Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis

Abstract

Background: Low 25-hydroxyvitamin D status has been associated with increased cardiovascular events in epidemiologic studies.

Objective: We assessed whether vitamin D supplementation reduces cardiac failure, myocardial infarction (MI), and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta-analysis.

Design: Two analyses were undertaken. The first analysis was a trial analysis. The RECORD was a factorial RCT that compared vitamin D₃ (800 IU/d), calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by using Cox regression. The second analysis was a systematic review. MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and participants mean or median age ≥60 y were included. Meta-analyses were based on a Bayesian fixed-effects model by using a complementary log-log link function to account for varying lengths of follow-up.

Results: In the trial analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively. Twenty-one studies met the inclusion criteria for the systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D compared with the placebo or control for on-study events for cardiac failure, MI, and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.

Conclusion: Vitamin D supplementation might protect against cardiac failure in older people but does not appear to protect against MI or stroke.