A critical appraisal of experimental factors influencing the definition of the 99th percentile limit for cardiac troponins

Abstract

The recently released document by the Global Task Force on the "universal" definition of myocardial infarction (MI) recommends a single decision limit for cardiac troponin (cTn) corresponding to the 99th percentile limit of the reference value distribution [99th upper reference limit (URL)] for the diagnosis of patients presenting with suspected MI. However, use of this cut-off concentration posed a problem because most assays do not have the sensitivity to consistently measure cTn in the blood of apparently healthy individuals, with a high proportion of the values being below the method's detection limit. In addition to the influence of assay sensitivity, the 99th URL for cTn can vary depending on the reference population used, and its sample size. A marked difference can also be observed between the 99th URL obtained using plasma vs. that obtained with serum. Finally, some interferences with cTn measurement (e.g., by heterophile antibodies) may become more noticeable using assays that have increased analytical sensitivity that measure lower concentrations of these markers. In conclusion, a number of issues can markedly influence the definition of the 99th URL for cTn, which most clinicians are unaware of and may markedly condition the clinical performance of the test in routine practice.