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

Aims: 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 25hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and nonfatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483. Data synthesis: 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). Conclusions: The lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events. (c) 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Automated summary

The circulating level of vitamin D is associated with the risk of cardiovascular disease, with lower levels of 25(OH)D being linked to increased risk of both CVD incidence and recurrent events. An inverse linear association was found between 25(OH)D levels and non-fatal CVD incidence events, while a non-linear association was observed with fatal and combined CVD events.