The applied statistical approach highly influences the 99th percentile of cardiac troponin I

Kai M. Eggers, Fred S. Apple, Lars Lind, Bertil Lindahl

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background Cardiac troponin (cTn) is the biomarker of choice for assessment of patients with acute coronary syndromes. Guidelines recommend the cTn 99th percentile derived from a cardiovascular healthy reference population as decision threshold. The importance of standardized criteria for the composition of such a reference population is well acknowledged. In this analysis, we investigated to which extent different statistical methods might have bearing on the calculated cTnI 99th percentile. Methods cTnI (Abbott) 99th percentiles were determined in 521 cardiovascular healthy community-dwelling subjects using the nonparametric method, the Harrell-Davis bootstrap method and the robust method together with different tests to identify potential outliers (Dixon, Tukey, Reed) and different statistical softwares. Results The cTnI 99th percentiles (nonparametric method) were 37 ng/L (total population), 42 ng/L (men) and 25 ng/L (women). These estimates differed by − 7.4% to + 5.7% using the Harrell-Davis bootstrap method and were up to 64.1% lower using the robust method. For the robust method, cTnI 99th percentiles varied by 44.2% depending on the applied software. The method of Tukey classified nine subjects as outliers while no outlier was detected using the other methods. Excluding these nine subjects resulted in up to 60.2% lower cTnI 99th percentiles. Conclusions Our results emphasize the need of a standardized statistical approach to calculate cTnI 99th percentiles. Our findings support the use of the nonparametric method and a conservative approach to detect outliers. This requires that the assessed population is sufficiently large and well selected on the basis of stringently applied clinical criteria.

Original languageEnglish (US)
Pages (from-to)1109-1112
Number of pages4
JournalClinical Biochemistry
Issue number15
StatePublished - Oct 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
The PIVUS study has received funding from grants from the Swedish Heart-Lung Foundation (grant no. 20100947 ), and the Swedish Society of Medicine (grant nos. SLS-248691 and SLS-407281 ). Economic support for the reagents to analyze cTnI was provided by Abbott. These organizations had no role in the conduction, analysis and interpretation of the present data, the writing of this report and the decision to publish.

Publisher Copyright:
© 2016 The Canadian Society of Clinical Chemists


  • 99th percentile
  • Cardiac troponin
  • Statistics
  • Upper reference level


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