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Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk

Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effe...

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Autores principales: Yanai, Hidekatsu, Adachi, Hiroki, Hakoshima, Mariko, Katsuyama, Hisayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657259/
https://www.ncbi.nlm.nih.gov/pubmed/36362288
http://dx.doi.org/10.3390/ijms232113499
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author Yanai, Hidekatsu
Adachi, Hiroki
Hakoshima, Mariko
Katsuyama, Hisayuki
author_facet Yanai, Hidekatsu
Adachi, Hiroki
Hakoshima, Mariko
Katsuyama, Hisayuki
author_sort Yanai, Hidekatsu
collection PubMed
description Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effect of statins vs. a placebo on CVD development, 56–79% of patients had residual CVD risk after the trials. In three RCTs that investigated the effect of a high dose vs. a usual dose of statins on CVD development, 78–87% of patients in the high-dose statin arms still had residual CVD risk. The risk of CVD development remains even when statins are used to strongly reduce LDL-C, and this type of risk is now regarded as statin residual CVD risk. Our study shows that elevated triglyceride (TG) levels, reduced high-density lipoprotein cholesterol (HDL-C), and the existence of obesity/insulin resistance and diabetes may be important metabolic factors that determine statin residual CVD risk. Here, we discuss atherogenic lipoproteins that were not investigated in such RCTs, such as lipoprotein (a) (Lp(a)), remnant lipoproteins, malondialdehyde-modified LDL (MDA-LDL), and small-dense LDL (Sd-LDL). Lp(a) is under strong genetic control by apolipoprotein (a), which is an LPA gene locus. Variations in the LPA gene account for 91% of the variability in the plasma concentration of Lp(a). A meta-analysis showed that genetic variations at the LPA locus are associated with CVD events during statin therapy, independent of the extent of LDL lowering, providing support for exploring strategies targeting circulating concentrations of Lp(a) to reduce CVD events in patients receiving statins. Remnant lipoproteins and small-dense LDL are highly associated with high TG levels, low HDL-C, and obesity/insulin resistance. MDA-LDL is a representative form of oxidized LDL and plays important roles in the formation and development of the primary lesions of atherosclerosis. MDA-LDL levels were higher in CVD patients and diabetic patients than in the control subjects. Furthermore, we demonstrated the atherogenic properties of such lipoproteins and their association with CVD as well as therapeutic approaches.
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spelling pubmed-96572592022-11-15 Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk Yanai, Hidekatsu Adachi, Hiroki Hakoshima, Mariko Katsuyama, Hisayuki Int J Mol Sci Review Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effect of statins vs. a placebo on CVD development, 56–79% of patients had residual CVD risk after the trials. In three RCTs that investigated the effect of a high dose vs. a usual dose of statins on CVD development, 78–87% of patients in the high-dose statin arms still had residual CVD risk. The risk of CVD development remains even when statins are used to strongly reduce LDL-C, and this type of risk is now regarded as statin residual CVD risk. Our study shows that elevated triglyceride (TG) levels, reduced high-density lipoprotein cholesterol (HDL-C), and the existence of obesity/insulin resistance and diabetes may be important metabolic factors that determine statin residual CVD risk. Here, we discuss atherogenic lipoproteins that were not investigated in such RCTs, such as lipoprotein (a) (Lp(a)), remnant lipoproteins, malondialdehyde-modified LDL (MDA-LDL), and small-dense LDL (Sd-LDL). Lp(a) is under strong genetic control by apolipoprotein (a), which is an LPA gene locus. Variations in the LPA gene account for 91% of the variability in the plasma concentration of Lp(a). A meta-analysis showed that genetic variations at the LPA locus are associated with CVD events during statin therapy, independent of the extent of LDL lowering, providing support for exploring strategies targeting circulating concentrations of Lp(a) to reduce CVD events in patients receiving statins. Remnant lipoproteins and small-dense LDL are highly associated with high TG levels, low HDL-C, and obesity/insulin resistance. MDA-LDL is a representative form of oxidized LDL and plays important roles in the formation and development of the primary lesions of atherosclerosis. MDA-LDL levels were higher in CVD patients and diabetic patients than in the control subjects. Furthermore, we demonstrated the atherogenic properties of such lipoproteins and their association with CVD as well as therapeutic approaches. MDPI 2022-11-04 /pmc/articles/PMC9657259/ /pubmed/36362288 http://dx.doi.org/10.3390/ijms232113499 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
Yanai, Hidekatsu
Adachi, Hiroki
Hakoshima, Mariko
Katsuyama, Hisayuki
Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk
title Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk
title_full Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk
title_fullStr Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk
title_full_unstemmed Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk
title_short Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk
title_sort atherogenic lipoproteins for the statin residual cardiovascular disease risk
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657259/
https://www.ncbi.nlm.nih.gov/pubmed/36362288
http://dx.doi.org/10.3390/ijms232113499
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