We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI). Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature's 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature.
Keywords: AMI, acute myocardial infarction; CABG, coronary artery bypass graft; CAD, coronary artery disease; CerS6, ceramide synthase 6; DDg, data-driven grouping; HILIC, hydrophilic interaction LC; LAD, left anterior descending; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction; SPT, serine palmitoyl transferase; SPTLC2, serine palmitoyl transferase-2; SWVg, statistically-weighted voting grouping; acute coronary syndrome; ceramides; dihydroceramides; major adverse cardiovascular and cerebrovascular events; nSMase, neutral sphingomelinase; prognosis; risk prediction.