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Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia
For almost a century, familial hypercholesterolemia (FH) has been considered a serious disease, causing atherosclerosis, cardiovascular disease, and ischemic stroke. Closely related to this is the widespread acceptance that its cause is greatly increased low-density-lipoprotein cholesterol (LDL-C)....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409002/ https://www.ncbi.nlm.nih.gov/pubmed/36012410 http://dx.doi.org/10.3390/ijms23169146 |
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author | Ravnskov, Uffe de Lorgeril, Michel Kendrick, Malcolm Diamond, David M. |
author_facet | Ravnskov, Uffe de Lorgeril, Michel Kendrick, Malcolm Diamond, David M. |
author_sort | Ravnskov, Uffe |
collection | PubMed |
description | For almost a century, familial hypercholesterolemia (FH) has been considered a serious disease, causing atherosclerosis, cardiovascular disease, and ischemic stroke. Closely related to this is the widespread acceptance that its cause is greatly increased low-density-lipoprotein cholesterol (LDL-C). However, numerous observations and experiments in this field are in conflict with Bradford Hill’s criteria for causality. For instance, those with FH demonstrate no association between LDL-C and the degree of atherosclerosis; coronary artery calcium (CAC) shows no or an inverse association with LDL-C, and on average, the life span of those with FH is about the same as the surrounding population. Furthermore, no controlled, randomized cholesterol-lowering trial restricted to those with FH has demonstrated a positive outcome. On the other hand, a number of studies suggest that increased thrombogenic factors—either procoagulant or those that lead to high platelet reactivity—may be the primary risk factors in FH. Those individuals who die prematurely have either higher lipoprotein (a) (Lp(a)), higher factor VIII and/or higher fibrinogen compared with those with a normal lifespan, whereas their LDL-C does not differ. Conclusions: Many observational and experimental studies have demonstrated that high LDL-C cannot be the cause of premature cardiovascular mortality among people with FH. The number who die early is also much smaller than expected. Apparently, some individuals with FH may have inherited other, more important risk factors than a high LDL-C. In accordance with this, our review has shown that increased coagulation factors are the commonest cause, but there may be other ones as well. |
format | Online Article Text |
id | pubmed-9409002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94090022022-08-26 Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia Ravnskov, Uffe de Lorgeril, Michel Kendrick, Malcolm Diamond, David M. Int J Mol Sci Review For almost a century, familial hypercholesterolemia (FH) has been considered a serious disease, causing atherosclerosis, cardiovascular disease, and ischemic stroke. Closely related to this is the widespread acceptance that its cause is greatly increased low-density-lipoprotein cholesterol (LDL-C). However, numerous observations and experiments in this field are in conflict with Bradford Hill’s criteria for causality. For instance, those with FH demonstrate no association between LDL-C and the degree of atherosclerosis; coronary artery calcium (CAC) shows no or an inverse association with LDL-C, and on average, the life span of those with FH is about the same as the surrounding population. Furthermore, no controlled, randomized cholesterol-lowering trial restricted to those with FH has demonstrated a positive outcome. On the other hand, a number of studies suggest that increased thrombogenic factors—either procoagulant or those that lead to high platelet reactivity—may be the primary risk factors in FH. Those individuals who die prematurely have either higher lipoprotein (a) (Lp(a)), higher factor VIII and/or higher fibrinogen compared with those with a normal lifespan, whereas their LDL-C does not differ. Conclusions: Many observational and experimental studies have demonstrated that high LDL-C cannot be the cause of premature cardiovascular mortality among people with FH. The number who die early is also much smaller than expected. Apparently, some individuals with FH may have inherited other, more important risk factors than a high LDL-C. In accordance with this, our review has shown that increased coagulation factors are the commonest cause, but there may be other ones as well. MDPI 2022-08-15 /pmc/articles/PMC9409002/ /pubmed/36012410 http://dx.doi.org/10.3390/ijms23169146 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 Ravnskov, Uffe de Lorgeril, Michel Kendrick, Malcolm Diamond, David M. Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia |
title | Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia |
title_full | Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia |
title_fullStr | Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia |
title_full_unstemmed | Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia |
title_short | Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia |
title_sort | importance of coagulation factors as critical components of premature cardiovascular disease in familial hypercholesterolemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409002/ https://www.ncbi.nlm.nih.gov/pubmed/36012410 http://dx.doi.org/10.3390/ijms23169146 |
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