Circulating Vitamin D Level and Risk of Sudden Cardiac Death and Cardiovascular Mortality: A Dose-Response Meta-Analysis of Prospective Studies

Background: We conducted a comprehensive meta-analysis of prospective cohort studies to analyze the effect of circulating vitamin D level on the risk of sudden cardiac death (SCD) and cardiovascular disease (CVD) mortality.Methods: Prospective cohort studies evaluating the association between circulating vitamin D and risk of SCD and CVD mortality were systematically searched in the PubMed and Embase. Extracted data were analyzed using a random effects model and results were expressed in terms of hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to estimate the dose-response relationships.Results: Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating vitamin D level was 1.75 (1.49-2.06) with I2 value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43-2.38) and the clinical endpoint of SCD (pooled HRs, 2.68; 95% CI, 1.48-4.83). The dose-response analysis at the reference level of < 50 nmol/L showed a significant negative association between circulating vitamin D and risk of SCD and CVD mortality.Conclusion: Our meta-analysis of prospective cohort studies showed that lower circulating vitamin D level significantly increased the risk of SCD and CVD mortality.