What Constitutes a Relevant Change in High-Sensitivity Troponin Values over Serial Measurement?

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The universal definition of myocardial infarction (MI)2 requires both an increase in cardiac troponin concentrations and a rise and/or fall in values over serial measurement (1). It is noteworthy that there is no mention in the current consensus document regarding what magnitude of change in troponin values should be required to meet the definition for spontaneous MI. The conspicuous absence of criteria to define troponin concentration change in that document reflects important knowledge gaps and the lack of consensus with regard to this important component of the MI definition. The introduction of high-sensitivity troponin assays has created both challenges and opportunities with regard to the universal MI definition. A major challenge is the observation that a substantial proportion of individuals without MI have troponin concentrations persistently above the MI detection limit (2). This is in part related to the effects of age, male sex, subclinical cardiac structural abnormalities, and renal disease on troponin concentration (3), but is also influenced by poor characterization of the 99th percentile threshold, particularly for the high-sensitivity cardiac troponin T (hs-cTnT) assay. Indeed, a recent study that included data from 3 large population-based cohorts has shown that the recommended 14-ng/L threshold value for defining MI by use of the hs-cTnT assay is actually well below the actual 99th percentile value for men ≥50 years and women ≥65 years old (4). On the other hand, higher precision of the high-sensitivity troponin assays should improve characterization of troponin concentration changes over serial measurement. Indeed, it has been argued strongly that assessment of serial high-sensitivity troponin changes is the solution to the “specificity problem” with these assays (1, 5); however, little guidance is available as to what constitutes a relevant change. In the past few years, data have begun to emerge from 2 broad categories of studies …