Association Between Plasma Ceramides and One-Year Mortality in Patients with Acute Coronary Syndrome: Insight from the PEACP Study

Abstract

Background The plasma lipidome profile is likely to improve risk stratification in patients with acute coronary syndrome (ACS) and predict cardiovascular events for secondary disease prevention. Ceramides are involved in the initiation or acceleration of several key pathophysiological processes in atherosclerosis. This study evaluated whether plasma ceramide levels at admission was associated with one-year mortality in patients with ACS. Methods In total, 826 patients with ACS from a prospective multicenter study for early evaluation of acute chest pain were enrolled. High-performance liquid chromatography with tandem mass spectrometry (LC/MS) was used to measure the plasma levels of eleven ceramides (C16–C26). The primary outcome was all-cause mortality, and the secondary outcome was cardiac mortality during the one-year follow-up. The relationship between the ceramide levels and mortality was evaluated by Cox regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate discrimination of ceramides. Results Eighty-eight (10.7%) patients died after a 12-month follow-up. Five ceramides (C16:0, C18:0, C20:0, C24:1 and C24:2) and their ratios to Cer(d18:1/24:0) were independently associated with the risk of all-cause death and cardiac death. Combining the Global Registry of Acute Coronary Events (GRACE) score with ceramides and their ratios to Cer(d18:1/24:0) had areas under ROC curves ranging from 0.778–0.804 (P<0.001) for all-cause mortality, which was greater than that of the GRACE score alone. Conclusion Measurements of long-chain ceramides and very-long-chain ceramides may help in identifying a high risk of mortality beyond traditional assessment tools in patients with ACS. Trial Registration clinicaltrials.gov, identifier: NCT04122573.

Lipidomic-Based Algorithms Can Enhance Prediction of Obstructive Coronary Artery Disease

“…Long-chain and very-long-chain ceramides have also emerged as potential markers for increased mortality risk in ACS, surpassing the limitations of conventional assessment tools. 49 PCs constitute a class of phospholipids distinguished by diverse fatty acid chains tethered to the glycerol backbone, playing a pivotal role in signaling, inflammation, and providing energy substrates. Serving as essential energy storage depots, these molecules undergo enzymatic degradation, cleaving the ester bond between the glycerol backbone and releasing fatty acids, alongside LPC.…”

“…Notably, Cer 18:1;O2_18:0, Cer 18:1;O2_24:1, and GlcCer 18:1;O2_16:0 emerged as particularly significant biomarkers, identified by the XGBoost algorithm, with a high predictive value for SS > 0. Long-chain and very-long-chain ceramides have also emerged as potential markers for increased mortality risk in ACS, surpassing the limitations of conventional assessment tools …”