Abstract 4369679: Plasma Protein Biomarkers of Coronary Artery Ectasia Based on Multiple Cohort Studies

Abstract

Background: Coronary artery ectasia (CAE), defined as pathological coronary dilation exceeding 1.5 times the diameter of adjacent normal segments, is a complex cardiovascular disorder. Its pathogenic mechanisms remain incompletely understood, and non-invasive diagnostic tools are currently limited. Methods: Plasma proteomic profiles from a Chinese cohort (analyzed by data-independent acquisition (DIA)) were integrated with UK Biobank data (Olink Explore platform) to identify CAE-specific biomarkers. Cross-platform meta-analysis identified consistently dysregulated proteins. Four candidate biomarkers were subsequently validated using enzyme-linked immunosorbent assay (ELISA) in independent cohorts. Results: We identified CAE-associated biomarkers enriched in pathways involving immune activation, extracellular matrix remodeling, and cytokine signaling. Meta-analysis revealed nine consistently dysregulated proteins. Four biomarkers were validated as reliable diagnostic tools: cluster of differentiation 27 (CD27), C-X-C motif chemokine ligand 14 (CXCL14), Insulin-like growth factor-binding protein 7 (IGFBP7), and Lipopolysaccharide-binding protein (LBP). These demonstrated robust diagnostic performance (area under the curve [AUC] range: 0.70–0.90), correlated significantly with disease severity, and were markedly elevated in CAE patients complicated by myocardial infarction. The findings implicate chronic low-grade vascular inflammation and T-cell immune dysregulation as potential pathogenic mechanisms driving CAE progression. Conclusion: This study identifies novel non-invasive biomarkers (CD27, CXCL14, IGFBP7, LBP) for the early detection and risk stratification of CAE, addressing critical gaps in clinical management. The results establish key pathogenic pathways driving CAE progression.