Basal and post-stress ceramide-based risk score CERT1 predicts all-cause mortality and nonfatal myocardial infarction in patients with suspected or established coronary artery disease undergoing stress myocardial perfusion scintigraphy

Background and aim: We examined whether a plasma ceramide-based risk score (CERT1 score), a newly proposed tool for cardiovascular risk prediction, is associated with an increased risk of all-cause mortality and nonfatal myocardial infarction in patients with suspected or known coronary artery disease (CAD). Methods and results: We studied 167 ambulatory patients who consecutively underwent stress myocardial perfusion scintigraphy (MPS) for clinical reasons in 2017 (at baseline) and then followed for a median of 6 years (inter-quartile range: 4.7–6.6 years). For the calculation of the CERT1 score, both before and after stress MPS, we measured three specific plasma ceramide concentrations [Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1)] and their ratio to Cer(d18:1/24:0) using a targeted liquid chromatography-tandem mass spectrometry assay. The primary outcome of the study was a composite of all-cause mortality or nonfatal myocardial infarction. During a median of 6 years, a total of 50 events occurred (26 all-cause deaths and 24 nonfatal myocardial infarctions). There was a significant association between pre-stress CERT1 risk categories (high vs. low risk) at baseline and the risk of developing the primary composite outcome (unadjusted HR 1.78, 95% CI 1.02–3.14). This risk remained significant after adjustment for age, sex, smoking, diabetes, pre-existing CAD, left ventricular ejection fraction, and stress-induced inducible myocardial ischemia on MPS (adjusted HR 2.28, 95% CI 1.17–4.41, p = 0.015). Almost identical results were observed for post-stress CERT1 risk categories. Conclusions: Pre-stress and post-stress CERT1 high-risk categories at baseline were strongly associated with an increased long-term risk of all-cause mortality or nonfatal myocardial infarction in patients with suspected or established CAD.