A new era for quantifying hdl and cardiovascular risk?

Access through your institution Buy or subscribe High levels of low-density lipoprotein (LDL) promote atherosclerosis by delivering cholesterol in an unregulated manner to artery-wall

macrophages, a key step in atherosclerotic vascular disease. In contrast, clinical and epidemiological studies show a robust, inverse association of high-density lipoprotein (HDL) levels

with cardiovascular disease risk. HDL's cardioprotective effects are mediated in part by its ability to remove cholesterol from macrophages. Mice with genetically engineered

deficiencies in proteins involved in HDL metabolism provide compelling evidence that HDL is a key modulator of atherosclerosis in hypercholesterolemic models. These observations have

triggered intense interest in targeting HDL for therapeutic intervention. HDL can be quantified by blood concentrations of its major protein component, apoA-I, and by its content of

cholesterol. Some studies suggest that low concentrations of apoA-I associate more strongly with cardiovascular disease risk than do HDL cholesterol (HDL-C) levels. Virtually all clinical

studies have used HDL-C as a metric for quantifying HDL's cardioprotective effects. However, recent evidence has raised doubts about the hypotheses that elevating HDL-C is necessarily

therapeutic. For example, genetic variations that associate with altered HDL-C do not strongly associate with altered cardiovascular disease risk1. Also, trials of two drugs that elevate

HDL-C levels—niacin and the cholesteryl ester transfer protein (CETP) inhibitor dalceptrapib—were terminated prematurely because of an apparent lack of clinical benefit in subjects with

established cardiovascular disease1. This is a preview of subscription content, access via your institution RELEVANT ARTICLES Open Access articles citing this article. * CHOLESTEROL IS

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_Scientific Reports_ Open Access 14 August 2017 * LIPOPROTEIN HYDROPHOBIC CORE LIPIDS ARE PARTIALLY EXTRUDED TO SURFACE IN SMALLER HDL: “HERNIATED” HDL, A COMMON FEATURE IN DIABETES * Núria

Amigó * , Roger Mallol *  … Xavier Correig _Scientific Reports_ Open Access 18 January 2016 ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues

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taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Rader, D.R.

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Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Jay W. Heinecke is in the Department of Medicine, University of Washington, Seattle, Washington, USA., Jay W

Heinecke Authors * Jay W Heinecke View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jay W Heinecke. ETHICS

DECLARATIONS COMPETING INTERESTS J.W.H. receives research support from Merck, GlaxoSmithKline and Bristol-Myers Squibb. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Heinecke, J. A new era for quantifying HDL and cardiovascular risk?. _Nat Med_ 18, 1346–1347 (2012). https://doi.org/10.1038/nm.2930 Download citation * Published: 07

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