Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays
Gus Koerbin1, Walter P Abhayaratna, Julia M Potter
1ACT Pathology, Garran, ACT 2605, Australia; University of Canberra, ACT 2601, Australia.
Insights
Determining accurate 99th percentile values for cardiac troponin I and T requires objective laboratory and clinical assessments, not just self-reported health. Excluding subjects with subclinical disease significantly lowers these crucial cardiac biomarker reference ranges.
Area of Science:
- Cardiology
- Biomarker Research
- Clinical Diagnostics
Background:
- Establishing accurate reference ranges for cardiac biomarkers is critical for diagnosing myocardial injury.
- Current 99th percentile values for cardiac troponin may not adequately reflect a truly healthy population.
Purpose of the Study:
- To determine precise 99th percentile values for cardiac troponin I (cTnI) and cardiac troponin T (cTnT) using objective criteria.
- To evaluate the impact of excluding individuals with subclinical disease on these reference values.
Main Methods:
- Measured cTnI and cTnT using high-sensitivity assays in a large cohort of apparently healthy individuals.
- Excluded subjects with potential subclinical disease using objective laboratory (e.g., eGFR, NT-proBNP) and clinical (history, examination, echocardiogram) criteria.
- Calculated 99th percentiles stratified by sex and age.
Main Results:
- Over 50% of subjects were excluded based on objective criteria, with higher exclusion rates in older individuals.
- The 99th percentile for cTnI in men aged <75 years decreased by over 50% (from 22.9 ng/L to 10.3 ng/L).
- Significant reductions in 99th percentiles were also observed for other age groups and for cTnT.
Conclusions:
- Self-reported health status is insufficient for establishing accurate cardiac troponin 99th percentiles.
- Objective laboratory measures, clinical assessments, and echocardiography are essential for defining a healthy population for biomarker reference ranges.
- These findings highlight the need for revised reference standards, particularly for older individuals.
Objective:
Using objective laboratory and clinical criteria to more accurately determine the 99th percentile values for cardiac troponin I and T.
Design And Methods:
We measured cardiac troponin T and cardiac troponin I with high-sensitivity assays in a large cohort of apparently healthy community subjects and calculated 99th percentiles for different sexes and ages. Subjects with possible subclinical disease were eliminated based on objective laboratory criteria, eGFR and NT-proBNP, and clinical criteria, history and examination and echocardiogram.
Results:
For men and women of all ages, separately, more than 50% of subjects were excluded using these criteria, with a lesser proportion of younger subjects being excluded. In men aged <75 years, the 99th percentile for cTnI decreased by more than 50% from 22.9 ng/L to 10.3 ng/L. In other age groups and for cTnT the decrease was smaller (%) but still considerable.
Conclusions:
For establishing cardiac troponin 99th percentiles, simply using self-reporting of health is insufficient. Objective laboratory measures and clinical and echocardiographic assessments are essential to define a healthy population, especially in older persons.
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