| CETP inhibition in cardiovascular risk management: a critical appraisal. | |
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MedLine Citation:
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PMID: 17217373 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In view of the cardioprotective effect of high-density lipoproteins (HDL) and the limited effects of statin and fibrate therapy on HDL cholesterol, it is clinically relevant to test whether pharmacological treatment aimed at raising HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a new therapeutic target, because the cholesteryl ester transfer process lowers HDL cholesterol and contributes to an atherogenic lipoprotein profile, particularly when plasma triglycerides are high. Clinical evidence suggests that coronary artery calcification as well as intima media thickness is positively related to plasma cholesteryl ester transfer, and that high plasma CETP concentration is associated with increased cardiovascular risk in hypertriglyceridaemia. However, CETP could also have anti-atherogenic potential, since it provides a potentially beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In addition, CETP could also favourably stimulate peripheral cell cholesterol removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a high CETP level may confer lower cardiovascular risk in the context of low triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib elicit a marked rise in HDL cholesterol of up to 34% and 91-106%, respectively. The effectiveness of these drugs on (intermediate) clinical outcome measures is currently being tested in large-scale phase III clinical trials, with torcetrapib being only evaluated in combination therapy with atorvastatin. When and how to use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major challenge. We propose that low HDL cholesterol in the context of high triglycerides, such as found in type 2 diabetes mellitus, could become an important indication area for this new class of drugs. |
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Authors:
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R P F Dullaart; G M Dallinga-Thie; B H R Wolffenbuttel; A van Tol |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: European journal of clinical investigation Volume: 37 ISSN: 0014-2972 ISO Abbreviation: Eur. J. Clin. Invest. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-01-12 Completed Date: 2007-06-29 Revised Date: 2007-07-03 |
Medline Journal Info:
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Nlm Unique ID: 0245331 Medline TA: Eur J Clin Invest Country: England |
Other Details:
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Languages: eng Pagination: 90-8 Citation Subset: IM |
Affiliation:
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University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. r.p.f.dullaart@int.umcg.nl |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Atherosclerosis
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drug therapy* Cholesterol Ester Transfer Proteins / antagonists & inhibitors* Cholesterol, HDL / therapeutic use* Diabetes Mellitus, Type 2 / complications, drug therapy* Diabetic Angiopathies / complications, drug therapy* Humans Hypertriglyceridemia / drug therapy Risk Factors Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL |
| Comments/Corrections | |
Erratum In:
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Eur J Clin Invest. 2007 May;37(5):434 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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