Abstract
BackgroundCoronary 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.MethodsFive 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.ResultsAfter 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.ConclusionThe 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.
Highlights
Coronary artery stenosis induces heart diseases including acute coronary syndrome (ACS)
In model 1, the results show that high level of Cer (d18:1/24:1)/Cer (d18:1/24:0) (odds ratio (OR) 18.927, 95% confidence interval (CI) 1.902–188.380), female gender, high level of HbA1c% and acute myocardial infarction (AMI) compared with atherosclerosis were associated with more severe coronary artery stenosis (Table 2)
After clinical risk factors adjustment including concentrations of targeted ceramides, stenosis severity, infarction history, diagnosis during index hospitalization, gender, age, smoking, and HbAc1% inmultiple logistic regression model, the results showed that pre-existing infarction history was associated with major adverse cardia and cerebrovascular events (MACE), whereas stenosis severity and other factors were not
Summary
Coronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). In the past few years, numerous studies have suggested that ceramides and other sphingolipids regulate cellular responses to extracellular stimuli and stress and they are involved in pathophysiological mechanism in many disease areas [3,4,5,6] It has been proposed and confirmed by several researchers [7, 8] that plasma ceramide level increased drastically in the presence of high level of LDL cholesterol. The plasma ceramides that have been studied as high-risk factors are Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) and the ratios of these ceramides to Cer (d18:1/24:0) [15, 16] These studies suggest that plasma ceramide may contribute to atherogenesis and correlate with the risk of coronary heart disease, the solid clinical evidence indicating the association between the plasma ceramides and the coronary artery stenosis and the incidence of ACS is still inadequate
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