Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study
OBJECTIVE Testosterone (T) is assumed to be a risk factor for coronary artery disease (CAD). However, recent studies have demonstrated a beneficial effect of T on myocardial ischaemia in men with CAD. To assess the potential role of T in CAD in postmenopausal women we investigated the association between T level and CAD and relationship between T and other CAD metabolic risk factors. RESULTS Within the 12-month study period, 108 consecutive, postmenopausal women (age 62+/-7 years) referred for diagnostic coronary angiography were prospectively included in the study. In all patients serum level of T, sex hormone-binding globulin (SHBG), total cholesterol (T-chol), LDL-chol, HDL-chol, triglycerides (TG), apolipoproteins A(1) and B (apo A(1), apo B), lipoprotein a [Lp(a)], and C reactive protein were measured. Testosterone free index (TFI) was calculated as Tx100/SHBG. CAD was documented in 51 (47%) patients (CAD+). Women with CAD had decreased T level and lower TFI (T: 0.99+/-0.4 vs. 1.41+/-0.7 nmol/l, P=0.005; TFI: 3.2+/-1.4 vs. 4.2+/-2.2, P=0.04, CAD+ vs. CAD-, respectively). No difference in SHBG was found between the two groups. In 16 women (six CAD+, 10 CAD-) who were on hormonal replacement therapy (HRT+) we observed significantly elevated T level and TFI (T: 1.62+/-0.5 vs. 1.15+/-0.7 nmol/l; TFI: 5.0+/-2.2 vs. 3.5+/-1.8, HRT+ vs. HRT-, respectively, P<0.05). When these women were excluded from the analysis, T level remained decreased in CAD+ group (0.96+/-0.4 vs. 1.22+/-0.5 nmol/l, CAD+ vs. CAD- respectively, P<0.02). CAD+ group had an unfavourable profile of metabolic CAD risk factors as evidenced by elevated T-chol, LDL-chol, Lp(a), apoB, and decreased apoA(1) (P<0.05 vs. CAD- in all comparisons). Neither T nor TFI correlated with CAD metabolic risk factors (r<0.2, P>0.1 for all correlations), apart from an inverse correlation between T and Lp(a) (r=-0.24, P=0.04). CONCLUSION In postmenopausal women decreased T level is associated with CAD independently of the other CAD metabolic risk factors. Hormonal replacement therapy tends to increase T level which may further support the beneficial role of HRT in postmenopausal women.