Establishing Reference Values in Healthy Participants for the Cardiac Troponin T High-Sensitivity Gen 6 Assay: REF-TSIX Global Reference Study
Lori B Daniels, Christian Mueller, Evangelos Giannitsis, Steven J. R. Meex, David Buehlmann, Peter Dilba, Garnet Bendig, Mette Cole, Richard Body, Robert H Christenson, Christa M. Cobbaert, Christopher R deFilippi, Kai M. Eggers, Kenji Inoue, A S Jaffe, Cian P. McCarthy, J. McCord, Johannes T Neumann, T. Omland, Cynthia Papendick, Yader Sandoval, Jack Wei Chieh Tan, Martin Than, Raphael Twerenbold, W Frank Peacock, Nicholas L Mills, the TSIX investigators, Michael B. Jacobs, Gregg Lucksinger, Richard Powell, Daniel Johnson, Hugh Coleman, M Fein, Joseph Surber, Jack B. Vu, Michael Hassman, John Hernandez, Judith Kirstein, Christian Tomaszewski, Michael S. Runyon, Jonathan Gong, D. Wein, Sara Andrabi, David Kopin, Germain Larrain, Naheem Tahirkheli, Brian Clemency, Shuaib Abdullah, Ravi S. Hira, H A Klausner, Simon A. Mahler, Chad Crystal, Gary Headden, Simon A. Mahler, Gary Headden, Peter Chaille, Chad Aaron Cannon, Alexander Limkakeng, Vaishal Tolia, Barry J. Knapp, Mohammad Massoomi, Yader Sandoval, Alexander Limkakeng, Emily Ko, Brian Clemency, Verónica Luzzi, Robert Christenson, Nam K. Tran, Jennifer Powers Carson, Jan Niederdöckl, F Cacioppo, E. Kolev, T. Popov, Andrey Petrov, Dobri Hazarbasanov, lana Simova, Luci Suganthi Magimaiseelan, Christine Kosch, G Klein, Kai Mehltretter, Joachim Sauter, Sybille Baumann, Martin Moeckel, Raphael Twerenbold, Matthias Muller-Hennessen, Moritz Biener, P. Findeisen, Volkher Scharnhorst, Torbjøm Omland, Urszula Wilczek-Kosowska, Ewa Zimmer-Satora, Ewa Krecipro-Nizińska, O Miró, Víctor Jiménez Díaz, C Mueller, Michael Christ, Stephen Lynch, R. A. F. BODY, Shunji Matsuki, Takashi Eto
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.