Association of endogenous sex hormone levels with coronary artery calcium progression among post-menopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Sex differences in the incidence and manifestation of cardiovascular disease (CVD) suggest the involvement of sex hormones in disease pathogenesis. Coronary artery calcium (CAC) and its progression, measured by non-contrast cardiac computed tomography, are markers of subclinical atherosclerosis and predict CVD, even among low-risk women. We hypothesized that sex hormone levels were associated with CAC progression among women in the Multi-Ethnic Study of Atherosclerosis. We studied 2,759 post-menopausal women (age 65±9 years), free of baseline CVD, with baseline serum sex hormones and CAC measured at Exam 1 (2000–2002). Of this sample, 2,427 had ≥1 follow-up CAC measurement through Exam 5 (2010–2012). Using mixed effects linear regression methods, we tested change in log[CAC+1] score by log[sex hormone] levels (continuous, comparing the 90th versus 10th percentiles). Models adjusted for demographics, lifestyle factors, cardiovascular risk factors, hormone therapy, and years since menopause. At baseline, we found no associations between sex hormones and prevalent CAC. Over a median of 4.7 years, in fully-adjusted models, women with higher free testosterone levels had a greater relative CAC progression ratio (95% CI) [1.26 (1.011.56)], whereas higher sex hormone binding globulin (SHBG) was associated with lower progression risk [0.80 (0.64–0.99). No associations were seen for total testosterone, estradiol, or dehydroepiandrosterone. A more androgenic hormone profile of higher free testosterone and lower SHBG is associated with a greater CAC progression up to 10-years in post-menopausal women. Sex hormone levels may help identify women at increased risk for CVD who may benefit from additional risk-reducing strategies.