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

作者：Reijo Laaksonen, Kim Ekroos, Marko Sysi‐Aho, Mika Hilvo, Terhi Vihervaara, Dimple Kauhanen, Matti Suoniemi, Reini Hurme, Winfried März, Hubert Scharnagl, Tatjana Stojaković, Efthymia Vlachopoulou, Marja‐Liisa Lokki, Markku S. Nieminen, Roland Klingenberg, Christian M. Matter, Thorsten Hornemann, Peter Jüni, Nicolas Rodondi, Lorenz Räber, Stephan Windecker, Bariş Gencer, Eva Ringdal Pedersen, Grethe Seppola Tell, Ottar Kjell Nygard, François Mach, Juha P. Sinisalo, Thomas Felix Lüscher · 发表于：European Heart Journal · 年份：2016 · DOI：10.1093/eurheartj/ehw148 · 被引用次数：704 · 研究领域：Sphingolipid Metabolism and Signaling、Adipokines, Inflammation, and Metabolic Diseases、Cardiovascular Health and Disease Prevention

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: D...