Abstract
BACKGROUND: Coronary artery calcification (CAC) is a strong predictor of long-term adverse outcomes in patients with coronary artery disease (CAD). Meanwhile, insulin resistance (IR) is a key metabolic disorder that accelerates CAC progression through multiple pathways. Fibroblast growth factor 21 (FGF21) improves glucolipid metabolism and has been associated with vascular calcification. However, the relationship between serum FGF21 level and CAC severity in patients with varying degrees of IR remains unclear. METHODS: A total of 128 patients with CAD who underwent preprocedural coronary computed tomography angiography and percutaneous coronary intervention were enrolled. Patients were stratified by triglyceride-glucose (TyG) index into high (TyG >8.62, n = 62) and low (TyG ≤8.62, n = 66) groups. Associations between FGF21 levels and severe CAC were analyzed under varying degrees of IR. RESULTS: In patients with a TyG index >8.62, serum FGF21 levels were significantly lower in those with severe CAC, and were negatively correlated with CAC scores. Multivariable analysis revealed that serum FGF21 levels were independently associated with severe CAC (odds ratio (OR) per 1-standard deviation (SD) increase: 0.261; 95% confidence interval (CI): 0.073, 0.933; p < 0.05). In contrast, serum FGF21 levels among patients with a TyG index ≤8.62 did not differ significantly between the severe and non-severe CAC groups, and no independent association between serum FGF21 level and severe CAC was observed after adjustment. Importantly, a significant interaction was observed between the TyG index and FGF21 level (p for interaction = 0.035). Moreover, the protective association between FGF21 and CAC was primarily observed in patients with a high TyG index. CONCLUSIONS: Lower serum FGF21 levels in patients with CAD can identify individuals at increased risk of severe CAC, particularly among those with a higher degree of IR. Serum FGF21 levels may serve as a novel biomarker for CAC risk stratification in metabolically susceptible patients.