Higher Serum Sex Hormone-Binding Globulin Levels Are Associated with Incident Cardiovascular Disease in Men

Context: Sex hormone-binding globulin (SHBG) levels are associated with cardiovascular disease (CVD) risk factors. However, prospective data on the association between SHBG levels and CVD events are sparse, with conflicting results. Objectives: To examine associations between serum SHBG, total testosterone (TT), and incident CVD and CVD-related mortality in middle-aged to elderly men. Design and Methods: Data on 2563 community-dwelling men (35 to 80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress cohort. The analytic sample included 1492 men without baseline (2002 to 2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007 to 2010) and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD mortality, were analyzed using logistic regression for incident CVD and Cox proportional hazard regression for CVD mortality, adjusting for established CVD risk factors. Results: In multivariable models, elevated baseline SHBG and lower baseline TT were independently associated with incident CVD (SHBG: OR, 1.54; 95% CI, 1.15 to 2.06 per SD increase in SHBG, P = 0.003; TT: OR, 0.71; 95% CI, 0.52 to 0.97 per SD decrease in TT; P = 0.03). A decrease in TT between time points was associated with incident CVD (OR, 0.72; 95% CI, 0.56 to 0.92; P = 0.01). Neither SHBG nor TT was significantly associated with all-age CVD mortality [hazard ratio (HR), 0.69; 95% CI, 0.29 to 1.63; P = 0.40; and HR, 0.60; 95% CI, 0.28 to 1.26; P = 0.18, respectively]. Conclusions: Among all men and men >65 years, elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.