The clinical significance of serum complement fibroblast growth factor 21 in patients with rheumatoid arthritis

OBJECTIVE: This study aimed to assess serum fibroblast growth factor 21 (FGF-21) levels and explore their clinical significance in patients with rheumatoid arthritis (RA). METHODS: A total of 187 patients with RA, who were treated at Xuzhou Central Hospital between January 2023 and December 2024, were enrolled in this study. Based on carotid intima-media thickness (cIMT) measurements, they were categorized into a plaque group (n = 118) and a plaque-free group (n = 69). Additionally, 139 healthy individuals undergoing routine physical examinations were recruited as healthy controls (HC). Clinical data were collected from all participants, including lipid profiles, HOMA-IR, ESR, CRP, RF, anti-CCP antibody levels, and serum FGF-21 concentrations. We analyzed the associations between serum FGF-21 levels and both disease activity and atherosclerotic status in RA patients. Statistical analyses, including the chi-square test, Student's t-test, Pearson correlation analysis, and logistic regression, were performed to evaluate these relationships. RESULTS: Serum levels of FGF-21 were significantly elevated in patients with RA compared with healthy controls (805.7 ± 188.68 vs. 203.8 ± 50.7 pg/mL, p < 0.001). Among RA patients, those with carotid plaques exhibited higher FGF-21 levels than those without plaques (840.7 ± 203.6 vs. 745.6 ± 142.2 pg/mL, p < 0.001). Correlation analyses revealed that serum FGF-21 levels were positively associated with LDL-C (r = 0.544), HOMA-IR (r = 0.625), anti-CCP antibodies (r = 0.617), rheumatoid factor (r = 0.366), DAS28 (r = 0.309), and cIMT (r = 0.604) (all p < 0.001). Conversely, FGF-21 levels were negatively correlated with the use of disease-modifying antirheumatic drugs (DMARDs) (r = - 0.569, p < 0.001) and flow-mediated dilation (FMD) (r = - 0.294, p < 0.001). Multivariate logistic regression analysis identified the serum FGF-21 level as an independent factor associated with increased cIMT (odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.001-1.006, p = 0.006). CONCLUSIONS: Our findings suggest a potential correlation between elevated FGF-21 levels and RA disease activity as well as certain metabolic parameters. Further replication studies are needed to clarify whether FGF-21 might serve as a research biomarker in the context of cardiovascular comorbidity in RA.