Molecular Lipids Identify Cardiovascular Risk and Are Efficiently Lowered by Simvastatin and PCSK9 Deficiency
K Tarasov, K Ekroos, M Suoniemi… - The Journal of …, 2014 - academic.oup.com
K Tarasov, K Ekroos, M Suoniemi, D Kauhanen, T Sylvänne, R Hurme, I Gouni-Berthold…
The Journal of Clinical Endocrinology & Metabolism, 2014•academic.oup.comContext: 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 …
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 …
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.
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