Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors

Objective: Recent epidemiological studies have found that testosterone deficiency is associated with higher mortality largely due to cardiovascular (CV) disease in community-dwelling older men. We investigated whether a low plasma testosterone level could predict cardiovascular events in middle-aged Japanese men with coronary risk factors. Methods: One hundred and seventy-one male outpatients (30-69 years old, mean +/- SD= 48 +/- 13 years) who had any coronary risk factor (hypertension, diabetes, dyslipidemia, smoking, and obesity) without a previous history of CV disease were followed up. At baseline, the subjects underwent examination of coronary risk factors, measurement of flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular endothelial function and assays of plasma total testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol and cortisol. Results: During the mean follow-up period of 77 months, a total of 20 CV events occurred. Kaplan-Meier survival analysis by tertile of plasma hormone levels revealed that the subjects with the lowest testosterone tertile were more likely to develop CV events than those with the highest tertile (P < 0.01 by log-rank test). Cox proportional hazards models showed that the subjects with the lowest tertile of plasma testosterone (<14.2 nmol/L) had an approximately 4-fold higher CV event risk compared to those with the higher testosterone tertiles after adjustment for coronary risk factors including medication and FMD (unadjusted hazard ratio, 3.61; 95% CI, 1.47-8.86: multivariate-adjusted hazard ratio, 4.61; 95% CI, 1.02-21.04). Multivariate analysis did not show any significant association of DHEA-S, estradiol or cortisol with CV events. Conclusions: A low plasma testosterone level is associated with CV events in middle-aged Japanese men, independent of coronary risk factors and endothelial function. This is the first report to show the relationship between endogenous testosterone and CV events in Asian population. (C) 2009 Elsevier Ireland Ltd. All rights reserved.