid-femoral pulse wave velocity (cfPWV), and flow-mediated dilation (FMD) compared to usual intake. Additionally, we will test whether this effect is independent from BP reduction. We will recruit 240 African Americans with elevated BP or hypertension from the greater New Orleans area and randomly assign them to a dietitian-led behavioral intervention aimed at decreasing dietary sodium intake to <2,300 mg/day for 12 months or to a usual diet. Study outcomes, including cardiac magnetic resonance imaging (CMR)-determined LVMI and LVGLS, cfPWV, and FMD, will be measured at baseline, 6-month, and 12-month clinic visits using standardized protocols with stringent quality control. These outcomes are validated biomarkers for target organ damage and predict the risk of clinical CVD events. In primary analyses, the effect of sodium reduction on each subclinical CVD endpoint will be compared between the sodium reduction and usual diet groups according to the intention-to- treat principle without adjusting for covariates. In secondary analyses, changes in ambulatory and clinical BP will be adjusted to assess the BP-independent effect of dietary sodium reduction on each subclinical CVD endpoint. The proposed trial has 85% statistical power to detect a clinically significant difference in changes of the four co-primary outcomes (10 g/m2 in LVMI, 1.3% in LVGLS, 0.9 m/s in cfPWV, and 1.1% in FMD) over 12 months between the two groups at a 2-sided significance level of 0.0125 (0.05/4). This study is the first RCT to test the effect of dietary sodium reduction on subclinical CVD endpoints in African Americans. Findings from this trial will fill the knowledge gap of the underlying mechanisms of dietary sodium intake on CVD risk and provide further evidence on sodium reduction for CVD prevention.