Prognostic significance of plasma molecular lipid species in coronary artery disease patients: A prospective cohort study

Abstract Background Circulating plasma lipids are vital indicators for quantifying coronary artery disease (CAD) risk, yet traditional biomarkers like LDL, HDL, and triglycerides often exhibit limited predictive capacity. Advancements in lipidomics have identified novel molecular constituents with the potential to improve prognostication in CAD patients. However, the prognostic value of lipidomics for long-term mortality has not yet been investigated. Objective In our study, which was part of the European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis (ATHEROREMO), we aimed to investigate the predictive value of specific molecular lipid species for long-term mortality. Methods We utilized data from the 581 CAD patients enrolled in the ATHEROREMO clinical imaging study, who were admitted for either diagnostic coronary angiography or percutaneous coronary intervention. We measured a series of serum lipid species, comprising ceramides (Cer) and cholesteryl esters (CE), by mass spectrometry-based shotgun lipidomics. Long-term all-cause mortality follow-up was conducted in 2022 via the Civil Registry. We used the Kaplan-Meier method and multivariable Cox-proportional hazards regression (correction for age, sex, cardiac risk factors, statin use, hypercholesterolemia, and angiography indication) to assess survival distributions and associations with all-cause mortality. Results Mean age was 61.5 years (IQR: 53.5-61.5), 75% were male. A total of 55% patients were diagnosed with acute coronary syndrome (ACS) and 45% with stable angina pectoris (SAP). During a median follow-up of 11 years (IQR: 10.1-13.4) 179 patients died. Five molecular lipid species (two cholesteryl esters, one ceramide and two ceramide ratios) correlated with mortality (see Table). As an example, Figure 1 demonstrates a clear survival difference between patients with Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio below versus above the median. Findings were consistent for ACS and SAP. Conclusion Our study demonstrates the prognostic value of specific cholesteryl esters, ceramides and ceramide ratios for 11-year mortality in patients with CAD. To the best of our knowledge, this is the longest follow-up study so far within this domain.Table.Lipid molecule and Mortality 11-yFig.1 Kaplan Meier Ceramide ratio