Journal
EUROPEAN HEART JOURNAL
Volume 37, Issue 25, Pages 1967-1976Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehw148
Keywords
Ceramide; Acute coronary syndrome; Coronary artery disease; Biomarker; LDL-cholesterol; Risk prediction; Prognosis
Categories
Funding
- European Union's Seventh Framework Programme RiskyCAD Project [3057392]
- Swiss National Research Foundation, Bern Switzerland [SPUM 33CM30-124112]
- Swiss Heart Foundation, Bern Switzerland
- Foundation for Cardiovascular Research-Zurich Heart House, Zurich, Switzerland
- AstraZeneca, Zug
- Eli Lilly Indianapolis, USA
- Vernier, Switzerland
- Merck Sharpe and Dohme, Glattbrugg, Switzerland
- Sanofi, Vernier, Switzerland
- St. Jude Medical, Zurich, 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]
- Zora Biosciences
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Aims 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. Methods and results 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 Delta AUC = 0.09) in ACS and the predictive value of the Marschner score in stable CAD (NRI = 0.15 and Delta AUC = 0.02). Conclusions 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.
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