澳大利亚QIMR伯格霍夫医学研究所Rachel E Neale课题组研究了补充维生素D与降低重大心血管事件风险的相关性。这一研究成果发表在2023年6月28日出版的《英国医学杂志》上。

为了研究每月向老年人补充维生素D是否会改变重大心血管事件的发生率，2014年至2020年，研究组在澳大利亚进行了一项关于每月维生素D的随机双盲安慰剂对照试验（D-健康试验）。使用计算机生成的排列块随机化来分配治疗。共招募了21315名参与者，年龄在60-84岁之间。排除标准为自我报告的高钙血症、甲状旁腺功能亢进、肾结石、骨软化症、结节病、每天补充维生素D超过500 IU，或因语言或认知障碍而无法给予同意。

干预措施为口服60000 IU/月的维生素D3（n=10662）或安慰剂（n=10653）长达五年。16882名参与者完成了干预期：安慰剂组8270名（77.6%）；维生素D组8552名（80.2%）。该分析的主要结局是通过与管理数据集的链接确定的重大心血管事件的发生，包括心肌梗死、中风和冠状动脉血运重建。每个事件作为次要结局分别进行分析。使用灵活的参数生存模型来估计风险比和95%置信区间。

21302人被纳入分析。干预中位数为五年。1336名参与者经历了重大心血管事件，其中安慰剂组699名（6.6%）；维生素D组637（6.0%）。维生素D组的重大心血管事件发生率低于安慰剂组（危险比为0.91），尤其是在基线时服用心血管药物的患者中（0.84；交互作用的P=0.12），尽管交互作用的P值不显著（<0.05）。总体而言，五年内标准化病因特异性累积发病率的差异为每1000名参与者5.8次事件，导致需要治疗172人以避免发生一次重大心血管事件。维生素D组的心肌梗死发生率（危险比为0.81）和冠状动脉血运重建率（0.89）较低，但脑卒中发生率没有差异（0.99）。

研究结果表明，补充维生素D可能会降低重大心血管事件的发生率，尽管绝对风险差异很小，置信区间与零发现一致。这些发现可能会促使人们进一步评估补充维生素D的作用，特别是在服用预防或治疗心血管疾病药物的人群中。

附：英文原文

Title: Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial

Author: Bridie Thompson, Mary Waterhouse, Dallas R English, Donald S McLeod, Bruce K Armstrong, Catherine Baxter, Briony Duarte Romero, Peter R Ebeling, Gunter Hartel, Michael G Kimlin, Sabbir T Rahman, Jolieke C van der Pols, Alison J Venn, Penelope M Webb, David C Whiteman, Rachel E Neale

Issue&Volume: 2023/06/28

Abstract:

Objective To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events.

Design Randomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments.

Setting Australia from 2014 to 2020.

Participants 21315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment.

Intervention 60000 IU/month vitamin D3 (n=10662) or placebo (n=10653) taken orally for up to five years. 16882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%).

Main outcome measures The main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals.

Results 21302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was 5.8 events per 1000 participants (95% confidence interval 12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23).

Conclusions Vitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease.

DOI: 10.1136/bmj-2023-075230

Source: https://www.bmj.com/content/381/bmj-2023-075230