Associations between specific plasma ceramides and severity of coronary-artery stenosis assessed by coronary angiography

Mantovani, Alessandro; Bonapace, Stefano; Lunardi, Gianluigi; Canali, G; Dugo, Clementina; Vinco, Giulia; Calabria, Stefano; Barbieri, Enrico; Laaksonen, Reijo; Bonnet, Fabrice; Byrne, Christopher D.; Targher, Giovanni

doi:10.1016/j.diabet.2019.07.006

Cited by 34 publications

(28 citation statements)

References 26 publications

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“…For the first time that the association between high level of Cer (d18:0/24:1)/ Cer (d18:0/24:0) ratio and more severe coronary artery stenosis is reported, and there was no association between any specific ceramide and severity of coronary artery stenosis found in the present study. Recently, Mantovani and colleagues [29] reported that a higher level of plasma Cer (d18:1/24:0), but not Cer (d18:0/24:1), was associated with a greater severity of LAD stenosis after adjustment for cardiovascular risk factors. However, Cer (d18:0/24:1)/Cer (d18:0/24:0) ratio was not investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

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

Xie

Wang

et al. 2020

Lipids Health Dis

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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.

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Section: Discussionmentioning

confidence: 99%

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

Xie

Wang

et al. 2020

Lipids Health Dis

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“…Saturated fat induces more pronounced increases in intrahepatic triglyceride content and insulin resistance compared to unsaturated fat and simple sugars [51]. Plasma lipids might also be disease relevant as shown for certain ceramides which concentrations were independently associated with greater severity of coronary artery stenosis in the left anterior descending artery [52]. Mitochondrial dysfunction and endoplasmic reticulum stress activation are also key factors contributing to NAFLD and insulin resistance [53].…”

Section: Multiple Sources Of Cytokines Drive Liver Inflammation and Ementioning

confidence: 99%

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Targher

Byrne

Tilg

2020

Gut

515

365

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Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to a third of the world’s adult population. Several cohort studies have consistently documented that NAFLD (especially in its more advanced forms) is associated with a higher risk of all-cause mortality and that the leading causes of death among patients with NAFLD are cardiovascular diseases (CVDs), followed by extrahepatic malignancies and liver-related complications. A growing body of evidence also indicates that NAFLD is strongly associated with an increased risk of major CVD events and other cardiac complications (ie, cardiomyopathy, cardiac valvular calcification and cardiac arrhythmias), independently of traditional cardiovascular risk factors. This narrative review provides an overview of the literature on: (1) the evidence for an association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications, (2) the putative pathophysiological mechanisms linking NAFLD to CVD and other cardiac complications and (3) the current pharmacological treatments for NAFLD that might also benefit or adversely affect risk of CVD.

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“…1,3,4 Large prospective studies have recently identified plasma ceramides with long and very-long chains [mostly increased plasma levels of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer (d18:1/24:1) and their ratios with Cer(d18:1/24:0)] as significant predictors of cardiovascular morbidity and mortality both in the general population 5 and in patients with established coronary artery disease (CAD) or acute coronary syndrome, independent of traditional cardiovascular risk factors. [6][7][8][9] Additionally, higher levels of these plasma ceramides have been strongly associated with greater angiographic severity of coronary stenoses in patients with CAD, 10 as well as with lower post-stress myocardial wall perfusion in patients with established, or suspected, CAD undergoing stress myocardial perfusion scintigraphy. 11 That said, in this hypothesis-generating study, we have supposed that there is a significant association between higher plasma levels of specific ceramides (that have been previously associated with higher risk of adverse cardiovascular outcomes in patients with CAD) and the risk of cardiovascular mortality also in patients with chronic heart failure (HF), that is, a progressive, complex clinical syndrome characterized by high rates of cardiovascular morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

“…Large prospective studies have recently identified plasma ceramides with long and very‐long chains [mostly increased plasma levels of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and their ratios with Cer(d18:1/24:0)] as significant predictors of cardiovascular morbidity and mortality both in the general population 5 and in patients with established coronary artery disease (CAD) or acute coronary syndrome, independent of traditional cardiovascular risk factors 6–9 . Additionally, higher levels of these plasma ceramides have been strongly associated with greater angiographic severity of coronary stenoses in patients with CAD, 10 as well as with lower post‐stress myocardial wall perfusion in patients with established, or suspected, CAD undergoing stress myocardial perfusion scintigraphy 11 …”

Section: Introductionmentioning

confidence: 99%

Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial

et al. 2020

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Aims Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention. Methods and results In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure (GISSI-HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow-up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high-risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer (d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin-3 levels, and, especially, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P-threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23). Conclusions Higher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT-proBNP concentrations.

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Associations between specific plasma ceramides and severity of coronary-artery stenosis assessed by coronary angiography

Cited by 34 publications

References 26 publications

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

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

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial

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