Association between ceramides and coronary artery stenosis in patients with coronary artery disease

Abstract

Background: Coronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome. Methods: Five hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk. Results: After the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/ cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642-0.822. Conclusion: The severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.

Emerging Roles of Ceramide in Cardiovascular Diseases

“…The main types of ceramides with increased abundance are C16, C20, C20:1, and C24 [ 50 ]. They are positively correlated with plaque rupture and the severity of coronary artery stenosis in patients with STEMI [ 56 , 57 ]. Therefore, ceramide is used as a biomarker and an independent diagnostic indicator in the prognosis of acute myocardial infarction and has been proven to have great potential in combination with high-sensitivity troponin T in identifying patients with acute coronary syndrome [ 58 ].…”

The Complex Tail of Circulating Sphingolipids in Atherosclerosis and Cardiovascular Disease

“… 110 The reason for the correlation between plasma ceramides and CVD is not totally understood, but many CVD events are a direct result of coronary artery stenosis, which is associated with the same ceramide score as above. 111 The ceramide score is slowly being introduced into clinical practice. 112 …”

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

“…Recent studies have highlighted the potential use of circulating ceramides as novel biomarkers in the development and progression of CVD, as they can have more predictive value than LDL cholesterol [62][63][64]. Their role as novel biomarkers is also investigated in cardiovascular related diseases, such as type-2 diabetes, IR, or obesity [65][66][67]. Ceramides can not only assess the risk of cardiac events but also can provide additional information regarding the cardiovascular risk in patient populations with certain predisposing conditions [68][69][70].…”