Sex Differences in HFpEF

Abstract

Heart failure with preserved ejection fraction (HFpEF) disproportionately affects women. Though no unifying theory exists to explain this phenomenon, the purpose of this review is to explore the many factors that likely contribute to this female predominance. Inflammation and microvascular ischemia are increasingly thought to play a role in promoting HFpEF, as is the presence of cardiometabolic traits including hypertension, diabetes, and obesity. All of these factors are more common in women. Female-specific risk factors, including a history of hypertensive disorders of pregnancy and sequelae of breast cancer therapy, can further contribute to a woman’s risk. No targeted therapies exist for the management of HFpEF, but some therapies, including sacubitril/valsartan, have shown differential benefit in women. Though women with HFpEF have better outcomes than men, they have worse self-reported quality of life. More work is required to address these and other sex disparities. This review summarizes what is known about the pathophysiology of HFpEF, leading theories to explain this female predominance, sex-specific differences in the objective findings of HFpEF, outcomes, and response to therapies, and what work remains to be done.