Manufacturer's Troponin Reference Values Don't Apply to Kids

by Nicole Lou, Senior Staff Writer, MedPage Today April 21, 2023

New upper reference limits (URLs) for troponin assays were introduced for pediatric medicine, the goal being greater accuracy in defining myocardial injury in children.

From a reference group of healthy children and adolescents sampled from the general U.S. population, researchers determined the 97.5th and 99th percentile URLs for four high-sensitivity cardiac troponin (hs-cTn) assays. The 97.5th percentile values specifically were favored for their superior statistical precision and differentiation by sex, according to researchers led by John McEvoy, MB BCh, MHS, PhD, of University of Galway and National Institute for Prevention and Cardiovascular Health in Ireland.

Published in Circulation, their study reported the 97.5th percentile thresholds for myocardial injury between boys and girls:

Like the 97.5th percentile URLs, the calculated 99th percentile values for children were similarly lower than the manufacturer-reported URLs derived from adults. However, they were less precise, did not separately clean by age and sex, and were less stable to differences in the analytic approaches to percentile estimation and outlier removal, McEvoy's group said.

In adults, the assay manufacturer-determined 99th percentile URL is the typical troponin cutoff for myocardial injury suggestive of myocardial infarction (MI). Between men and women, the listed sex-specific values are:

Without formal guidance on the use of hs-cTn in pediatrics, the concept of the 99th percentile cutoff has been applied to children even though troponin is applied differently in these patients.

"In the relatively uncommon instances that cardiac troponin is measured in pediatric care, it typically is used to investigate suspected pathogeneses of myocardial injury, including, for example, myocarditis arising from SARS-CoV-2 infection or novel cancer therapies," according to the study authors.

"Given that MI is rare in children and adolescents, our results support the use of more stable and statistically precise sex-specific 97.5th percentile URLs in the assessment of pediatric myocardial injury," the authors said, adding that 97.5th percentile URLs are already commonplace in flagging abnormalities in other lab values in pediatrics.

McEvoy and colleagues nevertheless said they published the 99th percentile URLs alongside the 97.5th percentile values so that local clinical laboratories can choose which measure to use in determining myocardial injury among their pediatric population."

To derive these URLs, the investigators relied on frozen serum samples from over 4,000 pediatric participants of the 1999-2004 National Health and Nutrition Examination Survey.

Results may therefore not be applicable to measurements obtained in fresh plasma, they acknowledged.

The Ortho hs-cTnI assay is not available for clinical use in the U.S.

Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded by a grant from the Foundation for the National Institutes of Health Biomarkers Consortium, supported by Abbott Laboratories, AstraZeneca, Johnson & Johnson, the National Dairy Council, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics.

McEvoy had no disclosures; a study co-author reported grant support from Roche Diagnostics, Fujirebio Diagnostics, Beckman Coulter, Siemens Healthcare Diagnostics, Ortho Clinical Diagnostics, Becton Dickinson, Abbott Diagnostics, Mitsubishi, and Horiba Medical; and consulting agreements with PixCell, Beckman Coulter, Quidel, Siemens Healthineers, and Roche Diagnostics.

Primary Source

Circulation

Source Reference: McEvoy JW, et al "Myocardial injury thresholds for 4 high-sensitivity troponin assays in a population-based sample of US children and adolescents" Circulation 2023; DOI: 10.1161/CIRCULATIONAHA.122.063281.