Sex-specific Limitation of Cardiac Capacity during the Adult Lifespan: Return to Fundamental Structure and Function

Abstract

Abstract Physiology underlying reduced cardiac pumping capacity in women compared with men and its interaction with aging remains unresolved. Herein, the pressure gradient (PG) driving venous return was manipulated to evidence whether cardiac structure and/or function explain sex differences in cardiac capacity. Healthy women/men matched by age and physical activity were included within young (n=40, age=25±4 yr) and older (n=55, age=60±8 yr) groups. Cardiac volumes/output (Q) were assessed up-to-peak exercise under two hemodynamic conditions (‘low’/‘high’ PG between lower/upper body). Main outcomes included sex differences in delta (‘high’­‘low’ PG) left ventricular (LV) end-diastolic volume (∆LVEDV), stroke volume (∆SV) and Q (∆Q). In young individuals, ‘high’-PG increased exercise LVEDV and SV in men (P≤0.002), but not in women (P≥0.562), relative to ‘low’-PG (control condition). Accordingly, peak ∆LVEDV, ∆SV and ∆Q were enhanced in young men versus young women (P≤0.019). Notwithstanding, right/left atrial volumes during exercise were similarly increased by ‘high’-PG in both young sexes (P≤0.007). ‘High’-PG exclusively prolonged moderate exercise LV filling time in young men (P≤ 0.036). In older individuals, ‘high’-PG did not modify exercise cardiac volumes and reduced LV diastolic function (P≤0.049). In conclusion, the female young heart is unrestrained by venous return or structural factors external to the myocardium. As determined during moderate exercise, impaired LV filling time lengthening limits female-specific cardiac capacity. With older age, cardiac chambers are not distended and LV relaxation is impaired with increased PG in both sexes. During early but not late adulthood, a functional LV limitation may explain sex differences in cardiac capacity.