CETP and memory decline: A link?

A preliminary report suggests that a polymorphism in the CETP gene might be associated with slower memory decline, and a lower incidence of dementia. Professor Philip Barter, HDL Forum Editor, from the Heart Research Institute, Sydney, Australia discusses these intriguing findings.
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CETP and mortality: Expert Analysis

Data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study suggest that low CETP levels are associated with increased mortality, contrary to extensive published evidence. Professor Philip Barter, HDL Forum Editor, Heart Research Institute, Sydney Australia provides expert analysis of the study here.
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Latest trial confirms efficacy/safety profile of CETP inhibition with dalcetrapib

The first mid-term follow-up data on dalcetrapib show a favourable efficacy/safety profile, supporting ongoing clinical development for this potential HDL cholesterol raising strategy. The data were reported and reviewed in the European Heart Journal, and are discussed by HDL Forum Editor Professor Philip Barter, Heart Research Institute, Sydney, Australia.
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CETP inhibition unlikely to be responsible for hypertensive effects of torcetrapib

A large-scale collaborative analysis of data from torcetrapib trials and genetic studies adds to evidence suggesting that the hypertensive effects observed with torcetrapib are unlikely to be related to cholesteryl ester transfer protein (CETP) inhibition. These findings, reported in Circulation, will help to reassure the clinical community that chemically dissimilar CETP inhibitors currently in development are unlikely to share this adverse effect.
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Framingham CETP analysis: Response from HDL Forum

Prospective cohort analysis from the Framingham Heart Study suggests that lowering cholesteryl ester transfer protein (CETP) activity increases cardiovascular risk. This conclusion runs contrary to an extensive body of published evidence showing an increase in coronary risk with increasing CETP activity.HDL Forum Editors Professor Kerry-Anne Rye and Professor Philip Barter, Heart Research Institute, Sydney Australia and Professor John Chapman
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DEFINE trial: efficacy and tolerability of anacetrapib

Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is an ongoing international study in statin-treated patients with coronary heart disease (CHD) or CHD risk equivalents. In total, 1623 patients have been randomized to treatment in 153 centres in 20 countries. The study is planned to report in late 2010. The study and its potential implications were reviewed by HDL Forum Editor Professor Philip Barter.
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CETP inhibition modulates HDL2 and HDL3 activity in reverse cholesterol transport in mixed dyslipidemia

In patients with mixed dyslipidemia (Type IIb dyslipidemia), typical of type 2 diabetes and metabolic syndrome, HDL particles exhibit structural and compositional changes and have defective function. In part, this is thought to be due to be due to changes within the reverse cholesterol transport pathway resulting from increasing activity of cholesteryl ester transfer protein (CETP).
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Therapeutic potential for CETP inhibition? Further data from the torcetrapib trials

Therapeutic potential for CETP inhibition? Further data from the torcetrapib trials

Further data from the RADIANCE and ILLUSTRATE trials with the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib indicate that aldosterone off-target toxicity contributes to adverse outcomes. These data add to analyses from the ILLUMINATE trial, previously discussed on CETPi.
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New data from ILLUMINATE

According to HDL Forum Editor and author Professor Philip Barter, exploratory post hoc analyses of the ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact on Atherosclerotic Events) trial failed to identify a contributing role of lipid effects and/or off-target pharmacology of torcetrapib and its clinical harm. The findings were reported at the American Heart Association Scientific Sessions 2008.
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Dalcetrapib, a CETP inhibitor, does not increase aldosterone production

A report from researchers at the University Hospital Geneva, Switzerland showed that the effects of the cholesteryl ester transfer protein (CETP) inhibitors on aldosterone production differ. Unlike torcetrapib, dalcetrapib is not a steroidogenic agent. Neither in vitro production of aldosterone or expression of the aldosterone synthase gene CYP11B2 was increased with dalcetrapib. The results were reported at the American Heart Association Annual Scientific Sessions, New Orleans 2008.
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CETP INHIBITION: WHERE NOW?

A position statement by Philip Barter and Kerry-Anne Rye The Heart Research Institute, Sydney, Australia
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New safety data on CETP inhibitor RO4607381/JJT-705

Data presented at the American College of Cardiology Scientific Sessions, Chicago, March 20-April show that the new cholesteryl ester transfer protein (CETP) inhibitor RO4607381/JJT-705 is well tolerated with no indication of any treatment-related increase in blood pressure. As well, experimental studies in an animal model show that RO4607381/JTT-705 had no impact on blood pressure or rennin-angiotensin system gene expression.
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New CETP inhibitor shows promise

The second study was designed to investigate the effects of anacetrapib on 24-hour ambulatory blood pressure. Clinical trials with torcetrapib, another CETP inhibitor, had shown significant increases in blood pressure associated with treatment.
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New data from ILLUMINATE: outcome trial with torcetrapib

New data from the ILLUMINATE trial, published on-line in the New England Journal of Medicine, November 5 do not disprove the hypothesis that CETP inhibition is cardioprotective. Further testing with a different CETP inhibitor that does not share off-target effects of torcetrapib is needed.
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OTHER AHA 2007 reports

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Promising data on new CETP inhibitor

MK-0859, a new cholesteryl ester transfer protein (CETP) inhibitor, produces effective dose-dependent lipid-lowering and is well tolerated.
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Disappointing results with major studies with torcetrapib

Results from ILLUSTRATE and RADIANCE failed to demonstrate any benefit on progression of atherosclerosis with torcetrapib administered in combination with atorvastatin, despite substantial increases in HDL cholesterol.
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Results of RADIANCE 2 trial

July 2007 - Administration of torcetrapib did not influence atherosclerosis progression despite substantially raising HDL cholesterol levels, according to the results of the RADIANCE 2 study, published in the Lancet.
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