Circulating FNDC4 levels and 12-month major adverse cardiovascular events in patients with STEMI undergoing PCI: A prospective cohort study.

Fibronectin type III domain-containing protein 4 (FNDC4) is a circulating hepatokine with anti-inflammatory and cardioprotective properties, but its prognostic relevance after ST-segment elevation myocardial infarction (STEMI) remains uncertain. We investigated whether admission serum FNDC4 levels were associated with 12-month major adverse cardiovascular events (MACE) in patients with STEMI undergoing primary or urgent percutaneous coronary intervention (PCI). This single-center prospective observational study included 274 patients. Serum FNDC4 was measured before PCI using an enzyme-linked immunosorbent assay, and participants were followed for 12 months. Associations and prognostic performance were assessed using Spearman correlation, receiver operating characteristic, Kaplan-Meier, and Cox proportional hazards analyses. During follow-up, 51 patients (18.6%) experienced MACE. Serum FNDC4 levels were significantly lower in patients with MACE and were inversely correlated with interleukin-6 (IL-6) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The area under the receiver operating characteristic curve (AUC) for FNDC4 was 0.771 (95% confidence interval [CI], 0.695-0.839). Adding FNDC4 to a clinical model increased the AUC from 0.874 to 0.905 (ΔAUC, 0.031; 95% CI, 0.009-0.061). After adjustment for age, NT-proBNP, left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and Killip class III/IV, each 10 ng/mL decrease in FNDC4 was associated with a higher risk of MACE (hazard ratio, 1.821; 95% CI, 1.360-2.438; p<0.001). Lower admission FNDC4 levels were independently associated with 12-month MACE after PCI for STEMI and may provide complementary prognostic information; however, multicenter external validation and serial FNDC4 measurements are required before clinical application.