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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Journal ArticleDOI
Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk
Alexander M. W. Cargill Thompson,Emanuele Di Angelantonio,Nadeem Sarwar,Sebhat Erqou,Danish Saleheen,Robin P. F. Dullaart,Bernard Keavney,Zheng Ye,John Danesh +8 more
TL;DR: Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk.
Journal ArticleDOI
Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial.
Michiel L. Bots,Frank L.J. Visseren,Gregory W. Evans,Ward A. Riley,James H. Revkin,Charles H. Tegeler,Charles L. Shear,William T. Duggan,Ralph M Vicari,Diederick E. Grobbee,John J.P. Kastelein +10 more
TL;DR: Although torcetrapib substantially raised HDL cholesterol and lowered LDL cholesterol, it also increased systolic blood pressure, and did not affect the yearly rate of change in the maximum intima-media thickness of 12 carotid segments.
Journal ArticleDOI
CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction.
Jakub J. Regieli,J. Wouter Jukema,Diederick E. Grobbee,John J. P. Kastelein,Jan Albert Kuivenhoven,Aeilko H. Zwinderman,Yolanda van der Graaf,Michiel L. Bots,Pieter A. Doevendans +8 more
TL;DR: In statin-treated male CAD patients, genetic variation conferring low CETP levels is associated with increased 10-year mortality, suggesting that efficacy of statin therapy to reduce cardiovascular risk depends on CETP genotype and associated CETP plasma levels.
Journal ArticleDOI
Design of the DEFINE trial: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib
Christopher P. Cannon,Hayes M. Dansky,Michael H. Davidson,Antonio M. Gotto,Eliot A. Brinton,A. Lawrence Gould,Michael Stepanavage,Sherry Xueyu Liu,Sukrut Shah,Joseph Rubino,Patrice H. Gibbons,Anne Hermanowski-Vosatka,Bruce Binkowitz,Yale B. Mitchel,Philip J. Barter +14 more
TL;DR: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents.
Journal ArticleDOI
Apple polyphenols inhibit plasma CETP activity and reduce the ratio of non-HDL to HDL cholesterol
TL;DR: It was concluded that AP favorably improved distribution of cholesterol in lipoproteins, most likely, by its inhibition on CETP activity.
References
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Journal ArticleDOI
2D QSAR studies on a series of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one as CETP inhibitors.
TL;DR: In this article, quantitative structure-activity relationship (QSAR) models have been developed to predict the therapeutic potency of 108 derivatives of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one.
Journal ArticleDOI
High-density lipoproteins and adrenal steroidogenesis: A population-based study
TL;DR: In this population-based study, urinary glucocorticoid metabolite excretion was inversely associated with HDL-C and there was no evidence for an attenuated adrenal function in men and women with low LDL-C.
Journal ArticleDOI
HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C > A) and modified by glucocorticoid treatment
Robin P. F. Dullaart,Gerrit van den Berg,Aafke M. van der Knaap,Janneke Dijck-Brouwer,Geesje M. Dallinga-Thie,P. M. J. Zelissen,Wim J. Sluiter,André P van Beek +7 more
TL;DR: A common CETP variant-glucocorticoid treatment interaction concerning the effect of GH replacement on HDL-C is suggested, which may explain some of the reported variation in the LDL-C response to GH.
Journal ArticleDOI
CETP antagonism versus agonism in cardiovascular prevention and plaque regression
TL;DR: Re-evaluation of data on probucol clearly suggest that this drug, while lowering HDL-C because of its mechanism of action, can also reduce carotid intima-media thickness and cause negative arterial remodeling in atherosclerotic conditions.
The role of CETP and HDL metabolism in cardiac disease
TL;DR: Altered abnormalities in HDL metabolism and reverse cholesterol transport are described, i.e. the transport of cholesterol from peripheral cells back to the liver for metabolism and biliary excretion, in insulin resistance and type 2 diabetes mellitus.
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