Why are women more likely than men to develop heart failure with preserved ejection fraction?

Women are approximately two times more likely than men to develop heart failure in the setting of preserved left ventricular ejection fraction [i.e. heart failure with preserved left ventricular ejection fraction (HFpEF)], but the reasons for this disparity are unknown.

HFpEF is caused by changes in ventricular-vascular properties that are associated with aging and hypertensive cardiac remodeling. These changes lead to diastolic and systolic dysfunction and impaired reserve capacity. Many of the cardiovascular alterations seen in HFpEF are also noted to greater extent in women compared with men. Women demonstrate more concentric left ventricular remodeling and less ventricular dilatation in response to arterial hypertension. Ventricular and arterial stiffness increases with age in both sexes, but the increase is more dramatic in women. Recently, age-sex interactions have also been observed in the manner in which left ventricular function changes across the lifespan, wherein systolic and diastolic function and functional reserve become more compromised in women as compared with men in the postmenopausal years, despite similar or enhanced function in women during youth.

The prevalence of HFpEF is increasing and women outnumber men by a 2 : 1 ratio. Recent data have identified striking parallels between structure-function alterations observed in HFpEF and sex differences in cardiovascular function across the adult lifespan. These data suggest that sex-specific maladaptations to hypertensive aging in women may underlie greater risk of HFpEF.