Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in a Population-Based Sample of US Children and Adolescents

Abstract

BACKGROUND: Myocardial injury is an important pediatric diagnosis. Establishing normative data from a representative pediatric sample is vital to provide accurate upper reference limits (URLs) for defining myocardial injury using high-sensitivity cardiac troponin. METHODS: Among participants 1 to 18 years of age in the 1999–2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using one assay (Roche) and high-sensitivity troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy subgroup, we estimated 97.5th and 99th percentile URLs for each assay using the recommended nonparametric method. RESULTS: Of 5695 pediatric participants, 4029 met criteria for the healthy subgroup (50% males; mean age 12.6 years). Our 99th percentile URL estimates for all 4 high-sensitivity troponin assays among children and adolescents were lower than the manufacturer-reported URLs (derived from adults). The 99th percentile URLs (95% CI) were 15 ng/L (95% CI, 12–17) for high-sensitivity troponin T, 16 ng/L (95% CI, 12–19) for high-sensitivity troponin I with the Abbott assay, 38 ng/L (95% CI, 25–46) for high-sensitivity troponin I with the Siemens assay, and 7 ng/L (95% CI, 5, 12) for high-sensitivity troponin I with the Ortho assay. The 95% CIs for age-, sex-, and race-specific 99th percentile URLs overlapped. However, the 97.5th percentile URL for each assay was measured with superior statistical precision (ie, tighter 95% CIs) and demonstrated differences by sex. For male compared with female children, 97.5th percentile URLs were 11 ng/L (95% CI, 10–12) versus 6 ng/L (95% CI, 6–7) for high-sensitivity troponin T, 9 ng/L (95% CI, 7–10) versus 5 ng/L (95% CI, 4–6) for high-sensitivity troponin I with the Abbott assay, 21 ng/L (95% CI, 18–25) versus 11 ng/L (95% CI, 9–13) for high-sensitivity troponin I with the Siemens assay, and 4 ng/L (95% CI, 3–5) versus 2 ng/L (95% CI, 1–3) for high-sensitivity troponin I with the Ortho assay. In contrast to the 99th percentiles, the point estimates of 97.5th percentile pediatric URLs for cardiac troponin were also much more stable to differences in the analytic approaches taken to estimate URLs. CONCLUSIONS: Because myocardial infarction is rare in adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile URLs might be considered to define pediatric myocardial injury.

Cardiac Troponin Reporting in Children and Young Adults: Time to Change Clinical Practice

“…Whereas this was not a systematic study, it was performed in children not known to have cardiac disease, and the authors observed that 60% of children with elevated cardiac troponin values had a cardiac diagnosis, compared with 12% in those tested without an elevated cardiac troponin level. 14 The findings reported by McEvoy et al 11 are intuitive and consistent with previous studies in adult populations, but there are limitations to the work. The use of stored rather than fresh samples creates some uncertainty, and data on the stability of cardiac troponin after long-term storage are needed.…”

“…In this issue, McEvoy et al 11 report findings from the National Health and Nutrition Examination Survey (NHANES), in which cardiac troponin levels were measured in 5695 healthy children and young adults from the United States between 1 and 18 years of age with 4 high-sensitivity assays used widely in clinical practice. They report several important findings that increase our understanding of cardiac troponin levels in this setting and challenge current practice and guideline recommendations.…”

“…McEvoy et al 11 challenge the current consensus on defining the upper reference limit of cardiac troponin using the 99th percentile, suggesting that the 97.5th percentile would be more appropriate for children and young adults. They provide both methodological and clinical arguments for this suggestion.…”

“…Until long-term follow-up data are available, the interpretation of a borderline elevation in cardiac troponin concentra-tion in children should be done with considerable caution. Greater precision around the estimates of the 97.5th percentile enabled McEvoy et al 11 to demonstrate that both cardiac troponin I and T concentrations differed significantly by sex in children and young adults. This observation is consistent in adult populations 7,12 and in a previous study of healthy children using cardiac troponin T. 13 Observed differences were more pronounced in adolescence, indicating that sex differences may be related to physiological changes during puberty.…”

Quantitative Detection of Multiple Cardiovascular Biomarkers by an Antibody Microarray-Based Metal-Enhanced Fluorescence Assay

“…Under optimal conditions, various concentrations of cardiovascular biomarkers in the reaction buffer and 10% plasma were added to the antibody microarray to explore the practicality of this method. The AMMEFA displays a broad detection range from pg mL –1 to μg mL –1 , which is suitable for both low (e.g., cTnI and copeptin in healthy people are 16 pg mL –1 and 70 pg mL –1 , respectively) , and high (e.g., CRP in ACS patients is 19 μg mL –1 ) abundance cardiovascular biomarkers detection. The values of (F/F 0 – 1) are linearly related to the logarithm of antigens concentrations (Figure a–g), and the LODs can be as low as 0.3 pg mL –1 for NT-proBNP, 65.7 pg mL –1 for CRP, 0.2 pg mL –1 for H-FABP, 8.3 pg mL –1 for D-Dimer, 0.2 pg mL –1 for myoglobin, 0.07 pg mL –1 for cTnI, and 0.6 pg mL –1 for copeptin (Table ).…”