Outcomes trials
Plasma CETP, alongside EPCR, is an independent MACE risk factor in older men with chronic coronary syndrome and improves on the Framingham score (Front Cardiovasc Med 2022)
Original title: Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome
A study profiled plasma proteomics in 38 patients with chronic coronary syndrome, 19 who went on to have a major adverse cardiovascular event (MACE) and 19 who did not, using data-independent acquisition mass spectrometry and a machine-learning pipeline to shortlist candidate biomarkers. Fifty-seven differentially expressed proteins were identified, and three candidates were carried forward for validation by ELISA in an independent prospective cohort. Endothelial protein C receptor (EPCR) and CETP levels at admission were significantly higher in patients who later had a MACE than in those who did not, while carboxypeptidase B2 levels did not differ. In Cox survival analysis, both EPCR and CETP were independent MACE risk factors, and a prognostic model combining the Framingham coronary heart disease risk score with EPCR and CETP levels improved MACE prediction over the Framingham score alone.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.