Comparison of troponin I (Abbott, Beckman Coulter, Siemens) and troponin T (Roche) high-sensitivity measurement results

Česká verze

Authors: A. Jabor ^1,2; Z. Kubíček ¹; J. Komrsková ^1,2; M. Labanczová ¹; T. Vacková ^1,2; S. Vaingátová ^1,2; D. Viczénová ¹; J. Vymětalík ¹; J. Franeková ^1,2
Authors place of work: IKEM, Pracoviště laboratorních metod, Praha ¹; Univerzita Karlova, 3. lékařská fakulta, Praha ²
Published in the journal: Klin. Biochem. Metab., 27, 2019, No. 2, p. 53-60

Summary

Objective: Our study is focused on comparing selected analytical characteristics of high-sensitivity methods for the measurement of cardiac troponin I (hs-cTnI) produced by Abbott, Beckman Coulter, and Siemens and cardiac troponin T (hs-cTnT) by Roche.

Design: A prospective study aimed to validate analytical characteristics, estimate the 99^th percentile, and compare the 99^th percentile multiples.

Settings: Institute for Clinical and Experimental Medicine, Department of Laboratory Methods, Prague, Czech Republic

Material and Methods: Analytical systems: Architect i2000 (Abbott), UniCel DxI 800 (Beckman Coulter), Cobas e801 (Roche), and ADVIA Centaur XP (Siemens). Diagnostic kits: STAT High Sensitive Troponin-I assay (Abbott; further hs-cTnI Abbott), ACCESS hsTnI (Beckman Coulter; further hs-cTnI Beckman Coulter), Elecsys hsTnT (STAT) (Roche; further hs-cTnT Roche), and ADVIA Centaur TNIH (Siemens; further hs-cTnI Siemens). Linearity was assessed according to Kroll. The precision study was performed according to the EP05-A2 protocol. Estimation of the 99^th percentile was performed utilizing three following approaches: the first was a nonparametric estimation with 90% confidence interval and with elimination of outliers according to Reed; the second was a procedure according to Harrell and Davis (jackknifed method) with elimination of outliers according to Reed; the third was a nonparametric estimation of the 99^th percentile (only the lower limit of 90% confidence interval was determined). The 99^th percentile multiples comparability assessment, with respect to type 4a and 5 myocardial infarction definitions, was performed on clinical samples using kappa statistics.

Results: Total precision determined according to the EP05-A2 protocol did not exceed 7% over a broad concentration range for all four methods (hs-cTnI Abbott, hs-cTnI Beckman Coulter, hs-cTnT Roche, and hs-cTnI Siemens). Linearity was proved for all four methods of hs-cTn measurement; however, quadratic function was optimal for hs-cTnT Roche. The estimation of the 99^th percentile (performed for hs-cTnI Abbott, hs-cTnI Beckman Coulter and hs-cTnT Roche only) showed significant differences between men and women and complied with manufacturers’ data. Determining the 99^th percentile according to Harrell and Davis (outliers excluded) is a possible way to estimate the 99^th percentile in reference groups with less than the recommended 299 individuals. Comparability of the 99^th percentile multiples was better between hs-cTnI Abbott and hs-cTnI Beckman Coulter; however, comparability was poor between hs-cTnI (Abbott, Beckman Coulter) and hs-cTnT Roche. Classification of the type 4a or 5 myocardial infarction depends on the diagnostic kit used.

Conclusion: We compared high-sensitivity measurement methods for troponin I (Abbott, Beckman Coulter, and Siemens) and troponin T (Roche) and proved sufficient precision of the measurement and linearity over a broad range of concentrations. We confirmed sex differences at the 99^th percentile of healthy persons and tested different statistical methods for estimation of the 99^th percentile and elimination of outliers. For the classification of patients, with respect to the type 4a and 5 myocardial infarction definition, we found only a borderline comparability among results of the different types of cTn concentration measurement methods. Results obtained by the diagnostic kits are reliable from the analytical point of view, but they are not interchangeable. The tested diagnostic kits offer reliable tools for the measurement of low concentrations of cardiac troponins enable, interpretation of small delta changes and strengthen clinical legitimacy of high-sensitivity methods of troponin concentration measurements.

Keywords:

Cardiac troponins – 99th percentile – clinical evaluation

Zdroje

1. Thygesen, K., Alpert, J. S., Jaffe, A. S. et al. Fourth universal definition of myocardial infarction (2018). Eur. Heart. J., 2019, 40, 3, 237-269.

2. IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB). High-Sensitivity* Cardiac Troponin I and T Assay Analytical Characteristics Designated by Manufacturer, v012019. Dostupné z http://www.ifcc.org/media/477656/high-sensitivity-cardiac-troponin-i-and-t-assay-analytical-characteristics-designated-by-manufacturer-v012019.pdf (Přístup 25.1.2019).

3. Kroll, M. H., Praestgaard, J., Michaliszyn, E., Styer, P. E. Evaluation of the extent of nonlinearity in reportable range studies. Arch. Pathol. Lab. Med., 2000, 124, 9, 1331–1338.

4. Reed, A. H., Henry, R. J., Mason, W. B. Influence of statistical method used on the resulting estimate of normal range. Clin. Chem., 1971, 17, 4, 275-284.

5. Harrell, F. E., Davis, C. E. A new distribution-free quantile estimator. Biometrika, 1982, 69, 3, 635-640.

6. Apple, F. S., Sandoval, Y., Jaffe, A. S., Ordonez-Llanos, J. Cardiac troponin assays: Guide to understan-ding analytical characteristics and their impact on clinical care. Clin Chem., 2017, 63, 1, 73–81.

7. Herman, D. S., Kavsak, P. A., Greene, D. N. Variability and Error in Cardiac Troponin Testing: An ACLPS Critical Review. Am. J Clin. Pathol., 2017, 148, 4, 281–295.

8. Koerbin, G. L. High sensitivity troponin - its use in diagnosis of cardiac dysfunction. Thesis, University of Canberra, Australia. Dostupné z http://www.canberra.edu.au/researchrepository/file/76337dee-aa98-4d33-91ad-34319e1826cd/1/full_text.pdf (Přístup 25.1.2019).

9. Wu, A. H. B., Christenson, R. H., Greene, D. N. 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, 4, 645-655.

10. Apple, F. S., Jaffe, A. S., Collinson, P. et al. International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin. Biochem., 2015, 48, 4-5, 201-3.

11. Eggers, K. M., Apple, F. S., Lind, L., Lindahl, B. The applied statistical approach highly influences the 99^th percentile of cardiac troponin I. Clin. Biochem., 2016, 49, 15, 1109-1112.

12. R Development Core Team (2004). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org (Přístup 26.3.2019).

13. Nyblom, J. Statistics & Probability Letters, 1992, 14, 2, 129-131.

14. Iglewicz, B., Hoaglin, D. How to detect and handle outliers. Milwaukee (WI): ASQC Quality Press, 1993, ISBN 087389247X.

15. Tukey, J. W. Exploratory data analysis. Reading. Massachusetts: Addison-Wesley, 1997, 712 s. ISBN 0201076160.

16. Hoaglin, D. C. John W. Tukey and Data Analysis. Sta-tist. Sci., 2003, 18, 3, 311-318.

17. Cullen, L. A., Mills, N. L. Point: The Use of Sex-Specific Cutpoints for High-Sensitivity Cardiac Troponin Assays. Clin. Chem., 2017, 63, 1, 261-263.

18. Giannitsis, E. Counterpoint: Potential concerns regarding the use of sex-specific cutpoints for high-sensitivity troponin assays. Clin. Chem., 2017, 63, 1, 264-266.

19. Collinson, P., Heung, Y. M., Gate, D. Influence of Population Selection on the 99^th Percentile Reference Value for Cardiac Troponin Assays. Clin. Chem., 2015, 58, 1, 219-225.

20. Theodorsson, E. Limit of detection, limit of quantification and limit of blank. Dostupné z https://www.eflm.eu/files/efcc/Zagreb-Theodorsson_2.pdf (Přístup 25.1.2019).

21. Magnusson, B., Örnemark, U. (eds.). Eurachem Guide: The Fitness for Purpose of Analytical Methods – A Laboratory Guide to Method Validation and Related Topics, (2^nd ed. 2014). ISBN 978-91-87461-59-0 Dostupné z https://www.eurachem.org/images/stories/Guides/pdf/MV_guide_2nd_ed_EN.pdf (Přístup 25.1.2019).