Is Circulating Vitamin D Status Associated with the Risk of Venous Thromboembolism? A Meta-Analysis of Observational Studies

Background: Although vitamin D is antithrombotic, associations between serum vitamin D status and the risk of venous thromboembolism (VTE) remain inconsistent. Methods: We searched the EMBASE, MEDLINE, Cochrane Library, and Google Scholar databases from inception to June 2022 to identify observational studies examining associations between vitamin D status and VTE risk in adults. The primary outcome presented as odds ratio (OR) or hazard ratio (HR) was the association of vitamin D levels with the risk of VTE. Secondary outcomes included the impacts of vitamin D status (i.e., deficiency or insufficiency), study design, and the presence of neurological diseases on the associations. Results: Pooled evidence from a meta-analysis of sixteen observational studies, including 47648 individuals published from 2013 to 2021, revealed a negative relationship between vitamin D levels and the risk of VTE either based on OR (1.74, 95% confidence interval (CI): 1.37 to 2.20, p < 0.00001; I(2) = 31%, 14 studies, 16074 individuals) or HR (1.25, 95% CI: 1.07 to 1.46, p = 0.006; I(2) = 0%, 3 studies, 37,564 individuals). This association remained significant in subgroup analyses of the study design and in the presence of neurological diseases. Compared to individuals with normal vitamin D status, an increased risk of VTE was noted in those with vitamin D deficiency (OR = 2.03, 95% CI: 1.33 to 3.11) but not with vitamin D insufficiency. Conclusions: This meta-analysis demonstrated a negative association between serum vitamin D status and the risk of VTE. Further studies are required to investigate the potential beneficial effect of vitamin D supplementation on the long-term risk of VTE.