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

被引：503

作者：

Laaksonen, Reijo ^{[1
,2
,3
]}

Ekroos, Kim ^{[1
]}

Sysi-Aho, Marko ^{[1
]}

Hilvo, Mika ^{[1
]}

Vihervaara, Terhi ^{[1
]}

Kauhanen, Dimple ^{[1
]}

Suoniemi, Matti ^{[1
]}

Hurme, Reini ^{[1
]}

Maerz, Winfried ^{[4
,5
,6
]}

Scharnagl, Hubert ^{[7
]}

Stojakovic, Tatjana ^{[7
]}

Vlachopoulou, Efthymia ^{[8
]}

Lokki, Marja-Liisa ^{[8
]}

Nieminen, Markku S. ^{[8
,9
]}

Klingenberg, Roland ^{[10
,11
]}

Matter, Christian M. ^{[10
,11
]}

Hornemann, Thorsten ^{[12
]}

Juni, Peter ^{[13
,14
]}

Rodondi, Nicolas ^{[15
,16
]}

Raber, Lorenz ^{[17
]}

Windecker, Stephan ^{[17
]}

Gencer, Baris ^{[18
]}

Pedersen, Eva Ringdal ^{[19
]}

Tell, Grethe S. ^{[20
]}

Nygard, Ottar ^{[19
,21
]}

Mach, Francois ^{[18
]}

Sinisalo, Juha ^{[8
,9
]}

Luscher, Thomas F. ^{[12
]}

机构：

[1] Zora Biosci, Espoo, Finland

[2] Tampere Univ, Med Sch, FIN-33101 Tampere, Finland

[3] Tampere Univ Hosp, Finnish Clin Biobank Tampere, Tampere, Finland

[4] Heidelberg Univ, Med Fac Mannheim, Med Clin Nephrol Hypertensiol Rheumatol Endocrino, Heidelberg, Germany

[5] Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany

[6] Synlab Holding Deutschland GmbH, Synlab Acad, Augsburg, Germany

[7] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria

[8] Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland

[9] Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland

[10] Univ Zurich Hosp, Univ Heart Ctr, Dept Cardiol, CH-8091 Zurich, Switzerland

[11] Univ Zurich, Zurich, Switzerland

[12] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland

[13] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, AHRC, Toronto, ON, Canada

[14] Univ Toronto, Dept Med, Toronto, ON, Canada

[15] Univ Hosp Bern, Dept Gen Internal Med, CH-3010 Bern, Switzerland

[16] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland

[17] Univ Hosp Bern, Dept Cardiol, Cardiovasc Ctr, CH-3010 Bern, Switzerland

[18] Univ Hosp Geneva, Dept Cardiol, Cardiovasc Ctr, Geneva, Switzerland

[19] Univ Bergen, Dept Clin Sci, Bergen, Norway

[20] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway

[21] Haukeland Hosp, Dept Heart Dis, N-5021 Bergen, Norway

来源：

EUROPEAN HEART JOURNAL | 2016年 / 37卷 / 25期

基金：

新加坡国家研究基金会;

关键词：

Ceramide; Acute coronary syndrome; Coronary artery disease; Biomarker; LDL-cholesterol; Risk prediction; Prognosis; C-REACTIVE PROTEIN; RISK; INTERLEUKIN-6; INTERVENTION; INVOLVEMENT; IDENTIFY; PATHWAY; TARGETS;

D O I：

10.1093/eurheartj/ehw148

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1967 / 1976

页数：10

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