Sex-specific lifetime risks of HFpEF and HFrEF in Europe

In a European population-based cohort study, the lifetime risk of incident HFrEF was higher in men, while women were at greater risk of developing HFpEF. Moreover, 8 modifiable risk factors substantially contributed to these risks, particularly in women.

This summary is based on the publication of Van Essen BJ, Emmens JE, Tromp J, et al. - Sex-specific risk factors for new-onset heart failure: the PREVEND study at 25 years. Eur Heart J. 2024 Dec 30:ehae868 [Online ahead of print]. doi: 10.1093/eurheartj/ehae868

Introduction and methods

Background

The incidence of HFrEF is higher in men than women, but it is unclear whether there is also a sex difference in the incidence of HFpEF. Of note, these results are based on only 2 cohort studies from the USA [1,2], and there are no European data available on the lifetime risk estimates to develop these HF types.

Aim of the study

The authors investigated the sex-specific lifetime risks of incident HFpEF and HFrEF and the impact of potentially modifiable risk factors in a large European cohort with a follow-up duration of 25 years.

Methods

In the current analysis, data were collected of 8558 participants (4268 men and 4290 women) from the extended follow-up phase of the observational PREVEND (Prevention of REnal and Vascular ENd-stage Disease) cohort, which ran from 1997 until January 1, 2022. The community-based PREVEND study was designed to investigate the association between microalbuminuria and incident cardiorenal disease in the general population (n=8592) [3]. The extended follow-up allowed for a more reliable estimation of the lifetime risk and increased the statistical power for assessment of the association between risk factors and the development of HF. Median follow-up duration of the current analysis was 23.4 years (i.e., 159,530 person-years).

Outcomes

The primary endpoints of the current study were: (1) lifetime risk of HF, HFpEF (LVEF ≥50%), and HFrEF (LVEF <50%), stratified by sex; and (2) population attributable fractions of 8 risk factors at baseline (hypertension, hypercholesterolemia, obesity, smoking, AF, CKD, MI, and diabetes mellitus) on the development of HF, HFpEF, and HFrEF, stratified by sex.

Main results

Lifetime risk of incident HF

• The overall lifetime risk of developing HF was 24.5% (95%CI: 22.4%–26.6%) in men and 23.3% (95%CI: 20.8%–25.8%) in women.

• For HFrEF, the lifetime risk was 18.1% (95%CI: 16.2%–20.0%) in men and 11.9% (95%CI: 10.0%–13.7%) in women, whereas the lifetime risk of HFpEF was 6.4% (95%CI: 5.2%–7.6%) in men compared with 11.5% (95%CI: 9.6%–13.4%) in women.

Population attributable fractions of HF risk factors

• For HFrEF, the cumulative population attributable fraction of all 8 potentially modifiable risk factors was 60% in men. The highest proportion was attributable to hypertension (23%), followed by hypercholesterolemia (20%), MI (18%), smoking (16%), and obesity (10%).

• In women, the cumulative population attributable risk for HFrEF was 71%. This cumulative risk was largely attributable to hypertension (39%), hypercholesterolemia (28%), and smoking (19%).

• The absolute difference in the cumulative population attributable fraction for HFrEF between men and women was 11% (95%CI: −2% to 23%; P=0.062).

• For HFpEF, the cumulative population attributable fraction of all potentially modifiable risk factors was 46% in men. The strongest risk factor was hypertension (30%), followed by obesity (16%) and diabetes (10%).

• In women, the cumulative population attributable fraction for HFpEF was 64%, which was largely driven by hypertension (46%), obesity (20%), and smoking (12%).

• The absolute difference in the cumulative population attributable fraction for HFpEF between men and women was 19% (95%CI: 6%–31%; P=0.049).

Conclusion

This European population-based cohort study with a 25-year follow-up showed that approximately 1 out of 4 individuals developed HF, with a similar incidence in men and women. However, the lifetime risk of incident HFrEF was higher in men than women (18% vs. 12%), whereas women were at greater risk of developing HFpEF than men (12% vs. 6%). Eight directly and indirectly modifiable risk factors were associated with most of the risk of developing HFrEF and HFpEF, particularly in women. In both men and women, hypertension and hypercholesterolemia were the strongest risk factors for HFrEF, whereas hypertension and obesity were the strongest risk factors for HFpEF. The authors conclude that “these findings support the notion that proactive screening of modifiable risk factors may have the potential to substantially reduce the incidence of HF, in particular in women.”

Find this article online at Eur Heart J.

References

1. Vasan RS, Enserro DM, Beiser AS, Xanthakis V. Lifetime risk of heart failure among participants in the Framingham study. J Am Coll Cardiol 2022;79:250–63. https://doi.org/10.1016/j.jacc.2021.10.043
2. Pandey A, Omar W, Ayers C, LaMonte M, Klein L, Allen NB, et al. Sex and race differences in lifetime risk of heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Circulation 2018;137:1814–23. https://doi.org/10.1161/CIRCULATIONAHA.117.031622
3. Hillege HL, Fidler V, Diercks GFH, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002;106:1777–82. https://doi.org/10.1161/01.CIR.0000031732.78052.81