Open AccessJournal Article
CETP inhibition in cardiovascular risk management: a critical appraisal (vol 37, pg 90, 2007)
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TLDR
In this paper, the effect of cholesteryl ester transfer protein (CETP) on HDL cholesterol was investigated in a large-scale phase III clinical trial, with torcetrapib being only evaluated in combination therapy with atorvastatin.Abstract:
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.read more
Citations
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How can we prevent cardiovascular disease in diabetes
TL;DR: Evidence based goals for the treatment and prevention of atherosclerosis in diabetes are given in international and national guidelines and a major possibility to reduce cardiovascular disease in diabetes is to treat patients according to guidelines.
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Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors.
Dongyin Chen,Xin Huang,Hongwen Zhou,Hanqiong Luo,Pengfei Wang,Yongzhi Chang,Xinyi He,Suiying Ni,Qingqing Shen,Guoshen Cao,Hongbin Sun,Xiaoan Wen,Jun Liu +12 more
TL;DR: Safety evaluation and pharmacokinetics studies indicated that the potential druggability for compound 20 which is a promising lead for development of a new class of CETP inhibitors for the treatment of dyslipidemia.
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Cholesteryl ester transfer protein activity and cardiovascular events in patients with chronic kidney disease stage V
Sarah Seiler,Axel Schlitt,Xian-Cheng Jiang,C. Ulrich,Stefan Blankenberg,Karl J. Lackner,Matthias Girndt,Karl Werdan,Michael Buerke,Danilo Fliser,Gunnar H. Heine +10 more
TL;DR: Neither high CETP activity nor low HDL-C was associated with CVE in CKD stage V patients, and pharmacological modification of HDL- C by CETP inhibitors seems to be of questionable value in these patients.
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Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects.
Antonio Hernández-Mijares,Juan F. Ascaso,Mariano Blasco,Ángel Brea,Ángel Díaz,Teresa Mantilla,Juan Pedro-Botet,Xavier Pintó,Jesús Millán +8 more
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Lipids and apolipoproteins in cardiovascular disease
TL;DR: There seems to be an advantage in determining the balance between good and bad cholesterol when compared to these measures by themselves when attempting to predict the development of cardiovascular disease.
References
More filters
Journal ArticleDOI
High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.
David Gordon,Jeffrey L. Probstfield,Robert J. Garrison,James D. Neaton,William P. Castelli,J. D. Knoke,David R. Jacobs,Shrikant I. Bangdiwala,H. A. Tyroler +8 more
TL;DR: A consistent inverse relation of high-density lipoprotein cholesterol levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.
Journal ArticleDOI
Molecular physiology of reverse cholesterol transport.
TL;DR: The removal of cholesterol from cells, like its delivery, appears to be specific and well regulated, and RCT can now be understood in molecular terms.
Journal ArticleDOI
Cholesteryl Ester Transfer Protein: A Novel Target for Raising HDL and Inhibiting Atherosclerosis
Philip J. Barter,H. Bryan Brewer,M. John Chapman,Charles H. Hennekens,Daniel J. Rader,Alan R. Tall +5 more
TL;DR: Small-molecule inhibitors of CETP have now been tested in human subjects and shown to increase the concentration of HDL cholesterol while decreasing that of LDL cholesterol and apoB, and test the hypothesis in randomized trials of humans that pharmacological inhibition of CETp retards the development of atherosclerosis.
Journal ArticleDOI
Diabetic dyslipidaemia: from basic research to clinical practice*
TL;DR: Recent discoveries have established the transcription factors including PPARs, SREBP-1 and LXRs as the key regulators of lipid assembly in the liver as a new target to tailor more efficient drugs to treat diabetic dyslipidaemia.
Journal ArticleDOI
Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol
Margaret E. Brousseau,Ernst J. Schaefer,Megan L. Wolfe,LeAnne T. Bloedon,Andres Digenio,Ronald W. Clark,James P. Mancuso,Daniel J. Rader +7 more
TL;DR: In subjects with low HDL cholesterol levels, CETP inhibition with torcetrapib markedly increased HDL cholesterol Levels and also decreased LDL cholesterol Levels, both when administered as monotherapy and when administered in combination with a statin.
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