Vitamin D and cardiovascular outcomes in multiple sclerosis

Background: Vitamin D (25(OH)D) deficiency is linked to increased cardiovascular disease (CVD) risk in the general population, but its implications for people with multiple sclerosis (pwMS) remain unexplored. This study aimed to evaluate the association of 25(OH)D with long-term CVD outcomes in pwMS and the impact of vitamin D supplementation. Methods: This observational cohort study analysed anonymised medical records from 70 healthcare organisations following pwMS for 5-years (2019–2024). PwMS and deficient or inadequate 25(OH)D levels were 1:1 propensity-score matched with pwMS and adequate 25(OH)D levels, for demographics, comorbidities, and cardiovascular care. Cox proportional hazard models analysed the incidence of all-cause mortality, stroke, acute myocardial infarction, heart failure, angina, atrial fibrillation/flutter, and a composite measure of major adverse cardiovascular events (MACE). Propensity-matched pwMS who had deficient or inadequate 25(OH)D levels taking cholecalciferol were compared to pwMS and adequate 25(OH)D levels (not taking supplementation). Results: Amongst 74,372 pwMS, 9 % had deficient 25(OH)D levels, 18 % inadequate, and 73 % adequate. Deficient, or inadequate 25(OH)D levels were associated with an increased rate of MACE (HR, 1.32 [95 % CI: 1.19, 1.46], HR, 1.29 [95 % CI: 1.20, 1.40], respectively) compared to those with adequate levels. Cholecalciferol supplementation in pwMS and deficient or inadequate 25(OH)D levels did not alleviate the higher CVD rate (HR, 1.39 [95 % CI: 1.21,1.60], HR, 1.31 [95 % CI: 1.17, 1.47], respectively) in comparison to those with adequate 25(OH)D levels taking no vitamin D supplementation. Conclusions: Deficient or inadequate 25(OH)D levels in pwMS were associated with an increased rate of MACE, which may not be mitigated by vitamin D supplementation.