title: Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol.
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.
authors.affiliation: Zora Biosciences, Espoo, Finland Medical School, Tampere University, Tampere, Finland Finnish Clinical Biobank Tampere, University Hospital of Tampere, Tampere, Finland reijo.laaksonen@zora.fi.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Kim
authors.initials: K
authors.lastname: Ekroos
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Sysi-Aho
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Hilvo
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Vihervaara
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Dimple
authors.initials: D
authors.lastname: Kauhanen
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Suoniemi
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Reini
authors.initials: R
authors.lastname: Hurme
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany synlab Academy, synlab Holding Deutschland GmbH, Mannheim and Augsburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Efthymia
authors.initials: E
authors.lastname: Vlachopoulou
authors.affiliation: Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
authors.affiliation: Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
authors.affiliation: Institute of Clinical Chemistry, University Hospital, Zürich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hornemann
authors.affiliation: Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: Department of General Internal Medicine, University Hospital Bern, Bern, Switzerland Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.affiliation: Cardiovascular Center, Department of Cardiology, University Hospital Bern, Bern, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Räber
authors.affiliation: Cardiovascular Center, Department of Cardiology, University Hospital Bern, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Cardiovascular Center, Department of Cardiology, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Baris
authors.initials: B
authors.lastname: Gencer
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Eva Ringdal
authors.initials: ER
authors.lastname: Pedersen
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.affiliation: Cardiovascular Center, Department of Cardiology, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Francois
authors.initials: F
authors.lastname: Mach
authors.affiliation: Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
authors.affiliation: Institute of Clinical Chemistry, University Hospital, Zürich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D054058:Acute Coronary Syndrome; D015415:Biomarkers; D002518:Ceramides; D008078:Cholesterol, LDL; D003324:Coronary Artery Disease; D006801:Humans; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002518:Ceramides; D008078:Cholesterol, LDL
keywords: Acute coronary syndrome; Biomarker; Ceramide; Coronary artery disease; LDL-cholesterol; Prognosis; Risk prediction