Higher serum sex hormone-binding globulin levels are associated with incident cardiovascular disease in men

Abstract

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 (35-80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) cohort. The analytic sample included 1492 men without baseline (2002-2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007-2010), and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD - mortality, were analysed using logistic regression for incident CVD and Cox's 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 (OR=1.54 [1.15, 2.06] per SD increase in SHBG, p=0.003) and (OR =0.71 [0.52, 0.97] per SD decrease in TT, p=0.03), respectively. A decrease in TT between time points was associated with incident CVD (OR=0.72 [0.56, 0.92], P=0.01). Neither SHBG nor TT were significantly associated with all-age CVD mortality (HR=0.69 [0.29, 1.63], p=0.40 & HR=0.60 [0.28, 1.26], p=0.18, respectively). Conclusions: Among all men and men aged over 65, both elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.