Sex Differences in Characteristics and Outcomes in Elderly Heart Failure Patients With Preserved Ejection Fraction: A Post-hoc Analysis From TOPCAT

Abstract

Introduction: Although the impact of sex on patient outcomes for heart failure (HF) with preserved ejection fraction (HFpEF) has been reported, it is still unclear whether this impact is applicable for elderly patients with HFpEF. This study was conducted as a secondary analysis from a large randomized controlled trial—The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT)—to evaluate the impact of sex differences on the baseline characteristics and outcomes of HFpEF patients who were older than 70 years.Methods: Baseline characteristic of elderly patients were compared between men and women. Primary outcomes were cardiovascular (CV) mortality and HF-related hospitalization, whereas secondary outcomes were all-cause mortality and all-cause hospitalization. Cox regression models were used to determine the effect of sex differences on patient outcomes.Results: A total of 1,619 patients were included in the study: 898 (55.5%) women and 721 (44.5%) men. Age was similar between women and men. Women had fewer comorbidities but worse cardiac function than men. The rate of primary outcomes was lower in women than in men (18.4 vs. 27.5%; p < 0.001), including rate of CV mortality (8.9 vs. 14.8%; p < 0.001) and HF-related hospitalization (13.4 vs. 18.2%; p = 0.008). All-cause mortality was also lower in women than in men (15.6 vs. 25.4%; p < 0.001). After adjustment for baseline characteristics, Cox regression analysis showed that female sex was a protective factor for CV mortality [hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.40–0.73], HF-related hospitalization (HR: 0.71; 95% CI: 0.55–0.93), and all-cause mortality (HR: 0.59; 95% CI: 0.47–0.75). Although spironolactone significantly reduced the rate of all-cause mortality in women even after adjusting for baseline characteristics (HR: 0.68; 95% CI: 0.48–0.96; p = 0.028), no significant multivariate association was noted between sex and treatment effects (p = 0.190).Conclusion: Among elderly patients with HFpEF, women had worse cardiac function but better survival and lower HF-related hospitalization rate than men.Clinical Trial Registration: NCT00094302 (TOPCAT). Registered October 15, 2004, https://www.clinicaltrials.gov/ct2/show/NCT00094302.

Imaging of heart disease in women: review and case presentation

“…HFpEF can also be the manifestation of specific cardiomyopathies, such as inherited or acquired infiltrative cardiomyopathies (including cardiac amyloidosis), restrictive cardiomyopathies, myocarditis, or genetic cardiomyopathies [ 120 ]. Notably, women with HFpEF have a better prognosis than men with HFpEF, with less mortality despite a higher re-hospitalization rate, which could possibly reflect a sex difference in spironolactone treatment impact on all-cause mortality [ 122 ].…”

Diastolic dysfunction and sex-specific progression to HFpEF: current gaps in knowledge and future directions

“…Data on mortality and hospitalization, however, are not consistent. Three studies reported significantly better outcomes in women with HFpEF compared to men with HFpEF [ 55 , 131 , 132 ]. Also, women with HF were more frequently admitted for non-cardiovascular causes [ 130 ], and women hospitalized with HFpEF were at higher risk of poor post-discharge outcomes (adjusted HR = 1.54 (95% CI: 1.14, 2.07) than men [ 133 ], which may be due to high comorbidity burden in women.…”

“…Also, women with HF were more frequently admitted for non-cardiovascular causes [ 130 ], and women hospitalized with HFpEF were at higher risk of poor post-discharge outcomes (adjusted HR = 1.54 (95% CI: 1.14, 2.07) than men [ 133 ], which may be due to high comorbidity burden in women. This high comorbidity burden together with a higher prevalence of obesity and worse diastolic and vascular function and greater exercise limitations might reflect different HFpEF etiologies and can partly explain the inconsistencies in prognostic studies [ 39 , 131 , 134 , 135 ]. Additionally, women with HFpEF have a worse quality of life compared to men with HFpEF, and this is also consistently observed in the general community [ 134 ].…”

Sex-Specific Impairment of Cardiac Functional Reserve in HFpEF

“… 9 Although women and men share the same risk for adverse outcomes in heart failure with reduced ejection fraction, inconsistent evidence exists on differing mortality rates in between both sexes in HFpEF. 10 , 11 , 12 Varying onset of symptomatic burden initiating clinical consultation and differences in disease progression within both sexes could be a reason to heterogeneous mortality rates. 13 Female patients tend to be more prone to metabolic stress than men 14 and have an increased risk of congestive heart failure as a response to hypertension.…”