Use of FGF-23 and sαKlotho for Risk Stratification in Patients with Acute Heart Failure

J Clin Med. 2025 Jan 28;14(3):860. doi: 10.3390/jcm14030860.

Abstract

Background/Objectives: Soluble αKlotho (sαKlotho) and fibroblast growth factor 23 (FGF-23) are increased in acute heart failure (AHF). This study aimed to assess changes in serum sαKlotho and FGF-23 concentrations during an episode of AHF as well as the usefulness of both biomarkers for predicting long-term prognosis. Methods: The study included 104 consecutive patients hospitalized in t he intensive cardiac care unit due to AHF (mean age, 65.8 ± 14.6 years; mean ejection fraction, 31.4% ± 14). New-onset AHF was reported in 43.3% of the population. Blood samples were measured at entry and on discharge from hospital. The main clinical outcomes assessed in this study were all-cause mortality or rehospitalization due to HF during a 3-year follow-up. Results: At admission sαKlotho, FGF-23, and NT-pro BNP levels, compared with discharge, were significantly higher at p < 0.001, p < 0.001, and p < 0.001 respectively. The 3-year Kaplan-Meier analysis, based on tertiles, revealed, for sαKlotho levels from Tertile 1 on admission and at discharge, a 2-fold higher rate of all-cause mortality or rehospitalization for HF compared with Tertile 3 (p = 0.006 and p = 0.028, respectively). One-third of patients showed an increase in FGF-23 and sαKlotho levels during hospitalization. Patients with the highest percentage increase in the levels of both biomarkers had an elevated risk of all-cause morality or hospitalization for HF (hazard ratio, 2.75; confidence interval, 1.19-6.35; p = 0.02). Conclusions: sαKlotho and FGF-23 levels are elevated during an episode of AHF. Low sαKlotho levels are associated with an increased risk of all-cause mortality or rehospitalization for HF. Increases in sαKlotho and FGF-23 values during hospitalization identify patients with poor prognosis.

Keywords: acute heart failure; biomarker; fibroblast growth factor 23; prognostication; soluble αKlotho.