Ceramide-based risk score CERT-1 improves risk prediction for overall mortality and adverse cardiovascular outcomes in patients with and without cardiovascular disease: A prospective cohort study

Whether the plasma-based ceramide-based risk score CERT1 improves risk prediction for cardiovascular disease (CVD) is uncertain. Baseline and follow-up data were combined from two cohorts, 334 patients with established/suspected CVD and 196 patients with type 2 diabetes followed for a median of 74 months (interquartile range 54-79 months). For the calculation of CERT1 risk score, we measured four specific plasma ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1)] and their ratios to Cer(d18:1/24:0). Based on the CERT1 risk score, patients were split into four risk categories (low, moderate, increased or high risk). The primary outcome was a composite of overall mortality and incident nonfatal CVD outcomes (including myocardial infarction, ischaemic stroke or permanent atrial fibrillation). One hundred and thirty-nine patients developed the primary composite outcome (72 nonfatal CVD outcomes and 67 total deaths) during follow-up. Baseline CERT1 risk categories were significantly associated with the risk of developing the primary composite outcome (adjusted HR for high vs. low-risk category 2.43, 95% CI 1.39-4.22, p = 0.002, and adjusted HR for increased vs. low-risk category 2.16, 95% CI 1.28-3.63, p = 0.004). Receiver operator characteristic curve analysis showed that adding CERT1 risk score to traditional CVD risk factors and pre-existing CVD, improved the discriminatory capability of the regression model for predicting the primary composite outcome (AUROC 0.691 [95% CI 0.674-0.769] vs. 0.722 [95% CI 0.642-0.742], p = 0.0275). The ceramide-based risk score CERT1 risk score improves risk prediction for long-term risk of overall mortality and adverse cardiovascular outcomes in patients with and without CVD.