What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with preserved ejection fraction (HFpEF) (n=1727). Intervention: Biological age acceleration (KDMAge) vs. Lower biological age acceleration. Primary outcome: All-cause mortality (HR 1.55, 95% CI 1.40-1.72, p=<0.001).

December 17, 2025npj Aging1 citationsOpen Access

Biological aging, left ventricular dysfunction and mortality in patients with heart failure with preserved ejection fraction

Q: What are the key findings of this study?

Per 1-SD increase in KDMAge biological age acceleration was associated with a significantly higher risk of all-cause mortality (HR 1.55) in patients with heart failure with preserved ejection fraction.

XXXinghao XuSun Yat-sen University ZHZihao HuangSun Yat-sen University XXXingfeng XuShanghai Polytechnic University

Key Result

Per 1-SD increase in KDMAge biological age acceleration was associated with a significantly higher risk of all-cause mortality (HR 1.55) in patients with heart failure with preserved ejection fraction.

Study Design

Type

Cohort (n=1,727)

Multicenter

Structured PICO

Does biological aging acceleration predict mortality and left ventricular dysfunction in patients with HFpEF?

Population

1,727 patients with heart failure with preserved ejection fraction (HFpEF) from the RED-CARPET Study

Intervention

Biological aging (BA) acceleration assessed using Klemera-Doubal and PhenoAge methods

Outcome

All-cause mortality and cardiovascular mortality at median 4.9-year follow-uphard clinical

Accelerated biological aging is significantly associated with increased all-cause and cardiovascular mortality, as well as left ventricular dysfunction, in patients with HFpEF.

Main Result

Effect estimate: HR 1.55 (95% CI 1.40-1.72)

p-value: p=<0.001

Limitations

Retrospective recruitment from a single tertiary hospital may introduce selection bias
Biomarkers were measured only at baseline, precluding assessment of longitudinal changes
High proportion of hypertensive HFpEF patients may restrict generalizability
KDMAge and PhenoAge algorithms were developed from a U.S. cohort and applied without recalibration
Observational design means reverse causation and residual confounding cannot be fully excluded

Abstract

Accelerated biological aging (BA) is linked to adverse cardiovascular events, but its role in heart failure with preserved ejection fraction (HFpEF) remains unclear. We analyzed 1,727 HFpEF patients from RED-CARPET Study (ChiCTR2000039901), assessing BA using Klemera-Doubal and PhenoAge methods. During a median 4.9-year follow-up, 321 all-cause and 180 cardiovascular deaths occurred. After full adjustment, per 1-SD increase in BA acceleration showed significantly higher risk of all-cause mortality (KDMAge HR 1.55, 95% CI 1.40-1.72; PhenoAge HR 1.24, 95% CI 1.11-1.40) and cardiovascular mortality (KDMAge HR 1.47, 95% CI 1.28-1.69; PhenoAge HR 1.21, 95% CI 1.04-1.41). BA acceleration was also significantly related to increased left ventricular mass index (LVMI), relative wall thickness, and E/e' ratio. Mediation analysis revealed that both LVMI and the E/e' ratio partially mediated the relationship between BA acceleration and mortality. These findings suggest BA acceleration may serve as a key prognostic marker in patients with HFpEF.

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