Increased Ferritin Concentration and Risk of Atrial Fibrillation and Heart Failure in Men and Women: Three Studies of the Danish General Population Including 35799 Individuals

Moderately increased plasma ferritin, as a biomarker of iron overload, has been associated with higher rates of cardiovascular death and heart failure. However, the association of moderately increased plasma ferritin with risk of atrial fibrillation in the general population is unknown.We examined the association of plasma ferritin concentrations with risk of atrial fibrillation and heart failure in metaanalyses of 35799 men and women from 3 studies of the Danish general population: the Copenhagen City Heart Study, the Danish General Suburban Population Study, and the Copenhagen General Population Study.Multivariable adjusted fixed effects odds ratios for atrial fibrillation were 1.23 (95% CI, 1.05-1.44; P = 0.005) in men for ferritin concentration ≥300 μg/L vs <300 μg/L, 1.13 (95% CI, 0.93-1.38; P = 0.22) in women for ≥200 μg/L vs <200 μg/L, and 1.19 (95% CI, 1.06-1.35; P = 0.005) in both sexes combined (Psex interaction = 0.52). Corresponding fixed effects odds ratios for heart failure were 1.16 (95% CI, 0.98-1.37; P = 0.08) in men, 0.86 (95% CI, 0.67-1.10; P = 0.23) in women, and 1.05 (95% CI, 0.91-1.21; P = 0.45) in both sexes combined (Psex interaction = 0.05). Multivariable adjusted fixed effects odds ratio for atrial fibrillation per step increase in ferritin concentrations was 1.13 (95% CI, 1.06-1.21; Ptrend = 0.0005) in both sexes combined (Psex interaction = 0.59); the corresponding value for heart failure was 1.03 (95% CI, 0.95-1.11; Ptrend = 0.47) (Psex interaction = 0.08). In sensitivity analyses, there was no evidence of U-shaped relationships between plasma ferritin concentrations and risk of atrial fibrillation or heart failure in men or women.Increased ferritin concentration is associated with increased risk of atrial fibrillation in the general population.