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Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mut...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567405/ https://www.ncbi.nlm.nih.gov/pubmed/28549500 http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.015 |
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author | Sharifi, Mahtab Higginson, Elizabeth Bos, Sven Gallivan, Angela Harvey, Darren Li, Ka Wah Abeysekera, Amali Haddon, Angela Ashby, Helen Shipman, Kate E. Cooper, Jackie A. Futema, Marta Roeters van Lennep, Jeanine E. Sijbrands, Eric J.G. Labib, Mourad Nair, Devaki Humphries, Steve E. |
author_facet | Sharifi, Mahtab Higginson, Elizabeth Bos, Sven Gallivan, Angela Harvey, Darren Li, Ka Wah Abeysekera, Amali Haddon, Angela Ashby, Helen Shipman, Kate E. Cooper, Jackie A. Futema, Marta Roeters van Lennep, Jeanine E. Sijbrands, Eric J.G. Labib, Mourad Nair, Devaki Humphries, Steve E. |
author_sort | Sharifi, Mahtab |
collection | PubMed |
description | BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. We assessed the degree of preclinical atherosclerosis in treated patients with monogenic FH versus polygenic hypercholesterolemia. METHODS: FH mutation testing and genotypes of six LDL-C-associated single nucleotide polymorphisms (SNPs) were determined using routine methods. Those with a detected mutation (monogenic) and mutation-negative patients with LDL-C SNP score in the top two quartiles (polygenic) were recruited. Carotid intima media thickness (IMT) was measured by B-mode ultrasound and the coronary artery calcium (CAC) score was performed in three lipid clinics in the UK and the Netherlands. RESULTS: 86 patients (56 monogenic FH, 30 polygenic) with carotid IMT measurement, and 166 patients (124 monogenic, 42 polygenic) with CAC score measurement were examined. After adjustment for age and gender, the mean of all the carotid IMT measurements and CAC scores were significantly greater in the monogenic than the polygenic patients [carotid IMT mean (95% CI): 0.74 mm (0.7–0.79) vs. 0.66 mm (0.61–0.72), p = 0.038 and CAC score mean (95%): 24.5 (14.4–41.8) vs. 2.65 (0.94–7.44), p = 0.0004]. CONCLUSIONS: In patients with a diagnosis of FH, those with a monogenic cause have a higher severity of carotid and coronary preclinical atherosclerosis than those with a polygenic aetiology. |
format | Online Article Text |
id | pubmed-5567405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-55674052017-08-30 Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia Sharifi, Mahtab Higginson, Elizabeth Bos, Sven Gallivan, Angela Harvey, Darren Li, Ka Wah Abeysekera, Amali Haddon, Angela Ashby, Helen Shipman, Kate E. Cooper, Jackie A. Futema, Marta Roeters van Lennep, Jeanine E. Sijbrands, Eric J.G. Labib, Mourad Nair, Devaki Humphries, Steve E. Atherosclerosis Article BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. We assessed the degree of preclinical atherosclerosis in treated patients with monogenic FH versus polygenic hypercholesterolemia. METHODS: FH mutation testing and genotypes of six LDL-C-associated single nucleotide polymorphisms (SNPs) were determined using routine methods. Those with a detected mutation (monogenic) and mutation-negative patients with LDL-C SNP score in the top two quartiles (polygenic) were recruited. Carotid intima media thickness (IMT) was measured by B-mode ultrasound and the coronary artery calcium (CAC) score was performed in three lipid clinics in the UK and the Netherlands. RESULTS: 86 patients (56 monogenic FH, 30 polygenic) with carotid IMT measurement, and 166 patients (124 monogenic, 42 polygenic) with CAC score measurement were examined. After adjustment for age and gender, the mean of all the carotid IMT measurements and CAC scores were significantly greater in the monogenic than the polygenic patients [carotid IMT mean (95% CI): 0.74 mm (0.7–0.79) vs. 0.66 mm (0.61–0.72), p = 0.038 and CAC score mean (95%): 24.5 (14.4–41.8) vs. 2.65 (0.94–7.44), p = 0.0004]. CONCLUSIONS: In patients with a diagnosis of FH, those with a monogenic cause have a higher severity of carotid and coronary preclinical atherosclerosis than those with a polygenic aetiology. Elsevier 2017-08 /pmc/articles/PMC5567405/ /pubmed/28549500 http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.015 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sharifi, Mahtab Higginson, Elizabeth Bos, Sven Gallivan, Angela Harvey, Darren Li, Ka Wah Abeysekera, Amali Haddon, Angela Ashby, Helen Shipman, Kate E. Cooper, Jackie A. Futema, Marta Roeters van Lennep, Jeanine E. Sijbrands, Eric J.G. Labib, Mourad Nair, Devaki Humphries, Steve E. Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
title | Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
title_full | Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
title_fullStr | Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
title_full_unstemmed | Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
title_short | Greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
title_sort | greater preclinical atherosclerosis in treated monogenic familial hypercholesterolemia vs. polygenic hypercholesterolemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567405/ https://www.ncbi.nlm.nih.gov/pubmed/28549500 http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.015 |
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