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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 ?AUC = 0.09) in ACS and the predictive value of the Marschner score in stable CAD (NRI = 0.15 and ?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.
SUBMITTER: Laaksonen R
PROVIDER: S-EPMC4929378 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Laaksonen Reijo R Ekroos Kim K Sysi-Aho Marko M Hilvo Mika M Vihervaara Terhi T Kauhanen Dimple D Suoniemi Matti M Hurme Reini R März Winfried W Scharnagl Hubert H Stojakovic Tatjana T Vlachopoulou Efthymia E Lokki Marja-Liisa ML Nieminen Markku S MS Klingenberg Roland R Matter Christian M CM Hornemann Thorsten T Jüni Peter P Rodondi Nicolas N Räber Lorenz L Windecker Stephan S Gencer Baris B Pedersen Eva Ringdal ER Tell Grethe S GS Nygård Ottar O Mach Francois F Sinisalo Juha J Lüscher Thomas F TF
European heart journal 20160428 25
<h4>Aims</h4>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.<h4>Methods and results</h4>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-r ...[more]