CERT2 ceramide- and phospholipid-based risk score and major adverse cardiovascular events: A systematic review and meta-analysis

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.