Cardiac troponin T and troponin I in the general population: comparing and contrasting their genetic determinants and associations with outcomes

Welsh, P. et al. (2019) Cardiac troponin T and troponin I in the general population: comparing and contrasting their genetic determinants and associations with outcomes. Circulation, (doi:10.1161/CIRCULATIONAHA.118.038529) (PMID:31014085) (Early Online Publication)

Welsh, P. et al. (2019) Cardiac troponin T and troponin I in the general population: comparing and contrasting their genetic determinants and associations with outcomes. Circulation, (doi:10.1161/CIRCULATIONAHA.118.038529) (PMID:31014085) (Early Online Publication)

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Abstract

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 i) the association of cTnT and cTnI with CVD and non-CVD outcomes, and ii) their determinants in a Genome wide association study (GWAS). 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 (Q1-Q3 7.1-9.2). Associations of each troponin with a composite CVD outcome (1,177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined 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 one standard deviation 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 HRs 1.12 (1.04-1.21). cTnI, but not cTnT, was associated with MI and CHD. 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 HRs 0.77 (0.67-0.88). We identified five loci (53 individual SNPs) that had GWAS significant associations with cTnI, and a different set of four loci (4 SNPs) 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 selection of an optimal troponin assay for future clinical care and research in this setting.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Preiss, Dr David and McConnachie, Dr Alex and Boachie, Mr Charles and Padmanabhan, Professor Sandosh and Welsh, Dr Paul and Briggs, Professor Andrew and McAllister, Dr David and Sattar, Professor Naveed and Welsh, Dr Claire
Authors: Welsh, P., Preiss, D., Hayward, C., Shah, A. S.V., McAllister, D., Briggs, A., Boachie, C., McConnachie, A., Padmanabhan, S., Welsh, C., Woodward, M., Campbell, A., Porteous, D., Mills, N. L., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Health Economics and Health Technology Assessment
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:24 April 2019
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Circulation 2019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
680921Cardiac biomarkers and the prediction of CVD in ScotlandPaul WelshChief Scientist office (CSO)ASM/14/1RI CARDIOVASCULAR & MEDICAL SCIENCES