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Establishing Reference Values in Healthy Participants for the Cardiac Troponin T High-Sensitivity Gen 6 Assay: REF-TSIX Global Reference Study

  • the TSIX investigators
  • University of California at San Diego
  • University of Basel
  • Heidelberg University 
  • Maastricht University
  • Roche Diagnostics International AG
  • Roche Diagnostics GmbH
  • Roche Molecular Systems
  • Manchester University NHS Foundation Trust
  • University of Manchester
  • University of Maryland, Baltimore
  • Leiden University
  • Uppsala University
  • Tokyo Heart Rhythm Clinic Shinjuku
  • Juntendo University
  • Mayo Clinic Rochester, MN
  • Harvard University
  • Henry Ford Health System
  • University of Hamburg
  • Partner Site Hamburg/Kiel/Lübeck
  • Monash University
  • University of Oslo
  • Royal Adelaide Hospital
  • Adelaide University
  • Allina Health
  • National Heart Centre Singapore
  • Duke-NUS Medical School
  • Singapore Health Services
  • Canterbury District Health Board
  • University of Otago
  • University of Kansas
  • Baylor College of Medicine
  • University of Edinburgh

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods: Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results: The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions: This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

Original languageEnglish
Pages (from-to)488-502
Number of pages15
JournalClinical Chemistry
Volume72
Issue number4
DOIs
StatePublished - Apr 2026

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