Association Between Vitamin D Deficiency and the Incidence of Atrial Fibrillation: A Systematic Review and...

Background: Vitamin D has been implicated in several biological pathways involved in atrial remodeling, yet its association with incident atrial fibrillation (AF) remains uncertain across epidemiological studies. Objectives: The objective was to evaluate the association between circulating vitamin D levels and the risk of incident AF through a systematic review and meta-analysis of prospective studies using a harmonized continuous analytical framework. Methods: A systematic review and meta-analysis of prospective cohort studies was performed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using the generic inverse variance method. To improve comparability across studies, effect estimates were harmonized to a common continuous contrast corresponding to a 1-standard-deviation (1-SD) difference in circulating vitamin D levels. Estimates were then oriented such that higher values reflected lower vitamin D status and higher AF risk. Random-effects models were used as the primary analytical approach. Sensitivity analyses included leave-one-out testing and an additional pooled analysis incorporating a threshold-based study after approximate rescaling to the continuous 1-SD framework. Results: Five prospective studies were eligible for quantitative assessment. In the primary continuous harmonized analysis, including the four studies with directly reported or more reliably rescaled continuous estimates, lower vitamin D status was associated with a higher risk of incident AF (HR 1.08, 95% CI 1.05-1.11), with no statistical heterogeneity (I² = 0%). In a sensitivity analysis including the HUNT study after approximation of its threshold-based estimate to the continuous 1-SD framework, the pooled association remained statistically significant (HR 1.08, 95% CI 1.05-1.11), with low heterogeneity (I² = 7%). The direction of effect remained stable across sensitivity analyses. Conclusions: Lower circulating vitamin D levels were associated with a modestly higher risk of incident AF in prospective studies. The most internally consistent quantitative signal emerged from analyses conducted within a common continuous 1-SD framework. Inclusion of a threshold-based study through approximate rescaling did not materially alter the pooled estimate, although this step relied on additional assumptions. These findings support an observational association but do not establish causality or justify vitamin D supplementation specifically for AF prevention.