Sex‐Specific Outcomes and Treatment Responses in Elderly Patients With Heart Failure With Preserved Ejection Fraction: A Comprehensive Single‐Center Retrospective Study

Background Heart failure with preserved ejection fraction (HFpEF) disproportionately affects elderly women, with potential contributions from sex‐specific hormonal and physiological factors. We aimed to evaluate sex‐specific prognostic differences, comorbidity impacts, and guideline‐directed medical therapy effects in elderly patients with HFpEF. Methods Retrospective analysis of 603 patients (age ≥60 years, male: 51.6%, mean age: 79.10±9.19 years) newly diagnosed with HFpEF at Huadong Hospital, Fudan University (from July 2019 to June 2024) with follow‐up through December 2024. The primary outcome was all‐cause mortality. Results The overall mortality rate was 14.2/100 person‐years (women: 15.4 versus men: 13.2). Based on the gender and etiology phenotype classification for HFpEF, patients with types I/IV HFpEF had better survival (10.0/12.4 per 100 person‐years) versus those with types II/III/V (17.1/22.9/24.2 per 100 person‐years). Sex‐specific mortality peaks differed, with men having type V in 30.3/100 person‐years and women having type III in 28.2/100 person‐years. In Cox regression analysis, after adjusting for age, sex, body mass index, and hypertension, type 2 diabetes and stages 4 or 5 chronic kidney disease predicted mortality in men only (chronic kidney disease 4 or 5: hazard ratio [HR], 3.24, type 2 diabetes: HR, 2.34; both adjusted P <0.05) but not in women (adjusted P >0.1). After adjusting for age, body mass index, hypertension, type 2 diabetes, and renal dysfunction, angiotensin receptor neprilysin inhibitors reduced mortality in women (HR, 0.57; adjusted P =0.027), while sodium‐glucose cotransporter‐2 inhibitors reduced mortality in men (HR, 0.25; adjusted P =0.021). Conclusions Mortality patterns, comorbidity impacts, and treatment responses in elderly patients with HFpEF exhibit significant sex disparities. This underscores the need for sex‐tailored management to optimize outcomes. These findings should be interpreted with caution given the retrospective design.