Abstract
BACKGROUD: Biomarker discovery remains pivotal for improving coronary artery disease (CAD) and acute myocardial infraction (AMI) diagnosis. While interferon-induced transmembrane proteins (IFITM1/2/3) are established in viral defense and cancer progression, their roles in cardiovascular pathologies are undefined. METHODS: A retrospective cohort study was conducted, including a discovery cohort (129 CAD patients and 20 controls), a validation cohort (40 CAD patients and 16 controls) and a third cohort of 52 patients with acute myocardial infraction (AMI). Serum IFITM1/2/3 levels were specifically quantified using enzyme linked immunosorbent assay (ELISA). Coronary stenosis severity was assessed using the Gensini score. The evaluation of diagnostic performance utilized receiver operating characteristic (ROC) curves, whereas Spearman's rank test facilitated the analysis of correlations. RESULTS: Compared with controls, CAD patients exhibited significantly elevated serum IFITM1/2/3 levels (p < 0.001). ROC analysis demonstrated exceptional diagnostic accuracy for CAD detection: IFITM1 (AUC 0.9375, sensitivity 95%, specificity 81.25%), IFITM2 (AUC 0.8984, sensitivity 90%, specificity 75%), and IFITM3 (AUC 1.000, sensitivity 97.5%, specificity 100%). IFITM levels were significantly positively correlated with Gensini scores (p < 0.0001), indicating a plaque burden-dependent expression pattern. AMI patients exhibited further elevation of IFITM1/2/3 compared to patients with stable CAD (p < 0.0001), with IFITM1 specifically upregulated in AMI with heart failure (3.07 vs. 4.64 ng/mL, p = 0.003). CONCLUSION: IFITM1/2/3 may serve as novel serum biomarkers for diagnosing CAD and AMI, as well as stratifying coronary stenosis severity, with high discriminatory capacity. Our findings position IFITMs as promising tools for precision cardiovascular risk assessment and therapeutic targeting.