Impact of Vitamin D Deficiency on Subclinical Carotid Atherosclerosis: A Pooled Analysis of Cohort Studies

Context: Vitamin D-deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective: To perform a meta-analysis of studies evaluating the impact of vitamin Ddeficiency on common carotid artery IMT (CCA-IMT) and prevalence of carotid plaques. Data Sources: Studies were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Results: Twenty-one studies (3777 vitamin D-deficiency patients and 4792 controls) with data on CCA-IMT and six studies (1889 vitamin D-deficiency patients and 2883 controls) on the prevalence of carotid plaques were included. Compared with controls, vitamin D-deficiency patients showed a significantly higher CCA-IMT [mean difference (MD): 0.043 mm; 95% confidence interval (CI): 0.030, 0.056; P < 0.001] and an increased prevalence of carotid plaques [odds ratio (OR): 2.29; 95% CI: 1.03 to 5.11; P = 0.043] with an attributable risk of 35.9%. Selecting studies specifically including patients with diabetes, the prevalence of carotid plaques resulted higher in vitamin D-deficiency patients than in controls (OR: 3.27; 95% CI: 1.62 to 6.62; P = 0.001). A significant difference in CCA-IMT was confirmed when comparing patients with vitamin D insufficiency with controls (MD: 0.011; 95% CI: 0.010 to 0.012; P < 0.001). Sensitivity analyses substantially confirmed results, and regression models showed that with the exception of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and the prevalence of hypercholesterolemia, all of the other clinical and demographic covariates significantly impacted on the difference in CCA-IMT between vitamin D-deficiency patients and controls. Conclusions: Both vitamin D deficiency and vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.