Multi-Ethnic Study of Atherosclerosis (MESA) Association of Sex Hormones With Carotid Artery Distensibility in Men and Postmenopausal Women Multi-Ethnic Study of Atherosclerosis Dhananjay Vaidya, Sherita H. Golden, Nowreen Haq, Susan R. Heckbert, Kiang Liu, Pamela Ouyang Abstract—The decline in carotid distensibility with age is steeper in women than in men, however, the correlates of this sex difference are not known. We examined the association of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone–binding globulin, in 2783 postmenopausal women and 2987 men aged 45 to 84 years at the MultiEthnic Study of Atherosclerosis baseline examination. Carotid artery lumen diameters by ultrasound and brachial artery blood pressures were measured at systole and diastole. Regression models to determine the association of carotid distensibility coefficient and lumen diameter with sex-specific quartiles of sex hormones were adjusted for age, race, height, weight, diabetes mellitus, current smoking, antihypertensive medication use, total and high-density lipoprotein cholesterol levels, and hormone replacement therapy in women. A higher DC indicates a more distensible vessel. In women, higher dehydroepiandrosterone (P=0.008) and lower sex hormone–binding globulin (P=0.039) were associated with lower distensibility; higher dehydroepiandrosterone and lower estradiol were associated with smaller carotid diameters. In men, higher Bio-T (P=0.009) and lower estradiol (P=0.007) were associated with greater distensibility and also with smaller diameters (P=0.012 and 0.002, respectively). An androgenic internal milieu is associated with lesser carotid distensibility and diameter remodeling in women, but the opposite is true for men. Higher levels of estradiol are associated with smaller carotid diameters in both the sexes. Future longitudinal and experimental studies are needed to reveal the mechanism and clinical consequences of these associations. (Hypertension. 2015;65:1020-1025. DOI: 10.1161/HYPERTENSIONAHA.114.04826.) Online Data Supplement
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Key Words: aging
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lder age is more strongly associated with lower carotid distensibility in women as compared with men aged 45 to 84 years (2.52×10−5 versus 2.16×10−5/mm Hg lower distensibility coefficient [DC] per year of age; P=0.006).1 One SD lower carotid artery distensibility is associated with a 13% to 19% higher risk of strokes.2 Thus, sex differences in arterial stiffness, and thence stiffness-related cardiovascular disease3–6 may explain the observation in the US and British nationallevel cohort analyses that age-related increase in heart disease mortality rates is blunted in men after 45 years of age but this is not seen in women.7 The basis of sex differences in carotid artery distensibility in middle aged and older adults are not well understood. Few published reports explore the association of sex hormones with arterial stiffness and distensibility, with inconsistent results in sex-specific studies and special populations for testosterone (T), estrogen and dehydroepiandrosterone (DHEA), as reviewed by Rossi et al.8 We aim to find the association of carotid artery distensibility with circulating levels of the sex hormones T, estradiol
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ultrasonography (E2), DHEA, and sex hormone–binding globulin (SHBG) in a large population-based US sample of middle aged and older men and postmenopausal women.
Methods Study Sample We analyzed data from the baseline examination of the Multi-Ethnic Study of Atherosclerosis (MESA, 2000–2002), including 5761 adult men and women for this analyses (enrollment strategy in Figure S1 in the online-only Data Supplement). The study was approved by the Institutional Review Boards of all participating institutions. Participants gave written informed consent. All procedures complied with international, federal, and institutional guidelines.
Clinical Examination and Risk Factor Covariates Participants self-reported their age and race/ethnicity, education, use of medications, smoking, physical activity, and menopause and the use of current hormone therapy in women. Seated blood pressure was measured as the average of the second and third readings taken using an automated oscillometric device. Total cholesterol categories (