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, 139(24), pp. 2754-2764. (doi: 10.1161/CIRCULATIONAHA.118.038529) (PMID:31014085) (PMCID:PMC6571179)

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: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McConnachie, Professor Alex and Welsh, Professor Paul and McAllister, Professor David and Preiss, Dr David and Boachie, Mr Charles and Padmanabhan, Professor Sandosh and Briggs, Professor Andrew 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 > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health; College of Medical Veterinary and Life Sciences > School of Health & 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 139(24):2754-2764
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
68092	1	Cardiac biomarkers and the prediction of CVD in Scotland	Paul Welsh	Office of the Chief Scientist (CSO)	ASM/14/1	RI CARDIOVASCULAR & MEDICAL SCIENCES