Mahler, Simon A.

Abstract Background Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance guidelines for the evaluation and diagnosis of acute chest pain make important recommendations that include the recognition of high-sensitivity cardiac troponin (hs-cTn) as the preferred biomarker, endorsement of 99th percentile upper reference limits to define myocardial injury, and the use of clinical decision pathways, as well as acknowledgment of the uniqueness of women and other patient subsets. Details on how to integrate hs-cTn into clinical practice are less extensively addressed. Clinicians should be aware of some of the analytical aspects related to hs-cTn assays regarding the limit of detection and the limit of quantitation and how they are used clinically, especially for the single sample strategy to rule out acute myocardial infarction. Likewise, it is important for clinicians to understand issues related to the derivation of the 99th percentile upper reference limit; the value of sex-specific 99th percentile upper reference limits; how to use changing concentrations (deltas) to facilitate diagnosis and risk stratification of patients with suspected acute coronary syndrome, including the differentiation of acute from chronic myocardial injury; and how to best integrate the use of hs-cTn with clinical decision pathways. With the use of hs-cTn, conditions such as type 2 myocardial infarction become more common, whereas others such as unstable angina become less frequent but still occur. Sections relating to these issues are included.