Abstract 4144437: Limited Effect of Circulating Sex Hormones on Cardiac and Vascular Physiology with Healthy Aging

Background: Sex differences in cardiac and vascular aging, including the disparate risk for heart failure with preserved ejection fraction (HFpEF) in women may be mediated by declines in sex hormones. It is unknown if hormone levels affect subclinical cardiovascular changes with aging that predispose women to HFpEF; therefore, we compared hormone levels and afterload, arterial and left ventricular (LV) stiffness across age in healthy men and women. Methods: We studied 194 sedentary normotensive, non-obese adults (55% female; age: 21-88yrs) at rest and maximal exercise. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (PWV). Afterload was assessed at rest with aortic augmentation pressure (aAP), calculated from reconstructed ascending aortic blood pressure (BP) waveforms (SphygmoCor), and at maximal exercise as effective arterial elastance (Ea; systolic BP/stroke volume [derived from C 2 H 2 rebreathe]). Myocardial stiffness was assessed as the slope of individual pressure-volume (right heart catheterization-echocardiography) curves generated by graded LV loading and unloading. Serum Testosterone (T), estradiol, and follicle stimulating hormone (FSH) were measured (TOSOH Bioanalyzer). The effect of age, sex, and hormones were assessed via multivariate linear regression. Results: FSH increased exponentially with age with higher levels in women (Figure A, p<0.001). FSH was associated with Ea (p=0.048, β=0.003) with a small effect size, but not aAP (p=0.078, β=0.017). The effect for FSH was eliminated when adding a sex*hormone level term (Figure B). T declined at >3-fold the rate with age in men (Figure A, p<0.001) and was associated with Ea, also with a small effect size (p=0.041, β=0.001, Figure B). There was no association between FSH or T with arterial or myocardial stiffness (all, p>0.565, β<0.002). Conclusion: Higher exercise afterload with increasing age in women was associated with progressively higher levels of FSH and lower levels of T. In healthy adults, the effects of circulating sex hormones were small relative to the effects of age and sex, and therefore likely do not explain the elevated HFpEF risk in women.