Abstract
Objectives
Upper reference limits of high-sensitivity cardiac troponin T (hs-cTnT) are derived from healthy, population-based cohorts, and are frequently exceeded in hospitalized patients. In this study we aim to systematically examine the differences between in-hospital patients with no diagnosed cardiac diseases and a population-based cohort.
Methods
Retrospective analyses were performed in two independent cohorts. We included 5,652 participants of the prospective population-based LIFE cohort as well as 9,300 patients having been treated at our hospital between 2014 and 2021. In both cohorts, subjects with diagnosed or suspected cardiac diseases were excluded. We used Spearman’s rank correlation for correlation analyses of hs-cTnT serum concentrations and age. Sex- and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained in both cohorts.
Results
In both cohorts, hs-cTnT serum concentrations positively correlated with age. Male sex was associated with higher hs-cTnT serum concentrations. Persons treated in hospital showed significantly higher hs-cTnT concentrations in females and males aged above 50. While in the population-based cohort only 99th percentile hs-cTnT results of females aged above 70 and males aged above 60 years exceeded the assay’s upper reference limit, the 99th percentiles of in-hospital females over 40 years and males of all age groups exceeded this threshold.
Conclusions
Besides age and sex, hospitalization per se is correlated with higher serum concentrations of hs-cTnT in most age groups. Our results indicate, that unconditionally applying current hs-cTnT cut-offs to inpatients might overestimate myocardial infarction and potentially lead to overdiagnosis.
Funding source: RL eHealthSax 2017/18
Award Identifier / Grant number: 100331796
-
Research funding: This work was supported by LIFE, financed by the excellence initiative of the Saxony Ministry of Science and Art, Saxony, Germany and the European Regional Development Fund of the European Union. The project AMPEL is co-financed through public funds according to the budget decided by the Saxon State Parliament under the RL eHealthSax 2017/18 grant number 100331796.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Rolf Wachter declares research fundings by Boehringer Ingelheim, DMBF, DFG, European Union and Medtronic. He received consulting fees or honoraria by Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Medtronic, Novartis, Pharmacosmos, Pfizer, Sanofi, Servier and SOBI.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Collet, J-P, Thiele, H, Barbato, E, Barthélémy, O, Bauersachs, J, Bhatt, DL, et al.. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289–367. https://doi.org/10.1093/eurheartj/ehaa575.Search in Google Scholar PubMed
2. Giannitsis, E, Kurz, K, Hallermayer, K, Jarausch, J, Jaffe, AS, Katus, HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 2010;56:254–61. https://doi.org/10.1373/clinchem.2009.132654.Search in Google Scholar PubMed
3. Wu, AHB, Christenson, RH, Greene, DN, Jaffe, AS, Kavsak, PA, Ordonez-Llanos, J, et al.. Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the academy of the American association for clinical Chemistry and the task force on clinical applications of cardiac bio-markers of the international federation of clinical Chemistry and laboratory medicine. Clin Chem 2018;64:645–55. https://doi.org/10.1373/clinchem.2017.277186.Search in Google Scholar PubMed
4. Thygesen, K, Alpert, JS, Jaffe, AS, Simoons, ML, Chaitman, BR, White, HD, et al.. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012;60:1581–98. https://doi.org/10.1016/j.gheart.2012.08.001.Search in Google Scholar PubMed
5. Amsterdam, EA, Wenger, NK, Brindis, RG, Casey, DE, Ganiats, TG, Holmes, DR, et al.. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes. J Am Coll Cardiol 2014;64:e139–228. https://doi.org/10.1016/j.jacc.2014.09.017.Search in Google Scholar PubMed
6. Gärtner, C, Langhammer, R, Schmidt, M, Federbusch, M, Wirkner, K, Löffler, M, et al.. Revisited upper reference limits for highly sensitive cardiac troponin T in relation to age, sex, and renal function. JCM 2021;10:5508. https://doi.org/10.3390/jcm10235508.Search in Google Scholar PubMed PubMed Central
7. Pfortmueller, CA, Funk, G-C, Marti, G, Leichtle, AB, Fiedler, GM, Schwarz, C, et al.. Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency. Am J Cardiol 2013;112:1968–72. https://doi.org/10.1016/j.amjcard.2013.08.028.Search in Google Scholar PubMed
8. Aksoy, N, Ozer, O, Sari, I, Sucu, M, Aksoy, M, Geyikli, I. Contribution of renal function impairment to unexplained troponin T elevations in congestive heart failure. Ren Fail 2009;31:272–7. https://doi.org/10.1080/08860220902780119.Search in Google Scholar PubMed
9. Gaggin, HK, Dang, PV, Do, LD, deFilippi, CR, Christenson, RH, Lewandrowski, EL, et al.. Reference interval evaluation of high-sensitivity troponin T and N-terminal B-type natriuretic peptide in vietnam and the US: the north south east west trial. Clin Chem 2014;60:758–64. https://doi.org/10.1373/clinchem.2013.216275.Search in Google Scholar PubMed
10. Franzini, M, Lorenzoni, V, Masotti, S, Prontera, C, Chiappino, D, Latta, DD, et al.. The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: a multicenter study in Italy. Clin Chim Acta 2015;438:376–81. https://doi.org/10.1016/j.cca.2014.09.010.Search in Google Scholar PubMed
11. Gore, MO, Seliger, SL, deFilippi, CR, Nambi, V, Christenson, RH, Hashim, IA, et al.. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014;63:1441–8. https://doi.org/10.1016/j.jacc.2013.12.032.Search in Google Scholar PubMed PubMed Central
12. Hammarsten, O, Fu, MLX, Sigurjonsdottir, R, Petzold, M, Said, L, Landin-Wilhelmsen, K, et al.. Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction. Clin Chem 2012;58:628–37. https://doi.org/10.1373/clinchem.2011.171496.Search in Google Scholar PubMed
13. Potter, JM, Simpson, AJ, Kerrigan, J, Southcott, E, Salib, MM, Koerbin, G, et al.. Cross-sectional study of high-sensitivity cardiac troponins T and I in a hospital and community outpatient setting. Clin Biochem 2017;50:105–9. https://doi.org/10.1016/j.clinbiochem.2016.10.011.Search in Google Scholar PubMed
14. Mariathas, M, Allan, R, Ramamoorthy, S, Olechowski, B, Hinton, J, Azor, M, et al.. True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study. BMJ 2019;364:l729.10.1136/bmj.l729Search in Google Scholar PubMed PubMed Central
15. Loeffler, M, Engel, C, Ahnert, P, Alfermann, D, Arelin, K, Baber, R, et al.. The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany. BMC Publ Health 2015;15:691. https://doi.org/10.1186/s12889-015-1983-z.Search in Google Scholar PubMed PubMed Central
16. Levey, AS, Stevens, LA, Schmid, CH, Zhang, YL, Castro, AF, Feldman, HI, et al.. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.Search in Google Scholar PubMed PubMed Central
17. Harris, CR, Millman, KJ, van der Walt, SJ, Gommers, R, Virtanen, P, Cournapeau, D, et al.. Array programming with NumPy. Nature 2020;585:357–62. https://doi.org/10.1038/s41586-020-2649-2.Search in Google Scholar PubMed PubMed Central
18. Höhle, M.: Compute confidence intervals for quantile [Internet]. Available from: https://github.com/hoehleatsu/quantileCI [Accessed 07 Sep 2021].Search in Google Scholar
19. R Core Team. R. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2014.Search in Google Scholar
20. Wickham, H. ggplot2: elegant graphics for data analysis. New York: Springer; 2016.10.1007/978-3-319-24277-4Search in Google Scholar
21. Murdoch, D, Adler, D. Rgl: 3D visualization using openGL [Internet]. 2017. Avaiable from: https://github.com/dmurdoch/rgl [Accessed 30 Sep 2021].Search in Google Scholar
22. van Rossum, GDFL. Python 3 reference manual. California, USA: Scotts Valley; 2009.Search in Google Scholar
23. Sharain, K, Vasile, VC, Sandoval, Y, Donato, LJ, Clements, CM, Newman, JS, et al.. The elevated high-sensitivity cardiac troponin T pilot. Mayo Clin Proc 2021;96:2366–75. https://doi.org/10.1016/j.mayocp.2021.01.027.Search in Google Scholar PubMed
24. Monneret, D, Gellerstedt, M, Bonnefont-Rousselot, D. Determination of age- and sex-specific 99th percentiles for high-sensitive troponin T from patients: an analytical imprecision- and partitioning-based approach. Clin Chem Lab Med 2018;56:685–96. https://doi.org/10.1515/cclm-2017-0256.Search in Google Scholar PubMed
25. Kuster, N, Monnier, K, Baptista, G, Dupuy, A-M, Badiou, S, Bargnoux, A-S, et al.. Estimation of age- and comorbidities-adjusted percentiles of high-sensitivity cardiac troponin T levels in the elderly. Clin Chem Lab Med 2015;53:691–8. https://doi.org/10.1515/cclm-2014-0121.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0040).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
