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High-sensitivity cardiac troponin I in the general population – defining reference populations for the determination of the 99th percentile in the Gutenberg Health Study

  • Tanja Zeller EMAIL logo , Francisco Ojeda , Fabian J. Brunner , Philipp Peitsmeyer , Thomas Münzel , Harald Binder , Norbert Pfeiffer , Matthias Michal , Philipp S. Wild , Stefan Blankenberg and Karl J. Lackner EMAIL logo
Published/Copyright: October 6, 2014

Abstract

Background: The 99th percentile of cardiac troponin levels, determined in a reference population, is accepted as threshold for diagnosis of acute myocardial infarction (AMI). However, there is no common consensus of how to define the reference population. The aim of the present study was to determine 99th percentile reference values, determined by a high-sensitivity assay (hsTnI), according to different health status and cardiovascular risk factor prevalence in a large population-based sample.

Methods: Troponin I was determined using the Abbott ARCHITECT STAT highly sensitive troponin I immunoassay in 4138 participants of the Gutenberg Health Study.

Results: hsTnI was detectable in 81.6% of all individuals. The 99th percentile of the overall population was 27 ng/L. Age and gender had a prominent influence on these values. Exclusion of individuals with elevated natriuretic peptide levels or cardiac abnormalities resulted in lower 99th percentile values, whereas exclusion of individuals with an impaired estimated glomerular filtration rate (eGFR) or with prevalent coronary artery disease/myocardial infarction (CAD/MI) did not result in a meaningful change.

Conclusions: Troponin I, measured by a high-sensitivity assay, can be reliably detected in the vast majority of the general population. hsTnI values were dependent on age, gender as well as structural and functional cardiac abnormalities.


Corresponding authors: Tanja Zeller, Clinic of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany, Phone: +49 40 741056575, E-mail: ; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany; and Karl J. Lackner, Department of Laboratory Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany, Phone: +49 6131 177190, E-mail:

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: Abbott Diagnostics provided test reagents for high-sensitive troponin I determinations within the frame of the Gutenberg Health Study. This work has been supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. HEALTH-F2-2011-278913 (BiomarCaRE). Stefan Blankenberg has received honoraria from Abbott Diagnostics, Siemens, Brahms/Thermo Fisher, and Roche Diagnostics and is a consultant for Thermo Fisher.

Employment or leadership: None declared.

Honorarium: Karl J. Lackner has received honorari from Abbott Diagnostics, Siemens and bioMérieux.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. 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;60:1581–98.10.1016/j.jacc.2012.08.001Search in Google Scholar PubMed

2. Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009;361:868–77.10.1056/NEJMoa0903515Search in Google Scholar PubMed

3. Keller T, Zeller T, Ojeda F, Tzikas S, Lillpopp L, Sinning C, et al. Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. J Am Med Assoc 2011;306:2684–93.10.1001/jama.2011.1896Search in Google Scholar PubMed

4. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361: 858–67.10.1056/NEJMoa0900428Search in Google Scholar PubMed

5. Mueller M, Biener M, Vafaie M, Doerr S, Keller T, Blankenberg S, et al. Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in acute coronary syndrome and in patients with increased troponin in the absence of acute coronary syndrome. Clin Chem 2012;58:209–18.10.1373/clinchem.2011.171827Search in Google Scholar PubMed

6. Christ M, Bertsch T, Popp S, Bahrmann P, Heppner HJ, Muller C. High-sensitivity troponin assays in the evaluation of patients with acute chest pain in the emergency department. Clin Chem Lab Med 2011;49:1955–63.10.1515/CCLM.2011.695Search in Google Scholar PubMed

7. Omland T, Pfeffer MA, Solomon SD, de Lemos JA, Rosjo H, Saltyte Benth J, et al. Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease. J Am Coll Cardiol 2013;61:1240–9.10.1016/j.jacc.2012.12.026Search in Google Scholar PubMed

8. Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009;361:2538–47.10.1056/NEJMoa0805299Search in Google Scholar PubMed PubMed Central

9. Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 2011;123:1367–76.10.1161/CIRCULATIONAHA.110.005264Search in Google Scholar PubMed PubMed Central

10. Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574–81.10.1373/clinchem.2012.192716Search in Google Scholar PubMed

11. de Lemos JA, Drazner MH, Omland T, Ayers CR,Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. J Am Med Assoc 2010;304:2503–12.10.1001/jama.2010.1768Search in Google Scholar PubMed PubMed Central

12. deFilippi CR, de Lemos JA, Christenson RH, Gottdiener JS, Kop WJ, Zhan M, et al. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. J Am Med Assoc 2010;304:2494–502.10.1001/jama.2010.1708Search in Google Scholar PubMed PubMed Central

13. Everett BM, Cook NR, Magnone MC, Bobadilla M, Kim E, Rifai N, et al. Sensitive cardiac troponin T assay and the risk of incident cardiovascular disease in women with and without diabetes mellitus: the Women’s Health Study. Circulation. 2011;123:2811–8.10.1161/CIRCULATIONAHA.110.009928Search in Google Scholar PubMed PubMed Central

14. Zeller T, Tunstall-Pedoe H, Saarela O, Ojeda F, Schnabel RB, Tuovinen T, et al. High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort. Eur Heart J 2014;35:271–81.10.1093/eurheartj/eht406Search in Google Scholar PubMed

15. Collinson PO, Heung YM, Gaze D, Boa F, Senior R, Christenson R, et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem 2012;58:219–25.10.1373/clinchem.2011.171082Search in Google Scholar PubMed

16. McKie PM, Heublein DM, Scott CG, Gantzer ML, Mehta RA, Rodeheffer RJ, et al. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem 2013;59:1099–107.10.1373/clinchem.2012.198614Search in Google Scholar PubMed

17. Wild PS, Sinning CR, Roth A, Wilde S, Schnabel RB, Lubos E, et al. Distribution and categorization of left ventricular measurements in the general population: results from the population-based Gutenberg Heart Study. Circ Cardiovasc Imaging 2010;3:604–13.10.1161/CIRCIMAGING.109.911933Search in Google Scholar PubMed

18. Wild PS, Zeller T, Beutel M, Blettner M, Dugi KA, Lackner KJ, et al. [The Gutenberg Health Study]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2012;55:824–9.10.1007/s00103-012-1502-7Search in Google Scholar PubMed

19. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–12.10.7326/0003-4819-150-9-200905050-00006Search in Google Scholar PubMed PubMed Central

20. Dorfman AH. Inference on distribution functions and quantiles. In: Pfeffermann D, Rao CR, editors. Handbook of Statistics 29: Sample surveys: design, methods and applications, Chapter 36. Amsterdam: North Holland, 1994.Search in Google Scholar

21. Koerbin G, Abhayaratna WP, Potter JM, Apple FS, Jaffe AS, Ravalico TH, et al. Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays. Clin Biochem 2013;46:1636–43.10.1016/j.clinbiochem.2013.08.004Search in Google Scholar PubMed

22. Eggers KM, Lind L, Venge P, Lindahl B. Factors influencing the 99th percentile of cardiac troponin I evaluated in community-dwelling individuals at 70 and 75 years of age. Clin Chem 2013;59:1068–73.10.1373/clinchem.2012.196634Search in Google Scholar PubMed

23. Chenevier-Gobeaux C, Bailleul S, Mzabi A, Blanc MC, Lefevre G. Upper reference limits of high-sensitivity cardiac troponin T in a general population: comparison with those of sensitive cardiac troponin I. Clin Lab 2013;59:333–6.10.7754/Clin.Lab.2012.120230Search in Google Scholar

24. Hickman PE, Badrick T, Wilson SR, McGill D. Reporting of cardiac troponin – problems with the 99th population percentile. Clin Chim Acta 2007;381:182–3.10.1016/j.cca.2007.03.012Search in Google Scholar PubMed


Supplemental Material

The online version of this article (DOI: 10.1515/cclm-2014-0619) offers supplementary material, available to authorized users.


Received: 2014-6-12
Accepted: 2014-9-11
Published Online: 2014-10-6
Published in Print: 2015-4-1

©2015 by De Gruyter

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