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Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population

Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, however, due to the lack of routine monitoring, the pathology remains severely under-diagnosed and prevalence in the general population is not known. We have developed a set of machine learning metho...

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Autores principales: Sethi, Anurag, Taylor, D. Leland, Ruby, J. Graham, Venkataraman, Jagadish, Sorokin, Elena, Cule, Madeleine, Melamud, Eugene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582957/
https://www.ncbi.nlm.nih.gov/pubmed/36277789
http://dx.doi.org/10.3389/fcvm.2022.1003246
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author Sethi, Anurag
Taylor, D. Leland
Ruby, J. Graham
Venkataraman, Jagadish
Sorokin, Elena
Cule, Madeleine
Melamud, Eugene
author_facet Sethi, Anurag
Taylor, D. Leland
Ruby, J. Graham
Venkataraman, Jagadish
Sorokin, Elena
Cule, Madeleine
Melamud, Eugene
author_sort Sethi, Anurag
collection PubMed
description Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, however, due to the lack of routine monitoring, the pathology remains severely under-diagnosed and prevalence in the general population is not known. We have developed a set of machine learning methods to quantitate levels of abdominal aortic calcification (AAC) in the UK Biobank imaging cohort and carried out the largest to-date analysis of genetic, biochemical, and epidemiological risk factors associated with the pathology. In a genetic association study, we identified three novel loci associated with AAC (FGF9, NAV9, and APOE), and replicated a previously reported association at the TWIST1/HDAC9 locus. We find that AAC is a highly prevalent pathology, with ~ 1 in 10 adults above the age of 40 showing significant levels of hydroxyapatite build-up (Kauppila score > 3). Presentation of AAC was strongly predictive of future cardiovascular events including stenosis of precerebral arteries (HR~1.5), myocardial infarction (HR~1.3), ischemic heart disease (HR~1.3), as well as other diseases such as chronic obstructive pulmonary disease (HR~1.3). Significantly, we find that the risk for myocardial infarction from elevated AAC (HR ~1.4) was comparable to the risk of hypercholesterolemia (HR~1.4), yet most people who develop AAC are not hypercholesterolemic. Furthermore, the overwhelming majority (98%) of individuals who develop pathology do so in the absence of known pre-existing risk conditions such as chronic kidney disease and diabetes (0.6% and 2.7% respectively). Our findings indicate that despite the high cardiovascular risk, calcification of large arteries remains a largely under-diagnosed lethal condition, and there is a clear need for increased awareness and monitoring of the pathology in the general population.
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spelling pubmed-95829572022-10-21 Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population Sethi, Anurag Taylor, D. Leland Ruby, J. Graham Venkataraman, Jagadish Sorokin, Elena Cule, Madeleine Melamud, Eugene Front Cardiovasc Med Cardiovascular Medicine Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, however, due to the lack of routine monitoring, the pathology remains severely under-diagnosed and prevalence in the general population is not known. We have developed a set of machine learning methods to quantitate levels of abdominal aortic calcification (AAC) in the UK Biobank imaging cohort and carried out the largest to-date analysis of genetic, biochemical, and epidemiological risk factors associated with the pathology. In a genetic association study, we identified three novel loci associated with AAC (FGF9, NAV9, and APOE), and replicated a previously reported association at the TWIST1/HDAC9 locus. We find that AAC is a highly prevalent pathology, with ~ 1 in 10 adults above the age of 40 showing significant levels of hydroxyapatite build-up (Kauppila score > 3). Presentation of AAC was strongly predictive of future cardiovascular events including stenosis of precerebral arteries (HR~1.5), myocardial infarction (HR~1.3), ischemic heart disease (HR~1.3), as well as other diseases such as chronic obstructive pulmonary disease (HR~1.3). Significantly, we find that the risk for myocardial infarction from elevated AAC (HR ~1.4) was comparable to the risk of hypercholesterolemia (HR~1.4), yet most people who develop AAC are not hypercholesterolemic. Furthermore, the overwhelming majority (98%) of individuals who develop pathology do so in the absence of known pre-existing risk conditions such as chronic kidney disease and diabetes (0.6% and 2.7% respectively). Our findings indicate that despite the high cardiovascular risk, calcification of large arteries remains a largely under-diagnosed lethal condition, and there is a clear need for increased awareness and monitoring of the pathology in the general population. Frontiers Media S.A. 2022-10-06 /pmc/articles/PMC9582957/ /pubmed/36277789 http://dx.doi.org/10.3389/fcvm.2022.1003246 Text en Copyright © 2022 Sethi, Taylor, Ruby, Venkataraman, Sorokin, Cule and Melamud. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Sethi, Anurag
Taylor, D. Leland
Ruby, J. Graham
Venkataraman, Jagadish
Sorokin, Elena
Cule, Madeleine
Melamud, Eugene
Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
title Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
title_full Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
title_fullStr Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
title_full_unstemmed Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
title_short Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
title_sort calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582957/
https://www.ncbi.nlm.nih.gov/pubmed/36277789
http://dx.doi.org/10.3389/fcvm.2022.1003246
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