Sex hormones and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA)

Atrial fibrillation is more prevalent in men than women. Due to these sex differences in atrial fibrillation susceptibility, we examined whether sex hormones have differing associations with atrial fibrillation risk in men and women. This analysis included 4883 (mean age = 63 +/- 10 years; 39% women; 64% non-white) participants from the Multi-Ethnic Study of Atherosclerosis. Sex hormones (total testosterone, bioavailable testosterone, estradiol, and sex hormone binding globulin) were measured at baseline (2000-2002) for all male and all postmenopausal female participants. Atrial fibrillation was ascertained by hospital discharge records, Medicare claims data, and study electrocardiograms through December 31, 2012. Over a median follow-up of 10.9 years, a total of 613 (13%) atrial fibrillation cases were detected. A higher incidence rate of atrial fibrillation was observed for males (n = 385, age-standardized incidence rate per 1000 person-years = 12.3, 95%CI = 11.1, 13.6) than females (n = 228, age-standardized incidence rate per 1000 person-years = 9.0, 95%CI = 7.9, 10.3). In men, higher bioavailable testosterone levels were associated with increased atrial fibrillation risk (HR = 1.32, 95%CI = 1.01, 1.74; p = 0.044; comparing 3rd to 1st tertile), while an association in the opposite direction was observed for women (HR = 0.81, 95%CI = 0.58, 1.13; p = 0.22; comparing 3rd to 1st tertile). Other hormones were not associated with atrial fibrillation in men or women. Higher levels of endogenous bioavailable testosterone contribute to atrial fibrillation development in men. The combination of endogenous bioavailable testosterone and other risk factors potentially are important for atrial fibrillation development in men.