Enhanced risk stratification for hard CVD outcomes: Integrating CERT2 with coronary artery calcium assessment in the MESA cohort

Abstract Background Coronary artery calcium (CAC) scoring is an established tool for coronary heart disease risk stratification. Recently, the CERT2 score—based on ceramides and phospholipids—has emerged as a promising biomarker for predicting cardiovascular disease (CVD) outcomes. Purpose This study investigates whether incorporating the CERT2 score alongside CAC scoring enhances the prediction of hard CVD outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods We conducted a retrospective analysis of the MESA cohort (n=5849), stratifying subjects according to their CAC scores and CERT2 values. The CERT2 score was categorized into two groups: low risk (0–9 points) and high risk (10–12 points). Participants were further segmented by CAC score into four categories: 0, 1–100, 101–300, and 300. The primary endpoint was hard CVD outcomes, with hazard ratios (HR) calculated using Cox proportional hazards models and adjustments made for traditional risk factors. Results In the overall cohort, a high CERT2 score was significantly associated with an increased risk of hard CVD outcomes (HR = 1.87, p 0.0001). In the CAC 1–100 group, subjects with a high CERT2 score experienced a significantly higher 10-year event rate, with an HR of 2.13 (p = 0.003). Similarly, in the CAC 101–300 group, a high CERT2 score was associated with an increased risk of hard CVD events (HR = 2.04, p = 0.024). In the CAC 300 group, the HR was 1.96 (p = 0.013), whereas in the CAC = 0 group the HR was 1.37 (p=ns). Conclusion The integration of the CERT2 score with CAC assessment provides a more granular approach to risk prediction. A high CERT2 score appears to reclassify subjects into a higher risk category, potentially supporting more tailored therapeutic interventions