Fibroblast Growth Factor 21 Predicts Short-Term Prognosis in Patients With Acute Heart Failure: A Prospective Cohort Study

Abstract

Background: Recent studies of fibroblast growth factor 21 (FGF21), first recognized as a regulator of glucose and lipid metabolism, have found that the level of in serum FGF21 is associated with the prognosis of many cardiovascular diseases, but its relationship to acute heart failure (AHF) patients remains unknown. Our study aimed to investigate whether circulating FGF21 could predict the short-term prognosis of AHF patients.

Methods: Four hundred and two AHF patients and 19 healthy controls were recruited into the prospective cohort study, and blood samples of participants were collected, in tubes without anticoagulant, within the first 24 h after hospital admission. Serum FGF21 levels were detected by enzyme-linked immunosorbent assay (ELISA). All patients were followed-up at least 6 months after discharge. The primary endpoint was all-cause death, and secondary endpoint was a composite endpoint of death and heart failure readmission. Mortality and composite end point events were analyzed using Kaplan-Meier curves. ROC curves compared the difference between the FGF21 and NT-proBNP in predicting 3- and 6-months mortality. Time-to-event data were evaluated using Kaplan-Meier estimation and Cox proportional hazards models.

Results: In the present study, the serum FGF21 concentrations were significantly higher in the 402 AHF patients enrolled, compared with the 19 healthy controls (p < 0.001). The average age was 70 (±12) years, and 58% were males. Participants were divided into two groups according to the median FGF21 level (262 pg/ml): a high FGF21 group (n = 201, FGF21 ≥ 262 pg/ml) and low FGF21 group (n = 201, FGF21 <262 pg/ml). FGF21 was positively correlated with NT-proBNP, BUN, AST, creatinine and cholesterol, and negatively correlated with ALB and HDL. After a median follow-up of 193 days, the high FGF21 group had higher mortality and composite endpoint events compared with the low FGF21 group (HR: 3.91, 95% CI 2.21-6.92, p <0.001), even after adjusting for NT-proBNP (HR: 3.17, 95% CI 1.72-5.81, p < 0.001). ROC analysis shows that FGF21 was better than NT-proBNP in predicting death at both 3 (AUC, 0.77 vs. 0.63, p < 0.001) and 6 months (AUC, 0.78 vs. 0.66).

Conclusion: High baseline FGF21 levels are associated with adverse clinical outcomes in AHF patients. Serum FGF21 might be a potential predictive biomarker of AHF patients.

Keywords: FGF21; acute heart failure; biomarker; death; prognosis.

Figure 1

Flow chart of the study and outcome for the AHF cohort. AHF, acute heart failure.

Figure 2

Serum FGF21 is higher in AHF patients (n = 402) compared to the healthy controls (n = 19) (p < 0.001) (A). Concentration of FGF21 (B) and NT-proBNP (C) were increased with the increase in New York Heart Association (NYHA) functional class (p < 0.001 for trend). NT-proBNP gradually decreased from HFrEF, HFmrEF to HFpEF patients (p = 0.002 for trend) (E), but not FGF21 (p = 0.843 for trend) (D).

Figure 3

Correlation heat map shows the correlation between serum FGF21 and biochemical parameters, BNP, and EF values in AHF patients. Those with statistical significance (p < 0.05) are presented as dot plots. ALB, albumin; A/G, albumin/globulin; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Cr, creatinine; Chol, cholesterol; GLB, globulin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NT-proBNP, N-terminal brain natriuretic peptide; TG, triglyceride; TP, total protein.

Figure 4

Kaplan-Meier curves for all-cause death (A) and composite endpoints (B) stratified by FGF21 median in AHF patients. Mortality (A) and composite endpoints (B) were significantly higher in the high FGF21 group than the low FGF21 group (p < 0.001).

Figure 5

Subgroup analyses of all-cause death vs. the low FGF21 group. CAD, coronary artery disease; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.