Effect of Vitamin D and Omega-3 Fatty Acids on Blood Pressure and Hypertension

描述(申请人提供)：高血压(HTN)的死亡人数惊人，需要采取有效的预防措施。实验研究提示维生素D和ω-3脂肪酸(FA)水平不足可能通过多种生物学机制参与HTN的发病。观察性研究表明，血浆25-羟基维生素D(25[OH]D)水平和膳食ω-3脂肪酸摄入量与血压(BP)和HTN呈负相关。对维生素D和富含ω-3FA的鱼油进行的小型干预试验表明，可能有降血压作用；然而，缺乏使用足够高剂量的维生素D和ω-3FA作为HTN一级预防的较大试验。维生素D和omega-3试验(VITAL)是一项由美国国立卫生研究院支持的大型、随机、双盲、安慰剂对照、2x2因子试验，将测试每天服用2000IU维生素D(维生素D3[胆钙化醇])和每天1g海洋ω-3脂肪酸(二十碳五烯酸+二十二碳六烯酸)补充剂对20,000名多民族男性和女性心血管疾病和癌症的影响，并进行5年的治疗和随访。VITAL提供了最佳成本效益设置，以检查这两种干预措施对BP和突发事件HTN变化的影响。此外，由于该项目将与家长VITAL试验的登记同步开始，BP和生物标记物的预随机化评估将是可能的。在这项拟议的辅助研究中，我们将从美国5个主要大都市地区招募1,000名无基线HTN的有代表性的重要参与者，通过考试管理服务公司(EMSI)进行基线家庭检查和2年随访。我们将在这个EMSI亚队列中获得24小时动态血压(ABP)、空腹血、24小时尿量和其他临床评估。我们还将在整个重要审判中确定HTN事件。我们将检验以下假设：(1)在1,000名参与者的EMSI子队列中，补充维生素D和鱼油是否比安慰剂降低24小时的平均动脉压；(2)在所有没有HTN基线的随机重要参与者中，补充维生素D和鱼油是否比安慰剂降低发生HTN的风险；以及(3)与安慰剂相比，补充维生素D和鱼油是否有利于改变与HTN相关的生物标志物，这些生物标志物可能是将维生素D和ω-3脂肪酸与HTN联系在一起的机械性介质。这项拟议的研究将为支持或驳斥维生素D和ω-3FA对BP和HTN发展的潜在预防作用提供确凿的证据。

DESCRIPTION (provided by applicant): The human toll of hypertension (HTN) is staggering, and effective preventive measures are needed. Experimental studies suggest that inadequate vitamin D and ω-3 fatty acid (FA) levels may be involved in the pathogenesis of HTN through multiple biological mechanisms. Observational studies have shown inverse associations of plasma 25-hydroxyvitamin D (25[OH]D) levels and dietary ω-3 FA intake with blood pressure (BP) and HTN. Small intervention trials of vitamin D and fish oil rich in ω-3 FA suggest possible BP-lowering effects; however, larger trials using adequately high doses of vitamin D and ω-3 FA for the primary prevention of HTN are lacking. The VITamin D and OmegA-3 TriaL (VITAL), an NIH-supported, large, randomized, double-blind, placebo-controlled, 2x2 factorial trial, will test 2000 IU/day of vitamin D (as vitamin D3 [cholecalciferol]) and 1 g/day of marine ω-3 FA (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements on incident cardiovascular disease and cancer in 20,000 multiethnic men and women with 5 years of treatment and follow-up. VITAL provides an optimal cost-effective setting to examine the effects of both interventions on changes in BP and incident HTN. Further, as this project would begin in parallel with enrollment into the parent VITAL trial, pre-randomization assessments of BP and biomarkers will be possible. In this proposed ancillary study, we will recruit a representative subcohort of 1,000 VITAL participants without baseline HTN from 5 major US metropolitan areas to conduct home-based examinations at baseline and 2 years follow-up through Examination Management Services, Inc (EMSI). We will obtain 24-hour ambulatory BP (ABP), fasting bloods, 24-hour urines, and other clinical assessments in this EMSI subcohort. We will also ascertain incident HTN cases in the overall VITAL trial. We will test the following hypotheses: (1) whether vitamin D and fish oil supplementation lowers 24-hour ABP compared to placebo in the EMSI subcohort of 1,000 participants; (2) whether vitamin D and fish oil supplementation reduces the risk of incident HTN compared to placebo among all randomized VITAL participants without baseline HTN; and (3) whether vitamin D and fish oil supplementation favorably changes HTN-related biomarkers that are putative mechanistic mediators linking vitamin D and ω-3 FAs with HTN compared to placebo. This proposed study will provide definitive evidence to support or refute the potential preventive roles of vitamin D and ω-3 FA on BP and the development of HTN.