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Abstract
Objective: Androgen deficiency confers an independent risk for cardiovascular events and total mortality. Hypertension, a major contributory factor to the development of cardiovascular disease, has also been associated with increased prevalence of low testosterone. We investigated whether low androgen concentration predicts major adverse cardiovascular events (MACE) in middle-aged hypertensive patients without clinical atherosclerosis. Methods: MACE in relation to total testosterone (TT) were analyzed with proportional hazards models in 228 patients (mean age 56 years). Results: During a mean follow-up of 44 months, 19/228 participants (8.3%) experienced a MACE. Compared to patients who did not experience MACE, hypertensive subjects who developed MACE had lower TT concentration (3.9±0.7 ng/ml vs 4.6±1.5 ng/ml, P<0.01) and a higher prevalence of hypogonadism (36% versus 16%, P=0.025). The study population was divided into tertiles according to the TT levels (low tertile 4.9 ng/ml). TT concentration was associated with MACE and the differences between the tertiles were significant (Mantel log-rank test: 8.372; p<0.01). Subjects in the lowest TT tertile (<4.0 ng/ml) had a threefold higher risk of MACE compared to those in the highest tertile (>4.9 ng/ml, adjusted HR 3.14, P=0.035). A TT plasma level of 5.04 ng/ml was associated with a negative predictive value (ability to “rule out” MACE) of 97.2 %. Addition of TT to standard risk factors model yielded correct patient reclassification to higher or lower risk category by 38.8 % (P=0.033). Conclusion: Our results show that plasma testosterone is associated with increased risk for a MACE in hypertensive patients. Low endogenous androgen concentration improves risk prediction when added to standard risk factors and may represent a valuable biomarker of prediction of cardiovascular disease risk in these patients.
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