Combination of low free testosterone and low vitamin D predicts mortality in older men referred for coronary angiography

Abstract

Summary: Context: Low levels of 25‐hydroxyvitamin D [25(OH)D] and free testosterone (FT) are both associated with increased mortality. Experimental studies show a complex interplay of vitamin D and androgen metabolism suggesting that a deficiency of both hormones may be associated with a particularly adverse clinical outcome. Objective: To evaluate the impact of parallel FT and 25(OH)D deficiency in a large cohort of older men. Design: We measured total testosterone (TT), sex hormone‐binding globulin and 25(OH)D levels in 2069 men who were routinely referred for coronary angiography (1997–2000). Main outcome measures: Cox proportional hazard ratios (HR s) (with 95% confidence intervals) for mortality from all causes, cardiovascular and noncardiovascular causes according to combined deficiency of FT and 25(OH)D. Results: In multivariate‐adjusted analyses, we found an increased risk for all‐cause mortality, cardiovascular and noncardiovascular mortality for men in the lowest FT [HR 1·26 (1·03–1·54), 1·24 (0·96–1·60) and 1·39 (1·00–1·93), respectively] and 25(OH)D quartile [HR 1·77 (1·47–2·13), 1·65 (1·29–2·10) and 1·89 (1·38–2·60) respectively] compared with men in higher FT and 25(OH)D quartiles. There was no independent association of TT levels with mortality. Multivariate‐adjusted HR s progressively increased with the number of hormones (FT and 25(OH)D) in the lowest quartile [0 vs 2 hormone deficiencies: 2·11 (1·60–2·79) for all cause, 1·77 (1·23–2·55) for cardiovascular and 2·33 (1·45–3·47) for noncardiovascular mortality, respectively]. Conclusion: A combined deficiency of FT and 25(OH)D is significantly associated with fatal events in a large cohort of men referred for coronary angiography.