Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in U.S. Adults
Key result
Healthy adult hs-cTnI 99th percentile cutoffs fall substantially below manufacturer reference limits, varying by age and sex.
- n=12,545
Why the study?
To estimate high-sensitivity troponin 99th percentile upper reference limits that are representative of the US adult population, overall and by sex, race/ethnicity, and age group.
Key Points
- To estimate 99th percentile upper reference limits for four high-sensitivity troponin assays representative of the general US adult population across sex, race/ethnicity, and age groups.
- Evaluated 12,545 adult participants from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) to identify a strictly defined healthy reference subgroup of 2,746 adults.
- Measured hs-troponin-T using one assay (Roche) and hs-troponin-I using three assays (Abbott, Siemens, and Ortho), calculating 99th percentile upper reference limits (URLs) with non-parametric methods.
- The 99th percentile URL for Roche hs-troponin-T was 19 ng/L (matching manufacturer: 19 ng/L), whereas hs-troponin-I URLs were lower than manufacturer specifications: 13 ng/L (95% CI 10, 15) for Abbott (manufacturer: 28 ng/L), 5 ng/L (95% CI 4, 7) for Ortho (manufacturer: 11 ng/L), and 37 ng/L (95% CI 27, 66) for Siemens (manufacturer: 46.5 ng/L).
- Assay URLs were significantly higher in males than females (all p<0.05) and significantly lower in adults aged <40 years compared to ≥60 years (all p<0.001 by rank sum testing), while no differences were observed by race/ethnicity.
Study Design
Type
Cross-Sectional (n=12,545)
Structured PICO
P
Population
12,545 US adults from NHANES, including a strictly defined healthy reference subgroup of 2,746 participants (mean age 37.4, 50% female) used to estimate 99th percentile upper reference limits for high-sensitivity troponin assays.
E
Exposure
Measurement of high-sensitivity troponin T (Roche) and I (Abbott, Siemens, Ortho) in stored serum samples
C
Comparator
Manufacturer-reported 99th percentile upper reference limits
O
Outcome
99th percentile upper reference limit (URL) for each high-sensitivity troponin assaysurrogate
Current manufacturer-reported 99th percentile URLs for hs-troponin I may be too high, and age- and sex-specific thresholds should be considered to accurately define myocardial injury.
Limitations
- Only studied four hs-troponin assays
- hs-troponin concentrations were obtained from stored frozen samples
- Measurements were conducted in serum and may not be directly applicable to plasma
- Age categories were chosen for consistency with guidelines rather than as a continuous variable
- Did not have access to electrocardiogram or echocardiogram data
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“What I believe our data have clarified and now [should] motivate a serious conversation about is the use of age-specific cut points for high-sensitivity troponin in the diagnosis of myocardial injury.”
Implication
Manufacturer hs-troponin URLs may overestimate myocardial injury thresholds; challenges current cutoffs and leaves open prospective validation of age- and sex-specific values.
Abstract
Background: Myocardial injury is defined as a cardiac troponin above the sex-specific 99th percentile (upper reference limit, URL) of a healthy reference population. Objectives: To estimate high-sensitivity (hs) troponin URLs that are representative of the US adult population; overall and by sex, race/ethnicity, and age group. Methods: Among adults participating in the 1999–2004 National Health and Nutrition Examination Survey (NHANES), we measured hs-troponin-T using one assay (Roche) and hs-troponin-I using three assays (Abbott, Siemens, and Ortho). In a strictly defined healthy reference subgroup, we estimated 99th percentile URLs for each assay using the recommended non-parametric method. Results: Of 12,545 participants, 2,746 met criteria for the healthy subgroup (mean age 37 years, 50% male). The NHANES 99th percentile URL for hs-troponin-T (19 ng/L) matched the manufacturer-reported URL (19 ng/L). NHANES URLs were 13 ng/L (95% CI 10, 15) for Abbott hs-troponin-I (manufacturer: 28 ng/L), 5 ng/L (95% CI 4, 7) for Ortho hs-troponin-I (manufacturer: 11 ng/L), and 37 ng/L (95% CI 27, 66) for Siemens hs-troponin-I (manufacturer: 46.5 ng/L). There were significant differences in URLs by sex, but none by race/ethnicity. Furthermore, the 99th percentile URLs for all four hs-troponin assays were statistically significantly lower in healthy adults aged <40 years compared to ≥60 years (all p<0.001 by rank sum testing). Conclusions: We found URLs for hs-troponin-I assays that were substantially lower than currently listed 99th percentile URLs. There were significant differences in hs-troponin-T and hs-troponin-I URLs by sex and by age group in healthy US adults but none by race/ethnicity.
Discussion
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Cite This Study
McEvoy et al. (2023) conducted a cross-sectional in Healthy US adults (reference population for myocardial injury) (n=12,545). High-sensitivity troponin assays (Roche, Abbott, Siemens, Ortho) vs. Manufacturer-reported 99th percentile URLs was evaluated on 99th percentile upper reference limit (URL) for high-sensitivity troponin assays. The 99th percentile URLs for hs-troponin-I assays in healthy US adults were substantially lower than manufacturer-reported URLs, with significant differences by sex and age but not race/ethnicity.