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

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.