Circulating fibroblast growth factor 21 predicts adverse outcomes in patients with pre-heart failure and HFpEF

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of patients with heart failure. Given its complex pathogenesis, non-invasive biomarkers are urgently needed. Fibroblast growth factor 21 (FGF21) modulates metabolism and inflammation, yet its prognostic role in the development and progression of HFpEF remains unclear. This observational study enrolled 609 patients with pre-heart failure, characterized predominantly by diastolic dysfunction, and 297 patients with HFpEF. Baseline FGF21 concentrations were measured. All enrolled patients underwent a median follow‑up of 3.5 years. Cox regression analyses demonstrated that FGF21 had limited predictive value for progression to HFpEF in patients with pre-heart failure. However, FGF21 independently predicted the composite endpoint of recurrent heart failure hospitalization and all-cause mortality among patients with HFpEF. The hazard ratios remained relatively stable across HFpEF patient subgroups stratified by age, BMI, hypertension, diabetes, NYHA class, and eGFR. In conclusion, our study demonstrates that circulating FGF21 acts as an independent predictor of recurrent heart failure and all-cause death in patients with HFpEF, and may serve as a promising auxiliary biomarker for risk stratification of patients with HFpEF in clinical practice.