CERT2 Improves Cardiovascular Risk Prediction Over Standard Tests

JUNE 24, 2019
Patrick Campbell
Doctor with patientA recent study has found that a ceramide- and phospholipid-based risk score, not LDL cholesterol (LDL-C), can efficiently predict residual cardiovascular disease (CVD) event risk in patients with coronary heart disease (CHD). 

While investigators concluded that ceramide-phospholipid risk score showed comparable and synergistic predictive performance when compared with previously published CVD risk models, they also found that there was variability in the risk of CVD events in patients with coronary artery disease.

“It is common to assume that all CHD patients have an equivalent cardiovascular risk, but according to this study this seems not to be the case. For instance, the 10-year cardiovascular death risk of a CHD patient may vary from 5% to over 20%,” said Reijo Laaksonen, MD, PhD, chief medical officer for Zora Biosciences.

The 3 studies that investigators pooled data from were the Western Norway Coronary Angiography Cohort (WECAC), the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial, and Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung (KAROLA). Analyses were performed for CV death and a composite CV event endpoint that included CV death, myocardial infarction, and stroke. Investigators used 4 established ceramide molecules and ceramide ratios, as well as 12 phospholipids that predicted CV events in the WECAC study. 

Based on those variables, investigators created a 0-12 point risk score system by giving points based on population quartiles for the variables. Based on their scores, individuals were divided into 4 risk categories. 

Investigators sought to determine whether they could improve the ceramide test score (CERT1) by adding certain PCs. The new test score, named CERT2, had one ceramide/ceramide ratio, two ceramide/PC ratios, and a single PC. Investigators found that, in general, the ceramide-PC ratio components of CERT2 showed significantly higher than previously published ceramide-ceramide ratios across all 3 studies. 

The multi adjusted hazard ratios for predicting CVD mortality in each group were as follows: 1.44 (1.28–1.63) in WECAC, 1.47 (1.34–1.61) in the LIPID trial, and 1.69 (1.31–2.17) in KAROLA. Investigators also found a combination of the risk score with high-sensitivity troponin T increased hazard ratios to 1.63 and 2.04 in WECAC and KAROLA cohorts, respectively.

Additionally, the C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. Investigators noted that the ceramide-phospholipid risk score was comparable and synergistic predictive performance compared with previously published CVD risk models for secondary prevention. 

Within their conclusion, authors wrote that CERT2 scores offer an easy to use tool for estimation residual risk in patients with CHD. Adding that the tool could be used to further improve development of personalized management of CHD — which has the potential to be used in future prospective studies.

This study, titled “Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients,” was published in the European Heart Journal.

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