Accessible Requires Authentication Published by De Gruyter May 24, 2021

Determination of sex-specific 99th percentile upper reference limits for a point of care high sensitivity cardiac troponin I assay

Fred S. Apple, Karen Schulz, Christian W. Schmidt ORCID logo, Trees S. Y. van Domburg, Judith M. Fonville and Femke K. de Theije

Abstract

Objectives

High sensitivity (hs) cardiac troponin (cTn) assays are defined per the IFCC Committee on Clinical Application of Cardiac Biomarker (C-CB) by the ability to measure ≥ 50% of concentrations greater than the limit of detection (LoD) with an impression of ≤10% at sex-specific 99th percentiles. Our study determined the sex-specific 99th percentile upper reference limits for males and females utilizing heparinized plasma from AACC universal sample bank for the Siemens point of care (POC) Atellica® VTLi hs-cTnI immunoassay.

Methods

Apparently healthy subjects, included overall 693, males 363, and females 330, following exclusionary surrogate biomarker use of hemoglobin A1c, NT-proBNP, and eGFR, along with statin medication. hs-cTnI was measured in a central laboratory, on multiple POC Atellica® VTLi immunoassay analyzers. The LoD was 1.24 ng/L and the 10%CV concentration was 6.7 ng/L. 99th percentile URLs were determined by the nonparametric (NP) method.

Results

Histograms of the hs-cTnI concentrations (ng/L) for males and females were used to visualize the distributions and concentrations in men and women and differed significantly (pre- and post-exclusion, both p <0.001). 99th percentile URLs were: overall 23 ng/L (90% CI 20–32 ng/L); male 27 ng/L (CI 21–37 ng/L); female 18 ng/L (CI 9–78 ng/L). The percentages of subjects having a measurable concentration ≥ the LoD were: overall 83.7%, male 87.3%, female 79.7%.

Conclusions

Our findings show the novel POC Atellica® VTLi hs-cTnI assay meets the designation of a ‘high-sensitivity’ assay using heparinized plasma.


Corresponding author: Fred S. Apple, PhD, Department of Laboratory Medicine and Pathology, Hennepin Healthcare/HCMC, Minneapolis, MN, USA; Hennepin Healthcare Research Institute/Hennepin County Medical Center, Clinical Laboratories P4, 701 Park Avenue, Minneapolis, MN 55415, USA; and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA, Phone: +612 873 3324, Fax: +612 904 4229, E-mail:

Funding source: Hennepin Healthcare Research Institute

Award Identifier / Grant number: Funded in part

Funding source: Siemens Healthineers

  1. Research funding: This study was funded in part by Siemens Healthineers.

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

  3. Competing interests: FSA: Board of Directors, HyTest Ltd.; Honorarium Advisory Boards: Siemens Healthcare, Instrumentation Laboratory, Qorvo; Research PI through Hennepin Healthcare Research Institute (not salaried): Abbott Diagnostics, Abbott Point of Care, Roche Diagnostics, Siemens Healthcare, Quidel/Alere, Ortho-Clinical Diagnostics, Beckman Coulter; Other: Associate Editor Clinical Chemistry.

  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.

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Received: 2021-03-01
Accepted: 2021-05-14
Published Online: 2021-05-24
Published in Print: 2021-08-26

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