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

Abstract

Fanghui Li,1,2,* Dongze Li,1,* Jing Yu,1 Yu Jia,3 Jirui Wen,4 Wentao Li,2 Yao Tong,2 Jiang Wu,4 Zhi Wan,1 Yu Cao,1 Qing Zhang,2 Rui Zeng1,2 1Department of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of General Practice and National Clinical Research Center for Geriatrics, International Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Zeng; Qing Zhang, Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: 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.Keywords: ceramide, acute coronary syndrome, mortality, high-performance liquid chromatography with tandem mass spectrometry

Keywords

• ceramide
• acute coronary syndrome
• mortality
• high-performance liquid chromatography with tandem mass spectrometry