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

Laaksonen, Reijo; Ekroos, Kim; Sysi-Aho, Marko; Hilvo, Mika; Vihervaara, Terhi; Kauhanen, Dimple; Suoniemi, Matti; Hurme, Reini; März, Winfried; Scharnagl, Hubert; Stojakovic, Tatjana; Vlachopoulou, Efthymia; Lokki, Marja-Liisa; Nieminen, Markku S; Klingenberg, Roland; Matter, Christian M; Hornemann, Thorsten; Jüni, Peter; Rodondi, Nicolas; Räber, Lorenz; ... (2016). Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. European Heart Journal, 37(25), pp. 1967-1976. Oxford University Press 10.1093/eurheartj/ehw148

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Rodondi, Nicolas; Räber, Lorenz and Windecker, Stephan

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0195-668X

Publisher:

Oxford University Press

Language:

English

Submitter:

Judith Liniger

Date Deposited:

12 Dec 2016 15:33

Last Modified:

31 Jan 2017 13:00

Publisher DOI:

10.1093/eurheartj/ehw148

PubMed ID:

27125947

Uncontrolled Keywords:

Acute coronary syndrome Biomarker Ceramide Coronary artery disease LDL-cholesterol Prognosis Risk prediction

BORIS DOI:

10.7892/boris.89747

URI:

https://boris.unibe.ch/id/eprint/89747

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