Myocardial Injury Limits for Troponin Assays

Quick Takes

  • This study aimed to determine 99th percentile upper reference limits (URLs) for four hs-troponin assays using a healthy reference subsample of the general US adult population, examining variations by age, sex, and race/ethnicity, utilizing data from NHANES.
  • High-sensitivity troponin I 99th percentile URLs were lower than manufacturer-reported values. In contrast, hs-troponin T 99th percentile URLs matched those reported by manufacturers, with significant differences observed by age and sex but not by race/ethnicity.

Study Questions:

What are the 99th percentile upper reference limits (URLs) for four high-sensitivity troponin (hs-troponin) assays in a healthy reference subsample of the general US adult population, and how do these values differ by age, sex, and race/ethnicity?


This study used data and blood samples from the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. Hs-troponin was measured in 12,545 nonpregnant participants aged ≥18 years, taken between 1999 and 2004, using four hs-troponin assays, including three hs-troponin I assays (Siemens, Abbott, Ortho) and one hs-troponin T assay (Roche). A healthy reference sample of 2,746 participants was selected based on various criteria, including the absence of cardiovascular disease, body mass index within the range of 18.5-30 kg/m2, and no use of cardiac medications. The analysis aimed to estimate the hs-troponin 99th percentiles for each assay in 2,746 healthy individuals and were validated in 10,704 adults without known coronary or kidney disease.


The study found that the 99th percentile URL for the Roche hs-troponin T assay matched the manufacturer-reported URL. In contrast, the 99th percentile URLs for the three hs-troponin I assays were lower in the sample than those reported by the manufacturers. There were significant differences in the 99th percentile URLs for all four hs-troponin assays according to sex, with higher values for males than females. Differences were also observed between the youngest and oldest age categories for hs-troponin T and the hs-troponin I (Ortho) assays, but not according to race/ethnicity. In the general US adult population without cardiovascular or chronic kidney disease (n = 10,704), the nationally representative 99th percentiles for hs-troponin were higher than those calculated in the healthy reference sample, with significant differences across sex and age groups.


The 99th percentile URLs for hs-troponin I in the healthy reference population were lower than manufacturer-reported URLs, while the hs-troponin T 99th percentile URLs were similar, with both sex and age playing significant roles in determining these values.


One interesting aspect of the study is that the 99th percentile URLs for hs-troponin I assays in the healthy subsample were lower than the manufacturer-reported URLs, while the 99th percentile URLs for hs-troponin T assays matched those reported by manufacturers. This suggests that the cohorts previously used by manufacturers to derive 99th percentile URLs may not have fully excluded people with underlying health conditions.

The presence of significant differences in hs-troponin 99th percentile URLs according to sex and age, but not race/ethnicity, supports the recommendation of using sex-specific hs-troponin URLs in defining myocardial injury, as suggested in the 4th Universal Definition of Myocardial Infarction. However, the study also highlights the potential value of considering age-specific URLs, which could have significant implications for diagnosing myocardial injury and, consequently, myocardial infarction.

The study’s findings on sex- and age-specific URLs could lead to significant changes in clinical practice. For instance, using these URLs might reduce the number of older adults meeting criteria for myocardial injury, as they tend to have higher hs-troponin values. This could, in turn, decrease unnecessary work-ups for myocardial infarction in the absence of compelling symptoms. However, it is important to note that the study focused solely on defining myocardial injury, and further research is needed to assess the impact of employing both sex- and age-specific hs-troponin thresholds for diagnosing myocardial infarction in clinical cohorts.

Clinical Topics: Acute Coronary Syndromes, Geriatric Cardiology, Prevention, ACS and Cardiac Biomarkers

Keywords: Acute Coronary Syndrome, Aged, Biomarkers, Body Mass Index, Ethnic Groups, Heart Injuries, Myocardial Infarction, Primary Prevention, Renal Insufficiency, Chronic, Sex Characteristics, Troponin I, Troponin T

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