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. 2016 Jul 1;37(25):1967-76.
doi: 10.1093/eurheartj/ehw148. Epub 2016 Apr 28.

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

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

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

Reijo Laaksonen et al. Eur Heart J. .

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 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.

Keywords: Acute coronary syndrome; Biomarker; Ceramide; Coronary artery disease; LDL-cholesterol; Prognosis; Risk prediction.

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Figures

Figure 1
Figure 1
Cardiovascular death odds ratios for per standard deviation and 4th quartile for different lipid markers and ceramides in Corogene study. Adjustment is made for total cholesterol, triacylglycerols, LDL-C, HDL-C, and C-reactive protein.
See this image and copyright information in PMC

References

    1. Morrow DA. Cardiovascular risk prediction in patients with stable and unstable coronary heart disease. Circulation 2010;121:2681–2691. - PubMed
    1. Hamm CW, Bassand J-P, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevatio. Eur Heart J 2011;32:2999–3054. - PubMed
    1. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot J-S, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabaté M, Senior R, Taggart DP, van der Wall EE, Vrints CJM, Zamorano JL, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Valgimigli M, Claeys MJ, Donner-Banzhoff N, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Husted S, James SK, Kervinen K, Kristensen SD, Pietro MA, Pries AR, Romeo F, Rydén L, Simoons ML, Steg PG, Timmis A, Yildirir A. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003. - PubMed
    1. Tarasov K, Ekroos K, Suoniemi M, Kauhanen D, Sylvänne T, Hurme R, Gouni-Berthold I, Berthold HK, Kleber ME, Laaksonen R, März W. Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency. J Clin Endocrinol Metab 2014;99:E45–E52. - PMC - PubMed
    1. Meikle PJ, Wong G, Tsorotes D, Barlow CK, Weir JM, Christopher MJ, MacIntosh GL, Goudey B, Stern L, Kowalczyk A, Haviv I, White AJ, Dart AM, Duffy SJ, Jennings GL, Kingwell BA, Weir M. Plasma lipidomic analysis of stable and unstable coronary artery disease. Arterioscler Thromb Vasc Biol 2011;31:2723–2732. - PubMed