Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome

BACKGROUND: Chronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification. METHODS: Data-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay in an independent prospective cohort. RESULTS: Fifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone. CONCLUSION: Plasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS.