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.