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Molecular Lipids Identify Cardiovascular Risk and Are Efficiently Lowered by Simvastatin and PCSK9 Deficiency

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 wo... Full description

Journal Title: The journal of clinical endocrinology and metabolism 2014-01, Vol.99 (1), p.E45-E52
Main Author: Tarasov, Kirill
Other Authors: Ekroos, Kim , Suoniemi, Matti , Kauhanen, Dimple , Sylvänne, Tuulia , Hurme, Reini , Gouni-Berthold, Ioanna , Berthold, Heiner K , Kleber, Marcus E , Laaksonen, Reijo , März, Winfried
Format: Electronic Article Electronic Article
Language: English
Subjects:
100
500
Publisher: United States: Endocrine Society
ID: ISSN: 0021-972X
Link: https://www.ncbi.nlm.nih.gov/pubmed/24243630
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title: Molecular Lipids Identify Cardiovascular Risk and Are Efficiently Lowered by Simvastatin and PCSK9 Deficiency
format: Article
creator:
  • Tarasov, Kirill
  • Ekroos, Kim
  • Suoniemi, Matti
  • Kauhanen, Dimple
  • Sylvänne, Tuulia
  • Hurme, Reini
  • Gouni-Berthold, Ioanna
  • Berthold, Heiner K
  • Kleber, Marcus E
  • Laaksonen, Reijo
  • März, Winfried
subjects:
  • 100
  • 500
  • Abridged Index Medicus
  • Aged
  • Azetidines - therapeutic use
  • Case-Control Studies
  • Coronary Artery Disease - blood
  • Coronary Artery Disease - drug therapy
  • Coronary Artery Disease - epidemiology
  • Ezetimibe
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Hot Topics in Translational Endocrinology
  • Humans
  • Hypolipidemic Agents - therapeutic use
  • Lipids - blood
  • Macromolecular Substances - blood
  • Male
  • Middle Aged
  • Proprotein Convertase 9
  • Proprotein Convertases - deficiency
  • Proprotein Convertases - genetics
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Serine Endopeptidases - deficiency
  • Serine Endopeptidases - genetics
  • Simvastatin - therapeutic use
ispartof: The journal of clinical endocrinology and metabolism, 2014-01, Vol.99 (1), p.E45-E52
description: 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.
language: eng
source:
identifier: ISSN: 0021-972X
fulltext: no_fulltext
issn:
  • 0021-972X
  • 1945-7197
url: Link


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titleMolecular Lipids Identify Cardiovascular Risk and Are Efficiently Lowered by Simvastatin and PCSK9 Deficiency
creatorTarasov, Kirill ; Ekroos, Kim ; Suoniemi, Matti ; Kauhanen, Dimple ; Sylvänne, Tuulia ; Hurme, Reini ; Gouni-Berthold, Ioanna ; Berthold, Heiner K ; Kleber, Marcus E ; Laaksonen, Reijo ; März, Winfried
creatorcontribTarasov, Kirill ; Ekroos, Kim ; Suoniemi, Matti ; Kauhanen, Dimple ; Sylvänne, Tuulia ; Hurme, Reini ; Gouni-Berthold, Ioanna ; Berthold, Heiner K ; Kleber, Marcus E ; Laaksonen, Reijo ; März, Winfried
descriptionContext: 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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descriptionContext: 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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notesThis work was supported by European Union (integrated project Atheroremo, Grant 201668) and by Tekes, Finnish Funding Agency for Technology, and Innovation.
abstractContext: 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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