Background:
The number of the patients with heart failure with preserved ejection fraction (HFpEF) has been rapidly increasing worldwide. However, sex differences in patients with HFpEF remain to be elucidated.
Methods and Results:
We examined sex differences in 3,124 consecutive patients with HFpEF (EF≥50%, mean 69.4years, 34.7% female) registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). Female patients, as compared with male patients, were characterized by higher age (72 vs. 68 years, P<0.01), higher LVEF (67 vs. 64%, P<0.01), higher heart rate (74 vs. 70bpm, PNYHA class III (14.1 vs. 7.0%, P<0.01), higher BNP levels (106 vs. 73pg/mL, P<0.01), lower prevalence of coronary artery disease (30 vs. 53%, P<0.01) and lower prescription rates of renin angiotensin system inhibitors (64.7 vs. 71.8%, P<0.01) and beta-blockers (37.8 vs. 43.9%, P<0.01). During the median 3.2-year follow-up, 147 female patients and 245 males died. Although there was no sex difference in all-cause mortality (13.6 vs. 12.0%, P=0.11), female patients more frequently died due to cardiovascular causes (53.7 vs. 39.2%, hazard ratio (HR): 1.62, 95% CI 1.20-2.18, P<0.01), and experienced more HF admissions (12.6 vs. 9.8%, HR: 1.35, 95% CI 1.08-1.68, P<0.01). Use of beta-blockers or renin-angiotensin system inhibitors was not associated with decreased incidence of death or HF admission in both sexes. In contrast, use of statins was associated with reduced incidence of all-cause death in both sexes (males and females; adjusted HR, 0.59 and 0.57; 95% CI 0.46-0.77 and 0.47-0.70, respectively, both P<0.01) and was also associated with reduced incidence of HF admission in males (adjusted HR: 0.67, 95%CI 0.53-0.85, P<0.01) but not in females (adjusted HR: 0.83, 95% CI 0.63-1.10, P=0.19).
Conclusions:
As compared with males, female patients with HFpEF were characterized by severer condition of HF and increased risk of cardiovascular death and HF admission. Although statin use was equally associated with improved mortality in both sexes, female patients with HFpEF may benefit from statins less than males in terms of reduction of HF admission.
Sex differences in the metabolic effects of the renin-angiotensin system
