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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)....

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Autores principales: Ravnskov, Uffe, de Lorgeril, Michel, Kendrick, Malcolm, Diamond, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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