Prognostic Impact of Fibroblast Growth Factor 21 in Patients With Heart Failure

• Published in: Circulation Reports p. CR-25-0067
• Main Authors: Sunaga, Hiroaki, Yoshida, Kuniko, Kagami, Kazuki, Harada, Tomonari, Murakami, Tsukasa, Yuasa, Naoki, Matsui, Hiroki, Kawai-Kowase, Keiko, Iso, Tatsuya, Yokoyama, Tomoyuki, Kurabayashi, Masahiko, Ishii, Hideki, Obokata, Masaru
• Format: Journal Article
• Language: English
• Published: The Japanese Circulation Society 29.08.2025
• Subjects: Fibroblast growth factor; Heart failure; Prognosis
• ISSN: 2434-0790; 2434-0790
• DOI: 10.1253/circrep.CR-25-0067

Background: Systemic and cardiac metabolic disorders play a key role in patients with heart failure (HF). Fibroblast growth factor 21 (FGF21) is mainly secreted from the liver and has various effects on cardiomyocytes, including protection against oxidative stress, cardiac hypertrophy, and inflammation. However, the pathophysiologic and prognostic impact of FGF21 remains unknown.Methods and Results: Serum levels of FGF21 and echocardiography were performed in patients with compensated HF (n=162) and control patients without HF (n=20). Compared with the control patients, those with HF displayed higher FGF21 levels (100 [76–213] vs. 237 [135–575] pg/mL; P=0.0006). There were no or modest correlations of FGF21 levels with clinical variables and echocardiographic parameters. During a median follow up of 12.0 months, there were 56 primary composite endpoints of all-cause death or HF hospitalization in the HF cohort. The highest FGF21 tertile was associated with a 3-fold increased risk of the composite outcome compared with the lowest tertile. After adjusting for age, sex, and the presence of atrial fibrillation, serum FGF21 remained independently associated with the outcome. Adding FGF21 levels to the model based on N-terminal pro B-type natriuretic peptide levels significantly improved the prognostic value (global chi-square 13.07 vs. 8.65; P=0.04).Conclusions: Data from the present study demonstrated the importance of FGF21 as a potential biomarker that may reflect a different pathophysiologic implication from natriuretic peptides.