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Associations between specific plasma ceramides and severity of coronary-artery stenosis assessed by coronary angiography - 22/04/20

Doi : 10.1016/j.diabet.2019.07.006 
A. Mantovani a, S. Bonapace b, G. Lunardi c, G. Canali b, C. Dugo b, G. Vinco a, d, S. Calabria e, E. Barbieri b, R. Laaksonen f, g, F. Bonnet h, C.D. Byrne i, j, G. Targher a,
a Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy 
b Division of Cardiology, “IRCCS Sacro Cuore - Don Calabria” Hospital, Negrar (VR), Italy 
c Division of Medical Oncology, “IRCCS Sacro Cuore - Don Calabria” Hospital, Negrar (VR), Italy 
d Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy 
e Division of Internal Medicine, IRCCS Sacro Cuore–Don Calabria Hospital, Negrar (VR), Italy 
f Finnish Cardiovascular Research Center Tampere, University of Tampere, Faculty of Medicine and Life Sciences and Tampere University Hospital, Finland 
g Zora Biosciences Oy, Espoo, Finland 
h Department of Endocrinology, INSERM U1018, Groupe Hospitalier Paris Saint-Joseph, Paris, France 
i Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK 
j Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK 

Corresponding author at: Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata, Piazzale Stefani, 1, 37126 Verona, Italy.Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata, Piazzale Stefani, 1Verona37126Italy

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Abstract

Aim

Recent prospective studies have identified distinct plasma ceramides as strong predictors of major adverse cardiovascular events in patients with established or suspected coronary artery disease (CAD). Currently, it is uncertain whether higher levels of distinct plasma ceramides are associated with greater angiographic severity of coronary-artery stenoses in this patient population.

Methods

We measured six previously identified high-risk plasma 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)] in 167 consecutive patients with established or suspected CAD, who underwent urgent or elective coronary angiography.

Results

Approximately 77% of patients had a significant stenosis (≥50%) in one or more of the main coronary arteries, the majority of whom (∼60%) had a significant stenosis in the left anterior descending (LAD) artery. Of the six measured plasma ceramides, higher levels of plasma Cer(d18:1/20:0) (adjusted-odds ratio 1.39, 95%CI 1.0–1.99), Cer(d18:1/22:0) (adjusted-odds ratio 1.57, 95%CI 1.08–2.29) and Cer(d18:1/24:0) (adjusted-odds ratio 1.59, 95%CI 1.08–2.32) were significantly associated with the presence of LAD stenosis50%, after adjustment for age, sex, smoking, pre-existing CAD, hypertension, diabetes, dyslipidaemia, lipid-lowering therapy, estimated glomerular filtration rate and plasma C-reactive protein levels. Almost identical results were found even after excluding patients (n=15) with acute ST-elevation myocardial infarction. Similar results were also found when patients were categorized according to the Gensini severity score.

Conclusion

Our cross-sectional study shows for the first time that higher levels of specific plasma ceramides are independently associated with a greater severity of coronary-artery stenoses in the LAD artery in patients who had suspected or established CAD.

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Keywords : Ceramides, Coronary angiography, Coronary artery disease, Risk factors

Abbreviations : BMI, Cer, CAD, CKD, CRP, e-GFR, FDR, LAD, LCX, MDRD, RCA


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