Circulating fibroblast growth factor-21 in coronary artery disease: a systematic review and meta-analysis

Fibroblast growth factor-21 (FGF21) is a metabolic regulator involved in glucose and lipid homeostasis and has emerged as a potential biomarker in cardiometabolic diseases. The relationship between circulating FGF21 levels and coronary artery disease (CAD) remains unclear. We performed a systematic review and meta-analysis to clarify this association and assess its clinical relevance.

PubMed, Web of Science, and Scopus were searched for observational studies reporting circulating FGF21 levels in adult CAD patients. Standardized mean differences (SMDs) with 95% confidence intervals were calculated using a random-effects model. Subgroup and meta-regression analyses were conducted to explore heterogeneity.

Fourteen studies including 2963 CAD patients were analyzed. Circulating FGF21 levels were significantly higher in CAD patients than in controls (SMD = 0.90; 95% CI: 0.26-1.54; p = 0.0056). In acute CAD, the increase was more pronounced (SMD = 1.70; 95% CI: 0.20-3.21). Elevated FGF21 persisted even when diabetes prevalence was low (SMD = 1.50; 95% CI: 0.15-2.84). Meta-regression identified BMI and HDL as independent contributors to inter-study variability. Sensitivity analyses confirmed robustness, and no strong evidence of publication bias was detected.

Circulating FGF21 is elevated in CAD, primarily reflecting metabolic disturbances-particularly adiposity and dyslipidemia-rather than diabetes or CAD itself. Levels tend to be higher during acute events, suggesting that FGF21 may serve as a marker of metabolic stress and lipid abnormalities rather than a direct diagnostic biomarker.