Subclinical Differences in Myocardial Stiffness and Afterload Between Women and Men

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure and disproportionately affects women. Exercise intolerance is a common symptom and arises from impairments in exercise stroke volume reserve, increased afterload, and arterial and left ventricular stiffness. Whether women of all ages are more likely to experience similar impairments in exercise hemodynamics that are present in patients with HFpEF is unknown. The goal of our study was to determine whether subclinical changes in these measures during sedentary aging differed between sexes, potentially explaining the predisposition for HFpEF in women.

At #AHA23, we presented data from 194 healthy, sedentary, non-obese adults between the ages of 20 and 80 (mean age 57) who underwent a comprehensive high-resolution physiological assessment. Assessments included the use of cardiovascular magnetic resonance, carotid-femoral pulse wave velocity, right heart catheterization, and cardiopulmonary exercise testing. Men and women were compared on a per-decade basis.

Across participants’ ages, there were no differences in pulmonary capillary wedge pressure between women and men. While women had lower stroke volumes than men, stroke volume reserve, which is calculated as the percent increase in stroke volume from rest to exercise, was similar between men and women. Women demonstrated higher myocardial stiffness at each decade interval than their male counterparts, resulting in a lower left ventricular volume for any given pressure.

Central arterial stiffness was higher with each decade of life and was similar between women and men. Women had higher arterial elastance during exercise, a measure of afterload, at all ages compared to men. The higher arterial elastance observed in women was driven by smaller stroke volumes.

Despite low physical activity levels, both sexes at all ages could appropriately augment their stroke volume and had similar central arterial stiffness. In contrast, women had higher myocardial stiffness and arterial elastance compared to men. Whether the latter predisposes sedentary women to increased myocardial stiffness and left ventricular hypertrophy is currently unknown.

Hormonal factors, which change with aging, have been proposed as important contributors to sex-specific HFpEF risk. In future studies, we will explore the relationship between sex hormones and changes in cardiac and vascular function across age to understand how these may impact the differential risk of HFpEF between women and men.

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