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

Chenchen Tu, Lan Xie, Zhenjie Wang, Lili Zhang, Hongmei Wu, Wei Ni, Caixia Li, Lin Li, Yong Zeng, Chenchen Tu, Lan Xie, Zhenjie Wang, Lili Zhang, Hongmei Wu, Wei Ni, Caixia Li, Lin Li, Yong Zeng

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.

Keywords: Acute coronary syndrome; Acute myocardial infarction; Ceramide; Coronary stenosis; Liquid chromatography-tandem mass spectrometry; Major adverse cardiac and cerebrovascular events.

Conflict of interest statement

No conflicts of interest, financial issue or other issues are declared by the authors.

Figures

Fig. 1
Fig. 1
Work flow of the study
Fig. 2
Fig. 2
The representative image of coronary artery stenosis
Fig. 3
Fig. 3
Concentration of ceramides and ratio of ceramides to cer (d18:1/24:0). a. concentration of cer (d18:1/16:0) and cer (d18:1/18:0): there were no significant differences in cer (d18:1/16:0) or cer (d18:1/18:0) level between groups. b. concentration of cer (d18:1/24:1) and cer (d18:1/24:0): neither cer (d18:1/24:1) nor cer (d18:1/24:0) were significantly different between groups. c. ratio of ceramides to cer (d18:1/24:0): ratio of cer (d18:1/16:0) to cer (d18:1/24:0) was significantly increased in group with stenosis < 25% compared to group with stenosis 25–50% (P < 0.05), whereas there was no difference between other groups. There were no significant differences in ratios of cer (d18:1/18:0) or cer (d18:1/24:1) to cer (d18:1/24:0) between groups. (data is presented as mean ± SEM)
Fig. 4
Fig. 4
Level of plasma ceramide species in ACS and atherosclerosis patient: a. concentration of cer (d18:1/16:0) and cer (d18:1/18:0): cer (d18:1/16:0) concentration wasonly significantly elevated in AMI compared to those in UAP (P < 0.05), whereas there was no different concentration of cer (d18:1/18:0) observed between groups. b. concentration of cer (d18:1/24:1) and cer (d18:1/24:0): there was no difference in cer (d18:1/24:1) concentration between groups, whereas cer (d18:1/24:0) concentration was significant increased in AMI compared to it in UAP and no difference compared to it in atherosclerosis(**P < 0.01). c. ratio of ceramides: there was only a significant increased ratio of cer (d18:1/24:1)/cer (d18:1/24:0) in AMI compared to it in UAP (P < 0.05). (data is presented as mean ± SEM)
Fig. 5
Fig. 5
Concentration of ceramides and ratio of ceramides to cer (d18:1/24:0): There was a significant increased ratio of cer (d18:1/24:1)/cer (d18:1/24:0) in group of stenosis > 50% compared to group of stenosis P < 0.05), whereas no difference was observed in other ceramides and ratios of ceramides between groups. (data is presented as mean ± SEM)
Fig. 6
Fig. 6
The ROC curve of prognostic model for prediction of MACE. AUC of ROC was 0.732 and 95% CI was 0.642–0.822

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