TY - JOUR
T1 - Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol
AU - Laaksonen, Reijo
AU - Ekroos, Kim
AU - Sysi-Aho, Marko
AU - Hilvo, Mika
AU - Vihervaara, Terhi
AU - Kauhanen, Dimple
AU - Suoniemi, Matti
AU - Hurme, Reini
AU - März, Winfried
AU - Scharnagl, Hubert
AU - Stojakovic, Tatjana
AU - Vlachopoulou, Efthymia
AU - Lokki, Marja Liisa
AU - Nieminen, Markku S.
AU - Klingenberg, Roland
AU - Matter, Christian M.
AU - Hornemann, Thorsten
AU - Jüni, Peter
AU - Rodondi, Nicolas
AU - Räber, Lorenz
AU - Windecker, Stephan
AU - Gencer, Baris
AU - Pedersen, Eva Ringdal
AU - Tell, Grethe S.
AU - Nygård, Ottar
AU - Mach, Francois
AU - Sinisalo, Juha
AU - Lüscher, Thomas F.
N1 - Publisher Copyright:
© 2016 The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Acute coronary syndrome
KW - Biomarker
KW - Ceramide
KW - Coronary artery disease
KW - LDL-cholesterol
KW - Prognosis
KW - Risk prediction
UR - http://www.scopus.com/inward/record.url?scp=84977519129&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehw148
DO - 10.1093/eurheartj/ehw148
M3 - Article
C2 - 27125947
AN - SCOPUS:84977519129
VL - 37
SP - 1967
EP - 1976
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 25
ER -