Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol

Reijo Laaksonen, Kim Ekroos, Marko Sysi-Aho, Mika Hilvo, Terhi Vihervaara, Dimple Kauhanen, Matti Suoniemi, Reini Hurme, Winfried März, Hubert Scharnagl, Tatjana Stojakovic, Efthymia Vlachopoulou, Marja Liisa Lokki, Markku S. Nieminen, Roland Klingenberg, Christian M. Matter, Thorsten Hornemann, Peter Jüni, Nicolas Rodondi, Lorenz RäberStephan Windecker, Baris Gencer, Eva Ringdal Pedersen, Grethe S. Tell, Ottar Nygård, Francois Mach, Juha Sinisalo, Thomas F. Lüscher

Research output: Contribution to journalArticleScientificpeer-review

299 Citations (Scopus)

Abstract

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 ΔAUC = 0.09) in ACS and the predictive value of the Marschner score in stable CAD (NRI = 0.15 and ΔAUC = 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.

Original languageEnglish
Pages (from-to)1967-1976
Number of pages10
JournalEuropean Heart Journal
Volume37
Issue number25
DOIs
Publication statusPublished - 1 Jul 2016
MoE publication typeA1 Journal article-refereed

Keywords

  • Acute coronary syndrome
  • Biomarker
  • Ceramide
  • Coronary artery disease
  • LDL-cholesterol
  • Prognosis
  • Risk prediction

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