Reijo Laaksonen 1 , 2 , 3 , * , Kim Ekroos 1 , Marko Sysi-Aho 1 , Mika Hilvo 1 , Terhi Vihervaara 1 , Dimple Kauhanen 1 , Matti Suoniemi 1 , Reini Hurme 1 , Winfried März 4 , 5 , Hubert Scharnagl 6 , Tatjana Stojakovic 6 , Efthymia Vlachopoulou 7 , Marja-Liisa Lokki 7 , Markku S. Nieminen 7 , 8 , Roland Klingenberg 9 , Christian M. Matter 9 , Thorsten Hornemann 10 , Peter Jüni 11 , Nicolas Rodondi 12 , 13 , Lorenz Räber 14 , Stephan Windecker 14 , Baris Gencer 15 , Eva Ringdal Pedersen 16 , Grethe S. Tell 17 , Ottar Nygård 16 , 18 , Francois Mach 15 , Juha Sinisalo 7 , 8 , Thomas F. Lüscher 10
28 April 2016
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.
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).