Sex differences in left ventricular afterload and diastolic function are independent from the aortic size

BACKGROUND: Women have a greater risk of heart failure with preserved ejection fraction (HFPEF) than men do, yet the basis for this disparity remains unclear. Greater arterial stiffness and afterload causes left ventricular (LV) diastolic dysfunction, a central mechanism of HFPEF. Because of smaller body habitus, previous reports have used body surface area as a surrogate of the size of the aorta. We performed a comprehensive hemodynamic evaluation of elderly patients with preserved EF and evaluated sex differences in the associations between LV function and afterload, before and after adjusting for the aortic sizes. METHODS AND RESULTS: Four hundred and forty-three patients (mean age: 73 years, 169 women) who underwent clinically indicated echocardiography and computed tomography (CT) were identified. Linear regression analyses were performed to assess the independent contributions of sex to and its interaction with LV function before and after adjusting for CT-derived aortic length and volume. Although blood pressures were similar between the sexes, women had greater arterial elastance, lower arterial compliance, and greater LV ejection fraction (all p<0.001). Sex differences were detected in the associations between LV afterload and relaxation (mitral e′) as well as in the left atrial (LA) emptying fraction, but not in LA size. These differences remained significant after adjusting for the aortic length and volume. Sensitivity analyses in an age-matched subgroup (n = 324; 162 of each sex) confirmed the robustness of these sex disparities in LV diastolic function and afterload. CONCLUSION: Women had worse LV relaxation than men did against the same degree of afterload, before and even after adjusting for the aortic sizes.