Abstract 15349: Circulating Glycosphingolipids Primarily Correlate With LDL-C but Not HDL-C or TG and Are Associated With Disease Severity in Acute Myocardial Infarction

Introduction: Circulating cholesterol remains a principal target of therapies aimed at reducing ischemic events after acute myocardial infarction (AMI). Studies have shown that sphingolipids, a class of non-cholesterol lipids, may have pro-atherogenic properties. Hypothesis: We hypothesized that specific sphingolipid species correlate with cholesterol lipoprotein fractions in AMI and that such associations may identify sphingolipid species with atherogenic and prognostic potential. Methods: Using quantitative tandem mass spectrometry, we measured 91 sphingolipid species, including 18 ceramides (Cer), 16 dihydroCer, 11 sphingomyelins, 12 dihydrosphingomyelins and 34 glycosphingolipids (GSLs) in plasma from 621 AMI patients. Statistical methods, including Kendall’s Tau correlation analysis, were used to investigate the correlation of circulating sphingolipids with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and with triglycerides (TG). Results: The median age of patients was 58 (52-66) and 17.8% were women. Sphingolipid species that positively correlated with all 3 lipoproteins included sphingomyelins (C22:1, C20:0), dihydrosphingomyelins (C14:0, C18:2) and Cer C14:0. Unexpectedly, the majority of the GSLs, namely LacCer d18:1/16:0, GlcCer d18:1/22:0 and 24:0, were positively correlated only with LDL-C (r > 0.30, FDR Conclusions: In patients with AMI, among the classes of circulating sphingolipids, GSLs were significantly associated with LDL-C but not HDL-C or TG and were enriched among patients with STEMI as compared with non-STEMI. Further studies should be undertaken to explore the potential role of GSLs in the atherogenic effects LDL-C and in modulating the severity of the AMI phenotype.