Obesity and Heart Failure With Preserved Ejection Fraction in Women: The Interplay of Sex-Specific Pathophysiology and Clinical Implications

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and disproportionately affects women, particularly in the context of obesity.Understanding the sex-specific pathophysiology underlying HFpEF is critical for developing targeted management strategies.This review synthesizes evidence from epidemiological cohorts, mechanistic studies, and clinical trials to explore the interplay between obesity and female sex in the development and manifestation of HFpEF.Emphasis is placed on hormonal influences, inflammatory pathways, microvascular dysfunction, and metabolic alterations, with obesity highlighted as a central modifiable risk factor.HFpEF in women-especially when associated with obesity-represents a distinct clinical and pathophysiological entity.Recognizing sex-specific mechanisms is essential for advancing personalized diagnostic and therapeutic approaches.Multidisciplinary care and focused research into female-specific HFpEF pathways are urgently needed to address this emerging public health challenge.