Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol
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Open Access
- 28 April 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 37 (25), 1967-1976
- https://doi.org/10.1093/eurheartj/ehw148
Abstract
The aim was to study the prognostic value of plasma ceramides (Cer) as cardiovascular death (CV death) markers in three independent coronary artery disease (CAD) cohorts. Corogene study is a prospective Finnish cohort including stable CAD patients (n = 160). Multiple lipid biomarkers and C-reactive protein were measured in addition to plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1). Subsequently, the association between high-risk ceramides and CV mortality was investigated in the prospective Special Program University Medicine—Inflammation in Acute Coronary Syndromes (SPUM-ACS) cohort (n = 1637), conducted in four Swiss university hospitals. Finally, the results were validated in Bergen Coronary Angiography Cohort (BECAC), a prospective Norwegian cohort study of stable CAD patients. Ceramides, especially when used in ratios, were significantly associated with CV death in all studies, independent of other lipid markers and C-reactive protein. Adjusted odds ratios per standard deviation for the Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio were 4.49 (95% CI, 2.24–8.98), 1.64 (1.29–2.08), and 1.77 (1.41–2.23) in the Corogene, SPUM-ACS, and BECAC studies, respectively. The Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio improved the predictive value of the GRACE score (net reclassification improvement, NRI = 0.17 and ΔAUC = 0.09) in ACS and the predictive value of the Marschner score in stable CAD (NRI = 0.15 and ΔAUC = 0.02). Distinct plasma ceramide ratios are significant predictors of CV death both in patients with stable CAD and ACS, over and above currently used lipid markers. This may improve the identification of high-risk patients in need of more aggressive therapeutic interventions.Funding Information
- The European Union's Seventh Framework Programme (FP7/2007-2013)
- RiskyCAD Project (305739)
- Swiss National Research Foundation (SPUM 33CM30-124112)
- Swiss Heart Foundation
- the Foundation for Cardiovascular Research—Zürich Heart House, Zürich, Switzerland
- AstraZeneca, Zug
- Eli Lilly Indianapolis, USA
- Vernier, Medtronic, Tolochenaz
- Merck Sharpe and Dohme, Glattbrugg
- Sanofi, Vernier
- St. Jude Medical, Zürich (all Switzerland)
- Aarno Koskelo Foundation
- Helsinki University Central Hospital special government funds (EVO #TYH7215, #TKK2012005, #TYH2012209, #TYH2014312)
- Finnish Foundation for Cardiovascular Research
- Western Norway Regional Health Authority (911570)
This publication has 29 references indexed in Scilit:
- Plasma Lipid Composition and Risk of Developing Cardiovascular DiseasePLOS ONE, 2013
- ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)European Heart Journal, 2011
- Cardiovascular Risk Prediction in Patients With Stable and Unstable Coronary Heart DiseaseCirculation, 2010
- Protection of C. elegans from Anoxia by HYL-2 Ceramide SynthaseScience, 2009
- Ceramide: A common pathway for atherosclerosis?Atherosclerosis, 2008
- Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyondStatistics in Medicine, 2007
- High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trialEuropean Heart Journal, 2005
- Interleukin-6 Stimulates LDL Receptor Gene Expression via Activation of Sterol-Responsive and Sp1 Binding ElementsArteriosclerosis, Thrombosis, and Vascular Biology, 2000
- Involvement of de NovoCeramide Biosynthesis in Tumor Necrosis Factor-α/Cycloheximide-induced Cerebral Endothelial Cell DeathPublished by Elsevier BV ,1998
- Functions of Ceramide in Coordinating Cellular Responses to StressScience, 1996