A comprehensive review of upper reference limits reported for (high-)sensitivity cardiac troponin assays: the
Eline P M Cardinaels1, Alma M A Mingels, Leo H J Jacobs
1Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
Insights
Establishing accurate cardiac troponin (cTn) cut-off values for acute myocardial infarction (AMI) diagnosis is challenging. Current reference limits vary, and populations used to determine them often lack rigor, necessitating improved standardization for reliable AMI detection.
Area of Science:
- Clinical Chemistry
- Cardiovascular Diagnostics
- Biomarker Assay Evaluation
Background:
- Cardiac troponins (cTn) are crucial biomarkers for diagnosing acute myocardial infarction (AMI).
- Current guidelines recommend using the 99th percentile upper reference concentration from a healthy population for AMI diagnosis.
- Significant variability exists in the upper reference limits (URL) employed across different assays, complicating AMI diagnosis.
Purpose of the Study:
- To provide an overview of the analytical performance and upper reference limits of seven high-sensitivity cTn assays.
- To assist laboratory specialists in defining appropriate diagnostic cut-off values for AMI.
- To highlight discrepancies between current practices and guideline recommendations for cTn assay validation.
Main Methods:
- Review of analytical performance and upper reference limits for seven contemporary high-sensitivity cTn assays.
- Evaluation of reference population characteristics, including sample size and inclusion criteria, from published studies.
- Comparison of observed 99th percentile upper reference limits with guideline recommendations.
Main Results:
- None of the evaluated reference populations fully adhered to guideline recommendations.
- A significant proportion of studies (40%) failed to meet the minimum subject requirement of 300 individuals.
- Fifty percent of studies lacked reported inclusion criteria, and more stringent criteria correlated with lower 99th percentile limits.
- Higher troponin cut-offs were observed in men and elderly individuals, suggesting potential need for sex- and age-specific cut-offs.
Conclusions:
- Existing reference populations for cTn assays often do not meet recommended standards for AMI diagnosis.
- Variability in assay performance and reference population selection complicates the establishment of universal cTn cut-off values.
- There is a critical need for large, rigorously screened reference populations to establish accurate and reliable cTn upper reference limits for improved AMI diagnosis.
Abstract:
Cardiac troponins (cTn) are the preferred markers for the diagnosis of acute myocardial infarction (AMI). The guidelines recommend the use of the 99th percentile upper reference concentration of a healthy population as the diagnostic cut-off for AMI. However, a broad range of upper reference limits is still employed, complicating the diagnosis of AMI. This overview is meant to assist laboratory specialists to define an appropriate cut-off value for the diagnosis of AMI. Therefore, we provide an overview of the analytical performance and upper reference limits of seven (high-)sensitivity cTn assays: Roche high-sensitivity cTnT and ADVIA Centaur, Stratus CS, Dimension Vista, Vitros ECi, Access and Architect cTnI assays. It is shown that none of the reference populations completely met the guidelines, including those in package inserts. Forty percent of the studies collected less than the advised minimum of 300 subjects. Many studies (50%) did not report their inclusion criteria, while lower 99th percentile limits were observed when more stringent selection criteria were applied. Higher troponin cut-offs were found in men and elderly subjects, suggesting sex- and age-specific cut-offs would be considered. Therefore, there is still need for a large, rigorously screened reference population to more accurately establish cTn upper reference limits.
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