Low testosterone levels are predictive for incident atrial fibrillation and ischaemic stroke in men, but protective in women – results from the FINRISK study

Abstract

Background Atrial fibrillation is the most common serious abnormal heart rhythm, and a frequent cause of ischaemic stroke. Recent experimental studies, mainly in orchiectomised rats, report a relationship between sex hormones and atrial electrophysiology and electroanatomy. We aimed to evaluate whether low testosterone levels are predictive for atrial fibrillation and/or ischaemic stroke in men and women. Design and methods The serum total testosterone levels were measured at baseline in a population cohort of 7892 subjects (3876 male, 4016 female), aged 25-74 years, using a commercially available immunoassay. The main outcome measure was atrial fibrillation or ischaemic stroke, whichever came first. Results During a median follow-up of 13.8 years, a total of 629 subjects (8.0%) suffered from incident atrial fibrillation ( n = 426) and/or ischemic stroke ( n = 276). Cox regression analyses, adjusted for age (used as time-scale), geographical region, total cholesterol (log), high-density lipoprotein-cholesterol (log), hypertension medication, known diabetes, smoking status, waist-hip-ratio, and time of blood drawn, documented differential predictive value of low sex-specific testosterone levels for atrial fibrillation and/or ischaemic stroke, in men and in women: Increasing levels were associated with lower risk in men (hazard ratio per one nmol/l increase 0.98 (95% confidence interval 0.93-1.00); p = 0.049). On the other hand, increasing testosterone levels were associated with higher risk in women (hazard ratio per one nmol/l increase 1.17 (95% confidence interval 1.02-1.36); p = 0.031). Conclusion Our study indicates that low testosterone levels are associated with increased risk of future atrial fibrillation and/or ischaemic stroke in men, while they are protective in women.

Predictive value of low testosterone concentrations regarding coronary heart disease and mortality in men and women – evidence from the FINRISK97 study

“…By its strict methodological approach and its prospective design with long‐term follow‐up of almost 14 years and large sample size, as well as the inclusion of women, our study delivers very strong evidence on the irrelevance of low testosterone levels regarding future CHD risk and mortality. These results seem surprising in view of two previous reports of the FINRISK97 study, linking low testosterone levels to incident diabetes and also atrial fibrillation and subsequent stroke in men . However, in contrast to CHD, for both entities, distinct testosterone‐based pathomechanisms are well understood.…”

Vascular Pathways of Testosterone: Clinical Implications

“…Recent evidence confirms that low T levels are a risk factor not only for ischemic stroke but also for AF [142,143]. An independent association between lone AF and low levels of T was reported [144], suggesting that T may be protective for the regulation of myocardial electrical conduction.…”

Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table

“…Gender differences in stroke are incompletely understood, low testosterone levels have been observed with increased risk of AF and hence ischaemic stroke in men but not in women. 8 It is acknowledged that implementation of primary Table 1. Priorities for cardiovascular research in stroke.…”