Associations of Endogenous Sex Hormones with Carotid Plaque Burden and Characteristics in Midlife Women

Abstract

Abstract Context Endogenous sex hormones may be involved in the pathogenesis of cardiovascular disease (CVD) in women. Carotid plaque characteristics, such as echogenicity, an ultrasound measure that reflects plaque composition, may identify unstable plaques that are more likely to rupture, precipitating a CVD event. However, few studies have considered sex steroids in relation to carotid plaque and its characteristics. Objective To evaluate estrone (E1), estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and free T (FT) in relation to carotid plaque in women. Design, Setting, and Participants In MsHeart, a cross-sectional study of 304 women aged 40 to 60 years, participants underwent a carotid artery ultrasound assessment. The current analysis included MsHeart participants with carotid plaque (n = 141, 46%). E1, E2, and T were assayed using liquid chromatography–tandem mass spectrometry; FT was estimated using ensemble allostery models. Regression models were adjusted for sociodemographic characteristics and CVD risk factors. Main Outcomes Carotid plaque burden (number of plaques, total plaque area [TPA]) and characteristics (calcification, echogenicity) were determined using semi-automated software. Results SHBG was inversely related to TPA (odds ratio [OR] 0.39; 95% confidence interval [CI] 0.21, 0.74; multivariable) and higher FTs were associated with greater TPA (OR 2.89; 95% CI 1.31, 6.37; multivariable). Higher E1 was related to echogenicity (OR 2.31; 95% CI 1.26, 4.33; multivariable), characteristic of more stable plaque. Conclusions SHBG and FT are related to TPA while E1 is related to plaque echogenicity, suggesting these hormones have different roles in the development of carotid plaque. Our findings highlight the importance of sex hormones in the development of carotid plaque in midlife women.