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Licensed Unlicensed Requires Authentication Published by De Gruyter February 23, 2021

Caveat emptor – hidden pitfalls in defining the 99th percentile of cardiac troponin assays

Paul Collinson ORCID logo EMAIL logo and Fred S. Apple

Corresponding author: Professor Paul Collinson, Department of Cardiology, Clinical Blood Sciences, St George’s University Hospitals NHS Foundation Trust and St George’s University of London, Cranmer Terrace, London SW17 0QT, UK, E-mail:

  1. Research funding: None declared.

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

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board or equivalent committee.


1. Sandoval, Y, Apple, FS, Saenger, AK, Collinson, PO, Wu, AHB, Jaffe, AS. 99th percentile upper-reference limit of cardiac troponin and the diagnosis of acute myocardial infarction. Clin Chem 2020;66:1167–80. in Google Scholar

2. Apple, FS, Jaffe, AS, Collinson, P, Mockel, M, Ordonez-Llanos, J, Lindahl, B, et al.. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem 2015;48:201–3. in Google Scholar

3. 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. in Google Scholar

4. 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. in Google Scholar

5. 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. in Google Scholar

6. Apple, FS, Wu, AHB, Sandoval, Y, Sexter, A, Love, SA, Myers, G, et al.. Sex-specific 99th percentile upper reference limits for high sensitivity cardiac troponin assays derived using a universal sample bank. Clin Chem 2020;66:434–44. in Google Scholar

7. Eggers, KM, Apple, FS, Lind, L, Lindahl, B. The applied statistical approach highly influences the 99th percentile of cardiac troponin I. Clin Biochem 2016;49:1109–12. in Google Scholar

8. Hickman, PE, Koerbin, G, Potter, JM, Glasgow, N, Cavanaugh, JA, Abhayaratna, WP, et al.. Choice of statistical tools for outlier removal causes substantial changes in analyte reference intervals in healthy populations. Clin Chem 2020;66:1558–61. in Google Scholar

Received: 2021-01-14
Accepted: 2021-02-15
Published Online: 2021-02-23
Published in Print: 2021-08-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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