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Licensed Unlicensed Requires Authentication Published by De Gruyter April 28, 2022

The intra-individual variation of cardiac troponin I: the effects of sex, age, climatic season, and time between samples

  • Gus Koerbin EMAIL logo , Julia M. Potter , Marcela Pinto do Nascimento , Louise Cullen , Samuel L. Scanlan , Catherine Woods and Peter E. Hickman



Knowing the intra-individual variation (CVi), also termed within subject biological variation, of an analyte is essential to properly interpret apparent changes in concentration. While there have been many studies assessing the CVi of cardiac troponin (cTnI), they have been limited in looking at CVi in different settings, and there is no data available on whether CVi might change in different settings.


We used our large cTnI data bank to look at the CVi of cTnI in Emergency Department (ED) patients who had an acute myocardial infarction event excluded. We looked at the effects of gender, age, climatic season, and time between samples to assess whether CVi changed. To assess the effect of age, after exclusion, we collected two samples from each subject for each study which were used to calculate the CVi between those identified groups. There were 139 males and 98 females aged <65 years and 109 males and 98 females aged ≥65 years. For gender and season, there were 122 males and 94 females in the summer period and 126 males and 102 females in the winter period. To assess long term variation there were 195 males and 153 females who had further admissions after more than 12 months.


For the four variables listed, there were no significant differences in within individual variation (CVi), but there was a significant difference in between individual variation (CVg) for men and women with regard to age. The Index of Individuality (II) was <0.20 for all conditions studied. We noted that >90% of subjects had an reference change value (RCV) <9 ng/L.


Because troponin concentration in patients without an identified cardiac condition change so little, delta changes are potentially of great value in assessing patients in the ED. Significant delta changes in troponin can occur without the 99th percentile being exceeded.

Corresponding author: Dr. Gus Koerbin, University of Canberra, Faculty of Health, Bruce, ACT 2605, Australia, Phone: +61 417 607 773, 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: This study was approved by the ACT Health Human Research Ethics Committee.


1. Thygesen, K, Alpert, JS, Jaffe, AS, Chaitman, BR, Bax, JJ. Fourth universal definition of myocardial infarction. J Am Coll Cardiol 2018;72:2231–64. in Google Scholar PubMed

2. Collinson, PO, Heung, YM, Gaze, D, Boa, F, Senior, R, Christensen, R, et al.. Influence of population selection on the 99th percentile values for cardiac troponin assays. Clin Chem 2012;58:219–25. in Google Scholar PubMed

3. 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. in Google Scholar PubMed

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 PubMed

5. Hickman, PE, Abhayaratna, WP, Potter, JM, Koerbin, G. Age-related differences in hs-cTnI concentration in healthy adults. Clin Biochem 2019;59:26–9. in Google Scholar PubMed

6. Cullen, L, Muller, C, Parsonage, WA, Wildi, K, Greenslade, JH, Twerenbold, R, et al.. Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome. J Am Coll Cardiol 2013;62:1242–9. in Google Scholar PubMed

7. Simpson, AJ, Potter, JM, Koerbin, G, Oakman, C, Cullen, L, Wilkes, GJ, et al.. Use of observed within-person variation of cardiac troponin in emergency department patients for determination of biological variation and percentage and absolute reference change values. Clin Chem 2014;60:848–54. in Google Scholar PubMed

8. Koerbin, G, Tate, J, Potter, JM, Cavanaugh, J, Glasgow, N, Hickman, PE. Characterisation of a highly sensitive troponin I assay and its application to a cardio-healthy population. Clin Chem Lab Med 2012;50:871–8. in Google Scholar PubMed

9. Abbott ARCHITECT STAT high sensitive troponin-I [package insert SP25-37]. Chicago, IL: Abbott Laboratories; 2018.Search in Google Scholar

10. Hickman, PE, Koerbin, G, Badrick, T, Oakman, C, Potter, JM. The importance of low-level QC for high sensitivity troponin assays. Clin Biochem 2018;58:60–3. in Google Scholar PubMed

11. Koerbin, GL, Potter, JM, Abhayaratna, WP, Telford, RD, Badrick, T, Apple, FS, et al.. Longitudinal studies of cardiac troponin I in a large cohort of healthy children. Clin Chem 2012;58:1665–72. in Google Scholar PubMed

12. Fokkema, MR, Herrmann, Z, Muskiet, FAJ, Moecks, J. Reference change values for brain natriuretic peptides revisited. Clin Chem 2006;52:1602–3. in Google Scholar PubMed

13. Harris, EK, Yasaka, T. On the calculation of a “reference change” for comparing two consecutive measurements. Clin Chem 1983;29:25–30. in Google Scholar

14. Badrick, T, Wilson, S, Dimeski, G, Hickman, PE. Objective determination of appropriate reporting intervals. Ann Clin Biochem 2004;41:385–90. in Google Scholar PubMed

15. Jones, GRD. Effect of the reporting-interval size on critical difference estimation: beyond “2.77.” Clin Chem 2006;52:880–5. in Google Scholar PubMed

16. Horowitz, GL, Altaie, A, Boyd, JC, Ceriotto, F, Garg, U, Horn, P, et al.. Defining, establishing, and verifying reference intervals in the clinical laboratory; ap- proved guideline, 3rd ed. Wayne, PA: CLSI; 2008. CLSI document no. EP28-A3c.Search in Google Scholar

17. Twerenbold, R, Neumann, JT, Sörensen, NA, Ojeda, F, Karakas, M, Boeddinghaus, J, et al.. Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction. J Am Coll Cardiol 2018;72:620–32. in Google Scholar PubMed

18. Petersen, PH, Sandberg, S, Fraser, CG, Goldsmidt, H. Influence of index of individuality on false positives in repeated sampling from healthy individuals. Clin Chem Lab Med 2001;39:160–5. in Google Scholar PubMed

19. 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. in Google Scholar PubMed

20. Neuman, JT, Sorrensen, NA, Schwemer, T, Ojeda, F, Bourry, R, Sciacca, V, et al.. Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm. J Am Med Assoc 2016;1:397–404. in Google Scholar PubMed

21. Pretorius, CJ, Cullen, L, Parsonage, WA, Greenslade, JH, Tate, JR, Wilgen, U, et al.. Towards a consistent definition of a significant delta troponin with z-scores: a way out of chaos? Eur Heart J Acute Cardiovasc Care 2014;3:149–57. in Google Scholar PubMed

22. Aakre, KM, Roraas, T, Petersen, PH, Svarstad, E, Sellevoll, H, Skadberg, O, et al.. Weekly and 90-minute biological variations in cardiac troponin T and cardiac troponin I in hemodialysis patients and healthy controls. Clin Chem 2014;60:838–47. in Google Scholar PubMed

23. Ceriotti, F, Dıaz-Garzon, MJ, Fernandez-Calle, P, Maregnani, A, Aarsand, AK, Coskun, A, et al.. European federation of clinical chemistry and laboratory medicine (EFLM) working group on biological variation. The European biological variation study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays. Clin Chem Lab Med 2020;58:1741–7. in Google Scholar PubMed

24. Nordenskjold, AM, Ahlstrom, H, Eggers, KM, Frobert, O, Jaffe, AS, Venge, P, et al.. Short- and long-term individual variation in cardiac troponin in patients with stable coronary artery disease. Clin Chem 2013;59:401–9. in Google Scholar PubMed

25. Diaz-Garzon, J, Fernandez-Calle, P, Sandberg, S, Ozcurumez, M, Bartlett, WA, Coskun, A, et al.. Biological variation of cardiac troponin in health and disease: a systematic review and meta-analysis. Clin Chem 2021;67:256–64.10.1093/clinchem/hvaa261Search in Google Scholar PubMed

26. Klinkenberg, LJJ, van Dijk, J-W, Tan, FES, van Loon, LJC, van Dieijen-Visser, MP, Meex, SJR. Circulating cardiac troponin T exhibits a diurnal rhythm. JACC 2014;63:1788-95 in Google Scholar PubMed

27. Apple, FS, Jaffe, AS. Clinical implications of a recent adjustment to the high-sensitivity cardiac troponin T assay: user beware. Clin Chem 2012;58:1599–600. in Google Scholar PubMed

28. Aarsand, AK, Roraas, T, Fernandez-Calle, P, Ricos, C, Diaz-Garzon, J, Jonker, N, et al.. The biological variation data critical appraisal checklist: a standard for evaluating studies on biological variation. Clin Chem 2018;64:501–14.10.1373/clinchem.2017.281808Search in Google Scholar PubMed

Received: 2022-02-13
Accepted: 2022-04-08
Published Online: 2022-04-28
Published in Print: 2022-06-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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