Endogenous Testosterone and its Relationship to Preclinical and Clinical Measures of Cardiovascular Disease in the Atherosclerosis Risk in Communities Study

Abstract

Context: Epidemiologic studies suggest that endogenous testosterone (T) levels in males may be implicated in cardiovascular disease (CVD), however further clarification is needed. Objective: We assessed the cross-sectional relationship between endogenous plasma T and mean carotid intima media thickness (cIMT), and the longitudinal relationship with incident clinical CVD events, cardiac mortality, and all-cause mortality using male participants in the Atherosclerosis Risk in Communities (ARIC) study. Design: This study involved a subset of men from visit 4 of the ARIC study. Setting: The study was conducted in a community based cohort. Participants: Males who provided a morning blood sample excluding those taking androgen therapy, with prevalent coronary heart disease (CHD), stroke, or heart failure (HF) (n = 1558). Intervention: None. Main Outcome Measures: Plasma T by liquid chromatography mass spectrometry and carotid IMT using high resolution B-mode ultrasound were obtained at visit 4. Incident CHD, HF, cardiac mortality, and all-cause mortality were identified by surveillance through 2010 (median 12.8 years). Results: Lower T was significantly associated with higher body mass index, greater waist circumference, diabetes, hypertension, lower HDL, and never smoking (P = 0.01). T was not associated with mean cIMT in unadjusted or adjusted analyses. Following multivariable adjustment, there was no association of quartile (Q) of T with incident CHD [hazard ratio (HR) = 0.87 (95% CI = 0.60–1.26) for Q1; 0.97 (95% CI = 0.69–1.38) for Q2; 0.97 (95% CI = 0.69–1.36) for Q3 compared to reference of Q4] or for incident HF [HR = 0.77 (95% CI = 0.46–1.29) for Q1; 0.72 (95% CI = 0.43–1.21) for Q2; 0.87 (95% CI = 0.53–1.42) for Q3 compared to reference of Q4]. Similarly there was no association of Q of T with mortality or cardiac-associated mortality. Conclusions: Low male plasma T is cross-sectionally associated with key CVD risk factors, but after adjustment there was no association with mean cIMT, incident cardiac events, or mortality. Our results are reassuring that neither high nor low T levels directly predict atherosclerosis, but are a marker for other cardiovascular risk factors.