A combined biomarker panel of IP-10, MCP-1, and sST2 achieves high diagnostic accuracy for troponin-negative obstructive coronary artery disease

Background: Ischemic heart disease (IHD) remains a leading cause of global mortality, with early diagnosis being critical for effective intervention. Traditional biomarkers, such as troponin, are elevated primarily in irreversible myocardial necrosis. This study evaluated the diagnostic accuracy of four candidate inflammatory and remodelling biomarkers - IP-10, MCP-1, sST2, and IL-18 - for detecting troponin-negative obstructive CAD before biomarker evidence of myocyte death. Methods: In a prospective case-control study, 140 patients with angiographically confirmed troponin-negative obstructive CAD (unstable angina with normal high-sensitivity troponin I) and 70 ageand sex-matched healthy controls were enrolled. Serum concentrations of IP-10, MCP-1, sST2, and IL-18 were measured using multiplex bead-based immunoassays. Logistic regression was used to develop a multi-marker model, and its performance was assessed via the area under the receiver operating characteristic curve (AUC). Results: Serum levels of all four biomarkers were significantly higher in the IHD group than in controls (p<0.001 for all). In the final multivariable model, the three-marker panel of IP-10, MCP-1, and sST2 provided the highest diagnostic accuracy, whereas IL-18 did not add independent discriminatory value. The final panel achieved an AUC of 0.94 (95% CI 0.90-0.97), with 89.3% sensitivity and 87.1% specificity at the optimal cut-point. Conclusion: A three-marker biomarker panel composed of IP-10, MCP-1, and sST2 demonstrated excellent diagnostic performance for troponin-negative obstructive CAD. These inflammationand stress-related remodelling proteins may help identify patients with significant coronary disease before irreversible myocardial injury, although external validation is required.