Cardiac Troponin T and Troponin I in the General Population.
Adult
Aged
Cardiovascular Diseases
/ blood
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Predictive Value of Tests
Prognosis
Risk Assessment
Risk Factors
Scotland
/ epidemiology
Time Factors
Troponin I
/ blood
Troponin T
/ blood
cardiovascular diseases
genetics
risk factors
troponin
troponin T
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
11 06 2019
11 06 2019
Historique:
pubmed:
25
4
2019
medline:
17
3
2020
entrez:
25
4
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31014085
doi: 10.1161/CIRCULATIONAHA.118.038529
pmc: PMC6571179
doi:
Substances chimiques
Troponin I
0
Troponin T
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2754-2764Subventions
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/16/14/32023
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ASM/14/1
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZD/16/6
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ASM/14/01
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/13/1/30181
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127592696
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Références
Blood. 2006 Mar 1;107(5):1903-7
pubmed: 16304051
BMC Med Genet. 2006 Oct 02;7:74
pubmed: 17014726
Heart. 2007 Feb;93(2):172-6
pubmed: 17090561
Bioinformatics. 2007 May 15;23(10):1294-6
pubmed: 17384015
Circ Res. 1991 Nov;69(5):1226-33
pubmed: 1934353
J Investig Med. 2009 Dec;57(8):849-55
pubmed: 19952892
Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1269-75
pubmed: 20299689
JAMA. 2010 Dec 8;304(22):2503-12
pubmed: 21139111
J Am Coll Cardiol. 2011 Oct 18;58(17):1819-24
pubmed: 21962825
Nat Methods. 2011 Dec 04;9(2):179-81
pubmed: 22138821
Int J Epidemiol. 2013 Jun;42(3):689-700
pubmed: 22786799
Nat Genet. 2012 Oct;44(10):1166-70
pubmed: 22983301
Int J Cardiol. 2013 Sep 20;168(1):76-9
pubmed: 23041008
Circ Cardiovasc Genet. 2013 Feb;6(1):82-8
pubmed: 23247143
Nat Methods. 2013 Jan;10(1):5-6
pubmed: 23269371
Hypertension. 2013 Mar;61(3):602-8
pubmed: 23381795
J Renin Angiotensin Aldosterone Syst. 2014 Dec;15(4):319-28
pubmed: 23386283
Brief Bioinform. 2015 Jan;16(1):39-44
pubmed: 24008273
PLoS One. 2014 Mar 04;9(3):e90063
pubmed: 24594734
PLoS Genet. 2014 Apr 17;10(4):e1004234
pubmed: 24743097
J Am Coll Cardiol. 2014 Jun 10;63(22):2411-20
pubmed: 24747102
Hum Mol Genet. 2014 Sep 15;23(R1):R89-98
pubmed: 25064373
Circ Cardiovasc Genet. 2015 Feb;8(1):122-30
pubmed: 25561047
BMJ. 2015 Jan 21;350:g7873
pubmed: 25609052
Br J Anaesth. 2015 Jun;114(6):909-18
pubmed: 25740400
BMC Genomics. 2015 Jun 06;16:437
pubmed: 26048416
Sci Transl Med. 2015 Jun 17;7(292):292ra99
pubmed: 26084806
Eur Heart J. 2016 Jan 14;37(3):267-315
pubmed: 26320110
Circ Cardiovasc Genet. 2016 Feb;9(1):6-13
pubmed: 26787432
Atherosclerosis. 2016 Apr;247:135-41
pubmed: 26917225
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Thromb Haemost. 2016 Nov 30;116(6):1041-1049
pubmed: 27656708
J Am Coll Cardiol. 2016 Dec 27;68(25):2719-2728
pubmed: 28007133
J Am Coll Cardiol. 2017 Aug 1;70(5):558-568
pubmed: 28750699
Mol Psychiatry. 2017 Oct;22(10):1376-1384
pubmed: 28937693
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Transl Psychiatry. 2017 Nov 30;7(11):1263
pubmed: 29187746
Clin Chem. 2018 Nov;64(11):1607-1616
pubmed: 30126950
J Biol Chem. 1997 Jul 11;272(28):17542-50
pubmed: 9211900