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Implications of torcetrapib failure for the future of HDL therapy: is HDL-cholesterol the right target?


von Eckardstein, Arnold (2010). Implications of torcetrapib failure for the future of HDL therapy: is HDL-cholesterol the right target? Expert Review of Cardiovascular Therapy, 8(3):345-358.

Abstract

Owing to many potentially anti-atherogenic functions and the inverse correlation of high-density lipoprotein (HDL)-cholesterol (C) plasma levels with cardiovascular risk, HDLs have evolved as an attractive target for the prevention and therapy of coronary heart disease. Previously, the failure of torcetrapib, the frequent confounding of low HDL-C with other pro-atherogenic conditions, as well as inconsistent data from patients and animal models with genetic HDL dyslipidemias, left in doubt the suitability of HDL-C as a target for anti-atherogenic therapy. However, HDL-C is an integrative but nonfunctional measure of particle size and number. Therefore, biomarkers reflecting the functionality of HDL particles are needed to assess and monitor the cardiovascular risk exerted by disturbances and treatments of HDL metabolism, respectively. Moreover, the discovery of novel therapeutics that improve HDL metabolism, mimic HDL function, or cure the regulatory network underlying dyslipidemias and dysfunctions of HDL should be a major aim of atherosclerosis research.

Abstract

Owing to many potentially anti-atherogenic functions and the inverse correlation of high-density lipoprotein (HDL)-cholesterol (C) plasma levels with cardiovascular risk, HDLs have evolved as an attractive target for the prevention and therapy of coronary heart disease. Previously, the failure of torcetrapib, the frequent confounding of low HDL-C with other pro-atherogenic conditions, as well as inconsistent data from patients and animal models with genetic HDL dyslipidemias, left in doubt the suitability of HDL-C as a target for anti-atherogenic therapy. However, HDL-C is an integrative but nonfunctional measure of particle size and number. Therefore, biomarkers reflecting the functionality of HDL particles are needed to assess and monitor the cardiovascular risk exerted by disturbances and treatments of HDL metabolism, respectively. Moreover, the discovery of novel therapeutics that improve HDL metabolism, mimic HDL function, or cure the regulatory network underlying dyslipidemias and dysfunctions of HDL should be a major aim of atherosclerosis research.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
540 Chemistry
Language:English
Date:2010
Deposited On:16 Feb 2011 14:36
Last Modified:07 Dec 2017 07:26
Publisher:Informa Healthcare
ISSN:1477-9072
Publisher DOI:https://doi.org/10.1586/erc.10.6
PubMed ID:20222814

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