Serum androgens and risk of atrial fibrillation in older men: The Cardiovascular Health Study.

BACKGROUND: Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined.

HYPOTHESIS: Low serum androgens are associated with an increased risk of AF.

METHODS: We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men with average age 76.3 ±4.9 years in the Cardiovascular Health Study.

RESULTS: After median follow-up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT-proBNP levels, men with free DHT <0.16 ng/dL were at increased risk compared with men with higher levels (hazard ratio: 1.48, 95% confidence interval: 1.01-2.17, P <0.05). Sensitivity analyses confirmed that the increased risk was not cutpoint-specific, with a significant association noted up to cutpoints <~0.2 ng/dL. We also detected a complex nonlinear association between SHBG and incident AF, in which subjects in the middle quintile (52.9-65.3 nmol/L) had increased risk.

CONCLUSIONS: Among older men, low free DHT is associated with an increased risk of incident AF. Further studies are needed to explore mechanisms for this association.