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Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes

BACKGROUND: There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We...

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Autores principales: Welsh, Paul, Preiss, David, Hayward, Caroline, Shah, Anoop S.V., McAllister, David, Briggs, Andrew, Boachie, Charles, McConnachie, Alex, Padmanabhan, Sandosh, Welsh, Claire, Woodward, Mark, Campbell, Archie, Porteous, David, Mills, Nicholas L., Sattar, Naveed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571179/
https://www.ncbi.nlm.nih.gov/pubmed/31014085
http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038529
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author Welsh, Paul
Preiss, David
Hayward, Caroline
Shah, Anoop S.V.
McAllister, David
Briggs, Andrew
Boachie, Charles
McConnachie, Alex
Padmanabhan, Sandosh
Welsh, Claire
Woodward, Mark
Campbell, Archie
Porteous, David
Mills, Nicholas L.
Sattar, Naveed
author_facet Welsh, Paul
Preiss, David
Hayward, Caroline
Shah, Anoop S.V.
McAllister, David
Briggs, Andrew
Boachie, Charles
McConnachie, Alex
Padmanabhan, Sandosh
Welsh, Claire
Woodward, Mark
Campbell, Archie
Porteous, David
Mills, Nicholas L.
Sattar, Naveed
author_sort Welsh, Paul
collection PubMed
description BACKGROUND: There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We aimed to compare and contrast (1) the association of cTnT and cTnI with CVD and non-CVD outcomes, and (2) their determinants in a genome-wide association study. METHODS: High-sensitivity cTnT and cTnI were measured in serum from 19 501 individuals in Generation Scotland Scottish Family Health Study. Median follow-up was 7.8 years (quartile 1 to quartile 3, 7.1–9.2). Associations of each troponin with a composite CVD outcome (1177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined by using Cox models. A genome-wide association study was conducted using a standard approach developed for the cohort. RESULTS: Both cTnI and cTnT were strongly associated with CVD risk in unadjusted models. After adjusting for classical risk factors, the hazard ratio for a 1 SD increase in log transformed troponin was 1.24 (95% CI, 1.17–1.32) and 1.11 (1.04–1.19) for cTnI and cTnT, respectively; ratio of hazard ratios 1.12 (1.04–1.21). cTnI, but not cTnT, was associated with myocardial infarction and coronary heart disease. Both cTnI and cTnT had strong associations with CVD death and heart failure. By contrast, cTnT, but not cTnI, was associated with non-CVD death; ratio of hazard ratios 0.77 (0.67–0.88). We identified 5 loci (53 individual single-nucleotide polymorphisms) that had genome-wide significant associations with cTnI, and a different set of 4 loci (4 single-nucleotide polymorphisms) for cTnT. CONCLUSIONS: The upstream genetic causes of low-grade elevations in cTnI and cTnT appear distinct, and their associations with outcomes also differ. Elevations in cTnI are more strongly associated with some CVD outcomes, whereas cTnT is more strongly associated with the risk of non-CVD death. These findings help inform the selection of an optimal troponin assay for future clinical care and research in this setting.
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spelling pubmed-65711792019-07-22 Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes Welsh, Paul Preiss, David Hayward, Caroline Shah, Anoop S.V. McAllister, David Briggs, Andrew Boachie, Charles McConnachie, Alex Padmanabhan, Sandosh Welsh, Claire Woodward, Mark Campbell, Archie Porteous, David Mills, Nicholas L. Sattar, Naveed Circulation Original Research Articles BACKGROUND: There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We aimed to compare and contrast (1) the association of cTnT and cTnI with CVD and non-CVD outcomes, and (2) their determinants in a genome-wide association study. METHODS: High-sensitivity cTnT and cTnI were measured in serum from 19 501 individuals in Generation Scotland Scottish Family Health Study. Median follow-up was 7.8 years (quartile 1 to quartile 3, 7.1–9.2). Associations of each troponin with a composite CVD outcome (1177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined by using Cox models. A genome-wide association study was conducted using a standard approach developed for the cohort. RESULTS: Both cTnI and cTnT were strongly associated with CVD risk in unadjusted models. After adjusting for classical risk factors, the hazard ratio for a 1 SD increase in log transformed troponin was 1.24 (95% CI, 1.17–1.32) and 1.11 (1.04–1.19) for cTnI and cTnT, respectively; ratio of hazard ratios 1.12 (1.04–1.21). cTnI, but not cTnT, was associated with myocardial infarction and coronary heart disease. Both cTnI and cTnT had strong associations with CVD death and heart failure. By contrast, cTnT, but not cTnI, was associated with non-CVD death; ratio of hazard ratios 0.77 (0.67–0.88). We identified 5 loci (53 individual single-nucleotide polymorphisms) that had genome-wide significant associations with cTnI, and a different set of 4 loci (4 single-nucleotide polymorphisms) for cTnT. CONCLUSIONS: The upstream genetic causes of low-grade elevations in cTnI and cTnT appear distinct, and their associations with outcomes also differ. Elevations in cTnI are more strongly associated with some CVD outcomes, whereas cTnT is more strongly associated with the risk of non-CVD death. These findings help inform the selection of an optimal troponin assay for future clinical care and research in this setting. Lippincott Williams & Wilkins 2019-06-11 2019-04-24 /pmc/articles/PMC6571179/ /pubmed/31014085 http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038529 Text en © 2019 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
spellingShingle Original Research Articles
Welsh, Paul
Preiss, David
Hayward, Caroline
Shah, Anoop S.V.
McAllister, David
Briggs, Andrew
Boachie, Charles
McConnachie, Alex
Padmanabhan, Sandosh
Welsh, Claire
Woodward, Mark
Campbell, Archie
Porteous, David
Mills, Nicholas L.
Sattar, Naveed
Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes
title Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes
title_full Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes
title_fullStr Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes
title_full_unstemmed Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes
title_short Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations With Outcomes
title_sort cardiac troponin t and troponin i in the general population: comparing and contrasting their genetic determinants and associations with outcomes
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571179/
https://www.ncbi.nlm.nih.gov/pubmed/31014085
http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038529
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