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Accumulating evidence over the last decade suggests the promising role of ceramides as potential mediators of coronary artery disease (CAD) or prognostic biomarkers of its clinical course. This meta-analysis (CRD42021241058) aimed to assess the prognostic value of a ceramide- and phosphatidylcholine-based risk score, Coronary Event Risk Test 2 (CERT2) score, for the prediction of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction or stroke) in 26,896 individuals with established CAD. Patients with CERT2=0-3 were used as a reference group. Pooled risk ratio (RR) of MACE among patients with CERT2=4-6 was equal to 1.35 (95% confidence intervals, CI: 1.11-1.64). Patients with CERT2=7-8 had an 81% increased risk of MACE (RR=1.81, CI: 1.40-2.34), while those with CERT2=9-12 had a 165% increased risk of MACE (RR=2.65, CI: 1.85-3.80). Subgroup analysis in patients with chronic coronary syndrome yielded an adjusted hazard ratio for MACE equal to 1.20 (CI: 1.09-1.32) per one standard deviation increase of CERT2 score. A summary c-statistic of the score combined with classical risk assessment model was found equal to 0.68 (95% CI: 0.58 to 0.77; approximate 95% prediction interval 0.38 to 0.88). Therefore, CERT2 score seems to emerge as a robust predictor of MACE. However, additional research is warranted to establish the cost-effectiveness of CERT2 score calculation for the determination of residual risk in patients with CAD.

The GRACE score constitutes a useful tool for risk stratification in patients with acute coronary syndrome (ACS), while the SYNTAX score determines the complexity of coronary artery disease (CAD). This study sought to correlate these scores and assess the accuracy of the GRACE score in predicting the extent of CAD. A total of 539 patients with ACS undergoing coronary angiography were included in this analysis. The patients were classified into those with a SYNTAX score &lt, 33 and a SYNTAX score ≥ 33. Spearman’s correlation and receiver operator characteristic analysis were conducted to investigate the role of the GRACE score as a predictor of the SYNTAX score. There was a significantly positive correlation between the SYNTAX and the GRACE scores (r = 0.32, p &lt, 0.001). The GRACE score predicted severe CAD (SYNTAX ≥ 33) moderately well (the area under the curve was 0.595 (0.522–0.667)). A GRACE score of 126 was documented as the optimal cut-off for the prediction of a SYNTAX score ≥ 33 (sensitivity = 53.5% and specificity = 66%). Therefore, our study reports a significantly positive correlation between the GRACE and the SYNTAX score in patients with ACS. Notably, NSTEMI patients with a high-risk coronary anatomy have higher calculated GRACE scores. A multidisciplinary approach by a heart team could possibly alter the therapeutic approach and management in patients presenting with ACS and a high calculated GRACE score.