Universität zu Köln

Tarasov, Kirill, Ekroos, Kim, Suoniemi, Matti, Kauhanen, Dimple, Sylvanne, Tuulia, Hurme, Reini, Gouni-Berthold, Ioanna, Berthold, Heiner K., Kleber, Marcus E., Laaksonen, Reijo and Maerz, Winfried (2014). Molecular Lipids Identify Cardiovascular Risk and Are Efficiently Lowered by Simvastatin and PCSK9 Deficiency. J. Clin. Endocrinol. Metab., 99 (1). S. E45 - 8. WASHINGTON: ENDOCRINE SOC. ISSN 1945-7197

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Abstract

Context: Coronary artery disease (CAD) is among the leading causes of mortality and morbidity worldwide. Traditional risk markers explain only a proportion of total cardiovascular risk. Thus, development and improvement of early diagnostic strategies and targeted initiation of preventive measures would be of great benefit. Objective: We aimed to identify molecular lipids that are associated with fatal outcome of CAD patients. Furthermore, the effect of different lipid-lowering drugs on novel risk lipids was evaluated. Methods: Serum samples of 445 CAD subjects participating in a long-term follow-up of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study were analyzed. In addition, samples obtained from a separate randomized parallel three-group study of subjects treated with simvastatin (n = 24), ezetimibe (n = 24), or their combination (n = 24) were studied. Furthermore, samples from the LURIC participants with a loss-of-function mutation (R46L) in the PCSK9 gene (n = 19) were analyzed and compared with major allele carriers (n = 868). Results: Distinct ceramide species were significantly associated with the fatal outcome of CAD patients. Simvastatin lowered plasma ceramides broadly by about 25%, but no changes in ceramides were observed in the ezetimibe group. PCSK9 deficiency was significantly associated (-13%) with lowered low-density lipoprotein cholesterol accompanied by a significant 20% reduction in CAD outcome risk-related ceramides. Conclusions: These data suggest that distinct ceramides associate significantly with CAD outcome independently of traditional risk factors and that the mechanism of lipid lowering is important.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tarasov, Kirill UNSPECIFIED UNSPECIFIED UNSPECIFIED Ekroos, Kim UNSPECIFIED UNSPECIFIED UNSPECIFIED Suoniemi, Matti UNSPECIFIED UNSPECIFIED UNSPECIFIED Kauhanen, Dimple UNSPECIFIED UNSPECIFIED UNSPECIFIED Sylvanne, Tuulia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hurme, Reini UNSPECIFIED UNSPECIFIED UNSPECIFIED Gouni-Berthold, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Berthold, Heiner K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleber, Marcus E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Laaksonen, Reijo UNSPECIFIED UNSPECIFIED UNSPECIFIED Maerz, Winfried UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-452389
DOI:	10.1210/jc.2013-2559
Journal or Publication Title:	J. Clin. Endocrinol. Metab.
Volume:	99
Number:	1
Page Range:	S. E45 - 8
Date:	2014
Publisher:	ENDOCRINE SOC
Place of Publication:	WASHINGTON
ISSN:	1945-7197
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIGH-THROUGHPUT; PLASMA; ATHEROSCLEROSIS; DISEASE; PHOSPHOLIPIDS; LIPOPROTEINS; CHOLESTEROL; LIPIDOMICS; REDUCTION; PLAQUE Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45238