Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study

Low-grade inflammation has been repeatedly associated with cardiovascular diseases but the relationship with incidence of atrial fibrillation (AF) remains unclear. We explored the association between elevated plasma levels of inflammation-sensitive proteins (ISPs) and incidence of AF in a population-based cohort. Plasma levels of five ISPs (fibrinogen, haptoglobin, ceruloplasmin, alpha(1)-antitrypsin and orosomucoid) and two complement factors (C3 and C4) were measured in 6,031 men (mean age 46.8 years) without history of myocardial infarction, heart failure, stroke or cancer. Incidence of hospitalizations due to AF during a mean follow-up of 25 years was studied both in relation to individual inflammatory proteins and the number of elevated ISPs. During follow-up, 667 patients were hospitalized with a diagnosis of AF. After adjustment for potential confounding factors, the hazard ratios (HR) for AF were 1.00 (reference), 1.08 (95% CI: 0.88-1.31), 1.07 (CI: 0.84-1.36), and 1.40 (CI: 1.12-1.74), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (P for trend = 0.007). Ceruloplasmin was the only individual ISP significantly associated with incidence of AF after adjustment for confounding factors (HR 1.17 per standard deviation, 95% CI: 1.08-1.26). In conclusion, a score of five ISPs was associated with long-term incidence of hospitalizations due to AF in middle-aged men. Of the individual ISPs, a significant association was observed for ceruloplasmin, a protein previously associated with copper metabolism and oxidative stress.