A new plasma ceramide 24-based risk score predicts overall mortality and nonfatal myocardial infarction in patients with suspected or known coronary artery disease

Background and aim: Plasma ceramides (Cer) are associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD). We examined whether a newly developed plasma ceramide-based risk score (CER24 score) performs better than CERT1 risk score in predicting adverse cardiovascular outcomes in patients with known or suspected CAD. Methods and results: We followed 167 ambulatory patients undergoing stress myocardial perfusion scintigraphy (MPS) for clinical reasons for a median of 6 years. For the CER24 risk score calculation, we measured plasma Cer(d16:1/24:1)/Cer(d16:1/24:0), Cer(d18:0/24:1)/Cer(d18:0/24:0), Cer(d18:1/24:1)/Cer(d18:1/24:0), Cer(d18:2/24:1)/Cer(d18:2/24:0), and Cer(d20:1/24:1)/Cer(d20:1/24:0), both before and after stress MPS, using a targeted liquid chromatography-tandem mass spectrometry assay. Pre-stress CER24 risk categories (high vs. low/moderate risk) at baseline were associated with a ∼3-fold higher risk of developing the primary composite outcome (defined as all-cause mortality or nonfatal myocardial infarction) even after adjustment for age, sex, smoking, diabetes, pre-existing CAD, left ventricular ejection fraction, and stress-induced inducible myocardial ischemia on MPS (adjusted-hazard ratio 3.06, 95 %CI 1.63-5.77; p = 0.001). Post-stress CER24 risk categories yielded similar results. CER24 high-risk category performed better than CERT1 high-risk category in predicting the primary composite outcome (AUCs = 0.647 vs. 0.580; p = 0.048). Conclusions: The CER24 score is associated with a higher risk of the composite outcome and performs better than CERT1 score in predicting the risk of dying or developing nonfatal cardiovascular events.