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，需要有效的预防措施。实验研究表明，维生素D和I-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I-3 FA摄入量与血压（BP）和HTN呈负相关。小型干预试验表明维生素D和富含I-3 FA的鱼油可能具有降低血压的作用；然而，使用足够高剂量的维生素D和i - 3fa进行HTN一级预防的大型试验缺乏。维生素D和OmegA-3试验（VITAL）是美国国立卫生研究院支持的一项大型、随机、双盲、安慰剂对照、2 × 2因子试验，将测试2000 IU/天的维生素D（维生素D3[胆钙化醇]）和1 g/天的海洋I-3 FA（二十碳五烯酸[EPA] +二十二碳六烯酸[DHA]）补充剂对2万名多种族男性和女性心血管疾病和癌症发病率的影响，并进行5年的治疗和随访。VITAL提供了一个最佳的成本效益设置，以检查干预措施对BP和事件HTN变化的影响。此外，由于该项目将与母体VITAL试验同时开始，因此可以对血压和生物标志物进行预随机化评估。在这项拟议的辅助研究中，我们将从美国5个主要大都市招募1000名无基线HTN的VITAL参与者，在基线时进行家庭检查，并通过检查管理服务公司（EMSI）进行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、24小时尿液和其他临床评估。我们还将在整个VITAL试验中确定意外HTN病例。我们将检验以下假设：(1)在1000名参与者的EMSI亚队列中，与安慰剂相比，维生素D和鱼油补充剂是否会降低24小时ABP；(2)与安慰剂相比，在所有没有基线HTN的随机VITAL参与者中，维生素D和鱼油补充剂是否能降低HTN发生的风险；(3)与安慰剂相比，维生素D和鱼油补充剂是否有利于改变HTN相关的生物标志物，这些生物标志物被认为是连接维生素D和I-3 FAs与HTN的机制介质。本研究将为支持或反驳维生素D和I-3 FA对BP和HTN发展的潜在预防作用提供明确证据。

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 I-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 I-3 FA intake with blood pressure (BP) and HTN. Small intervention trials of vitamin D and fish oil rich in I-3 FA suggest possible BP-lowering effects; however, larger trials using adequately high doses of vitamin D and I-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 I-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 I-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 I-3 FA on BP and the development of HTN.