Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies

Circulating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483.A total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26-1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46-2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose-response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89-0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32-0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65-0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044).The lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events.