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Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels

Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C)...

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Autores principales: Nelson, Adam J., Sniderman, Allan D., Ditmarsch, Marc, Dicklin, Mary R., Nicholls, Stephen J., Davidson, Michael H., Kastelein, John J. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409323/
https://www.ncbi.nlm.nih.gov/pubmed/36012684
http://dx.doi.org/10.3390/ijms23169417
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author Nelson, Adam J.
Sniderman, Allan D.
Ditmarsch, Marc
Dicklin, Mary R.
Nicholls, Stephen J.
Davidson, Michael H.
Kastelein, John J. P.
author_facet Nelson, Adam J.
Sniderman, Allan D.
Ditmarsch, Marc
Dicklin, Mary R.
Nicholls, Stephen J.
Davidson, Michael H.
Kastelein, John J. P.
author_sort Nelson, Adam J.
collection PubMed
description Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.
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spelling pubmed-94093232022-08-26 Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels Nelson, Adam J. Sniderman, Allan D. Ditmarsch, Marc Dicklin, Mary R. Nicholls, Stephen J. Davidson, Michael H. Kastelein, John J. P. Int J Mol Sci Review Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction. MDPI 2022-08-20 /pmc/articles/PMC9409323/ /pubmed/36012684 http://dx.doi.org/10.3390/ijms23169417 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Nelson, Adam J.
Sniderman, Allan D.
Ditmarsch, Marc
Dicklin, Mary R.
Nicholls, Stephen J.
Davidson, Michael H.
Kastelein, John J. P.
Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
title Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
title_full Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
title_fullStr Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
title_full_unstemmed Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
title_short Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels
title_sort cholesteryl ester transfer protein inhibition reduces major adverse cardiovascular events by lowering apolipoprotein b levels
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409323/
https://www.ncbi.nlm.nih.gov/pubmed/36012684
http://dx.doi.org/10.3390/ijms23169417
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