Abstract P065: Cross-Sectional and Prospective Associations of the Cortisol/testosterone and Cortisol/ Sex Hormone Binding Globulin Ratios With Atherosclerosis in Women

Abstract

Introduction: The ability to study chronic stress in humans is complicated due to measurement error of questionnaires and the inability of short-term measures of stress hormones to reflect the chronic state. Therefore considerable controversy remains about whether chronic stress influences atherosclerosis or not. The cortisol/testosterone (C/T) ratio was suggested to be a better predictor of heart disease in men than cortisol alone, as gonadotropin and cortisol are derived from the same biochemical precursor. This ratio has never been studied in a U.S. epidemiologic study, especially in women. Study question: Are C/T and C/sex hormone binding globulin (SHBG) ratio associated with subclinical atherosclerosis in women? Methods: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 367 women (age range 32 to 51, mean age 40 years old) who had both cortisol from year (Y) 15 and sex hormones from serum specimen Y16 measured are included. Intima-media thickness (IMT) from Y20 was assessed cross-sectionally. Coronary artery calcium (CAC) incidence from Y15-25 was assessed prospectively where available (n=299). Due to the instability and diurnal characteristics of cortisol, area under the curve (AUC) of six samples and slope of 1st (or 3rd) and 6th (or 5th when 6th is not available) sample of salivary cortisol collected over one day were calculated. Ratios of AUC and of slope of cortisol to total testosterone (TT), free testosterone (FT), and sex hormone binding globulin (SHBG) were computed: AUC/TT, AUC/FT, AUC/SHBG, Slope/TT, Slope/FT, and Slope/SHBG. The associations of these variables categorized into tertiles with CAC and IMT were assessed by logistic regression analysis (CAC) and multiple linear regression (IMT). Model I controlled for age and race. Model II controlled for model I variables plus BMI, systolic BP, menopause, oral contraceptive usage, diabetes mellitus, alcohol consumption, and cigarette smoking. Results: The highest tertile of AUC/FT ratio was associated with Y20 carotid bulb IMT max in model I (β=0.07, p=0.031) and model II (β=0.09, p=0.006). This ratio also had moderate OR with incident CAC from Y15 to Y25 in model I (OR 2.22, 95% CI 0.89-5.51) and had significant association in model II (OR 3.45, 95% CI 1.18-10.06). Conclusions: Findings suggest that AUC/FT ratio is cross-sectionally and prospectively associated with subclinical atherosclerosis in women.