Investigating the relationship between serum vitamin D levels over time and the incidence of atrial fibrillation in The HUNT Study

Background and Aims Evidence of the association between serum vitamin D levels and atrial fibrillation (AF) is inconclusive. Thus, this study investigated the relationship between long-term average serum 25-hydroxyvitamin D (25(OH)D) levels and AF incidence in the Norwegian Trøndelag Health (HUNT) Study using a prospective cohort design and a Mendelian randomization (MR) approach. Methods A total of 3394 adults with two measurements of serum 25(OH)D at HUNT2 (1995-1997) and HUNT3 (2006-2008) and without AF at HUNT3 were followed up to 2021. Average serum 25(OH)D levels over ten years were categorized into <50 and ≥50 nmol/L. AF diagnoses were retrieved from hospital registers and validated by doctors. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Furthermore, a one-sample MR was conducted among 36,554 adults who participated in both HUNT2 and HUNT3 using the Wald ratio method. Results During a median 12-year follow-up, 304 AF cases were diagnosed. Serum 25(OH)D levels <50.0 nmol/L were associated with a 27% reduced incidence of AF (HR 0.73, 95% CI 0.57 to 0.93) compared with ≥50 nmol/L after adjustment for confounders. A genetically determined 10 nmol/L decrease in the serum 25(OH)D levels was associated with a 7% reduced incidence of AF (HR 0.93, 95% CI 0.86 to 1.00) in the one-sample MR. Sensitivity analyses supported this association. Conclusions Using both traditional observational and one-sample MR approaches, the study suggested a consistently positive association between long-term average serum 25(OH)D levels and incidence of AF in the Norwegian HUNT population.