Date Published: April 4, 2019
Publisher: Public Library of Science
Author(s): Hidemi Sorimachi, Koji Kurosawa, Kuniko Yoshida, Masaru Obokata, Takashi Noguchi, Minoru Naka, Shoichi Tange, Masahiko Kurabayashi, Kazuaki Negishi, Tatsuo Shimosawa.
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.
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. Women had worse LV relaxation than men did against the same degree of afterload, before and even after adjusting for the aortic sizes.
Heart failure (HF) is a major clinical and public health problem owing to its high prevalence, mortality, hospitalization, and healthcare expenditures. Relative prevalence of HF with preserved ejection fraction (HFPEF) to HF with reduced EF (HFREF) is rising over time; yet the survival in HFPEF has remained dismal due to the lack of proven therapies. Several large clinical trials for HFPEF have demonstrated neutral results.[2–4] Further elucidation of the mechanisms underlying HFPEF may aid in identifying a novel therapeutic target.
This is the first study which assessed whether the aortic size alters the magnitude of sex difference between LV diastolic function and afterload. Through a comprehensive hemodynamic evaluation of elderly patients with preserved EF, we found 1) that only weak associations were found between BSA and the aortic sizes (length and volume) measured with CT; 2) that we confirmed statistically significant sex differences in the relationships between LV diastolic function and afterload in our population; 3) that adjusting for the aortic sizes had minimal effects on the sex dimorphism; 4) that sex differences were independent from the aortic sizes, more accurate anatomical parameters of the vascular sizes; and 5) that among the afterload parameters, aggressive BP lowering would be more beneficial in women than in men because sex difference was more prominent between diastolic function and BPs.
Significant sex differences in the relationships between LV diastolic functions and afterload were confirmed in elderly patients with preserved ejection fraction. Women had worse LV relaxation compared to those in men with the same degree of afterload, before and after adjusting for the aortic sizes.