CHANGES IN CARDIAC AND VASCULAR STRUCTURE AND FUNCTION WITH AGING IN HEALTHY SEDENTARY WOMEN

Abstract

Therapeutic Area: ASCVD/CVD in Women Background: As women age, structural and functional changes occur in the cardiovascular system that may predispose them to specific cardiovascular diseases. Heart failure with preserved ejection fraction (HFpEF) affects more women than men for reasons that are incompletely understood. A leading hypothesis suggests that increased vascular stiffness, left ventricular (LV) concentric hypertrophy, and decreased LV compliance after menopause contribute to the development of HFpEF. This study aimed to assess whether vascular stiffness, myocardial stiffness, and diastolic function differ between healthy premenopausal and postmenopausal women. Methods: Sixty-nine healthy, sedentary women (44% premenopausal, patient reported) underwent upright cardiopulmonary testing on a cycle ergometer and supine resting right heart catheterization (RHC). During exercise, we measured cardiac output (Q̇c; acetylene rebreathing) and oxygen uptake (V̇O2; Douglas bags); stroke volume (SV) was calculated from Q̇c and heart rate. At rest, we measured right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and transmural pressure (TMP = PCWP – RAP) from RHC. Furthermore, we assessed body composition (hydrodensitometry), aortic stiffness (carotid-femoral pulse wave velocity [aPWV]), and cardiac structure/function (echocardiography). Myocardial stiffness was assessed during LV loading and unloading to construct individual pressure-volume curves using the equation TMP=P∞(expa(v-v0)-1). Groups were compared using an independent-samples (Welch's) t-tests. Data are reported as mean ± standard deviation. Results: There were no statistically significant differences in V̇O2, Q̇c, or a-vO2 difference at rest or with exercise between the groups (Table 1). Postmenopausal women exhibited lower mitral annular systolic and diastolic excursion velocities and decreased systolic-diastolic coupling (e'VTI/s'VTI; Table 1). There were no statistically significant differences in PCWP, TMP, LVEDV, LV mass (Figure 1A & 1B) and resting and maximal exercise SV (Table 1) between groups. aPWV and SBP with maximal exercise was higher in postmenopausal women (Figure 1C), whereas myocardial stiffness did not differ between the groups (Figure 1D & 1E). Conclusions: Healthy, sedentary postmenopausal women demonstrate higher aortic stiffness, SBP response to exercise, and decreased systolic-diastolic coupling compared to premenopausal women. However, there were no significant differences in LV structure. Further studies are needed to understand the independent effects of aging and hormonal changes on vascular stiffening, diastolic function, and HFpEF risk in postmenopausal women.