Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is more common in older women than men. Differences in sex hormone (SH) levels may contribute to sex differences in HFpEF risk. Left ventricular (LV) hypertrophy and concentric remodeling [increased Mass (M): Volume (V) ratio] are risk markers of HFpEF. In a multi-ethnic cohort of men and women with preserved EF, we examined whether SH levels were associated with LV structure. We hypothesized that a more androgenic pattern would predict adverse concentric remodeling in women but not men. Methods: We studied 4279 MESA participants (49% women) aged 45-84 yrs with serum SH levels and cardiac MRI performed at baseline (2000-2002) and baseline EF ≥50%. Among these, 2957 participants underwentMRI at Exam 5 (2010-2012). Stratified by sex, we used linear regression for cross-sectional analyses and mixed model effect methods for longitudinal analyses to test the associations of SH and binding globulin (SHBG) levels [per 1 SD greater log(SH)] with baseline levels and changes in LV mass (LVM), end diastolic volume (LVEDV) and M:V ratio. Models were adjusted for age, ethnicity, center, height, weight, education, physical activity and smoking, and for hormone use and menopause in women. Results: The mean (SD) age was 64 (9) for women and 62 (10) yrs for men. Cross-sectionally, among women, higher Testosterone (T) and Dehydroepiandrosterone (DHEA) levels were associated with greater LVM ( Table ). Among both men and women, higher free T and lower SHBG were associated lower LVEDV and greater M:V ratio. In men, greater estradiol levels were associated with lower LVEDV and greater M:V ratio. After a mean followup of 10 yrs, higher free T and lower SHBG were associated with an increase in LVM in both sexes. Findings were generally consistent after adjustment for possible mediators of these associations such as blood pressure and other CV risk factors. Conclusion: A more androgenic profile of higher free T and lower SHBG is associated with greater increase in LVM over 10 yrs in both men and women.

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