Abstract

Introduction: Mechanisms mediating the disproportionate risk for heart failure with preserved ejection fraction (HFpEF) in women are poorly understood. Impaired stroke volume (SV) reserve, increased afterload, arterial and left ventricular (LV) stiffness contribute to exercise intolerance in HFpEF. It is unknown whether subclinical changes in these measures predispose women to HFpEF; therefore, we compared resting and exercise cardiovascular structure and function across age in healthy men and women. Methods: We studied 192 sedentary normotensive, non-obese adults (53% female; age: 58 ± 13 [20-90] years) at rest, during sub- and maximal exercise. We measured systolic blood pressure (SBP; electrosphygmomanometry) and aortic stiffness (carotid-femoral pulse wave velocity; aPWV). Myocardial stiffness was assessed as the slope of individual pressure-volume (right heart catheterization-echocardiography) curves generated by graded LV loading and unloading. SV was calculated from cardiac output (Q˙c; C 2 H 2 rebreathe)/heart rate to assess afterload (Ea; SBP/SV) and SV reserve (% change from rest) during exercise. Data were compared via two-way ANOVA (age*sex). Results: There was no significant age*sex interaction for aPWV, SV reserve, resting or maximal SBP, or myocardial stiffness; however, there was a main effect for sex with higher myocardial stiffness in women (Figure). aPWV and SV reserve were not different between sexes (p=0.349, p=0.940). Maximal exercise SBP was lower in women, but a similar proportion of each sex had an exaggerated maximal exercise SBP (Men: >210; Women: >190 mmHg; 28% vs 35%, χ 2 =0.290). Peak exercise afterload was higher in women (Figure) due to lower SV. Conclusions: Increased risk for HFpEF in women may be driven in part by greater myocardial stiffness throughout the aging process. Sex related abnormalities in afterload were most prominent with exercise in women, which may predispose to LV hypertrophy and increased stiffness.

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