Letter by Gibson and McEvoy Regarding Article, “Influence of Age on the Diagnosis of Myocardial Infarction”

HomeCirculationVol. 147, No. 17Letter by Gibson and McEvoy Regarding Article, “Influence of Age on the Diagnosis of Myocardial Infarction” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Gibson and McEvoy Regarding Article, “Influence of Age on the Diagnosis of Myocardial Infarction” William O. Gibson and John W. McEvoy William O. GibsonWilliam O. Gibson National Institute for Prevention and Cardiovascular Health, National University of Ireland Galway. Search for more papers by this author and John W. McEvoyJohn W. McEvoy https://orcid.org/0000-0001-6530-5479 National Institute for Prevention and Cardiovascular Health, National University of Ireland Galway. Search for more papers by this author Originally published24 Apr 2023https://doi.org/10.1161/CIRCULATIONAHA.122.062836Circulation. 2023;147:1312–1313To the Editor:We commend Lowry et al on their recent retrospective analysis of age-adjusted, sex-specific 99th percentile upper reference limits for high-sensitivity (hs) troponin-I in the High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) trial.1,2 The authors found that, compared with currently recommended sex-specific 99th percentile upper reference limits, the use of age-adjusted, sex-specific 99th percentile upper reference limits improved specificity (91.3% versus 82.6%) and positive predictive value (59.3% versus 51.5%) for myocardial infarction (MI) diagnosis in older adults. However, these improvements come at the cost of a significant reduction in sensitivity.In addition to reduced sensitivity, the authors cite a number of concerns in their discussion (p 1142) when recommending against age-adjusted hs-troponin 99th percentile upper reference limits. However, we humbly submit that most of the concerns expressed suggest conflation of various issues unrelated to upper reference limits.First, hs-troponin concentrations higher than the 99th percentile upper reference limit simply indicate the presence of myocardial injury.3 Myocardial injury is a numeric construct used to distinguish normal from abnormal hs-troponin concentrations (note that a 97.5th percentile is used for this purpose for nearly all other laboratory analytes). These 99th percentiles are derived from people without any comorbidities; age-adjusted or not, they cannot disadvantage older adults with fewer comorbidities by nature.Second, using the 99th percentile threshold for ascertaining abnormality in hs-troponin concentration has nothing to do with prognosis or thresholds that confer risk. If we chose myocardial injury thresholds based on prognosis, we would have to use thresholds far lower than the 99th percentile.4Third, and most important, myocardial injury is not MI. Indeed, MI diagnosis requires 3 steps, of which establishing the presence of myocardial injury using a 99th percentile hs-troponin upper reference limit is just one.5 To confirm the diagnosis of MI, it is necessary to determine whether the myocardial injury is acute with dynamic hs-troponin concentrations and whether there is concomitant acute myocardial ischemia.It is for this third reason that we believe retrospective studies testing the performance of newly proposed hs-troponin 99th percentile upper reference limits have inherent flaws. Clinicians cannot by nature be blinded to the hs-troponin 99th percentiles that are in prospective clinical use during the study period (during High-STEACS, this was either a sex-specific or generic 99th percentile). Because of this, the actions taken to ascertain the last 2 steps in MI diagnosis (ie, is the injury acute? and is acute ischemia present?) are heavily influenced by the original 99th percentile in prospective use during a given study. We don’t know how the new 99th percentile (in this case, an age-adjusted, sex-specific one) being retrospectively tested would have changed behavior in ascertaining the last 2 steps of MI diagnosis. In other words, the same clinical course may not have been followed had the age-adjusted 99th percentile upper reference limit been applied prospectively. Indeed, if it had been, it seems plausible that fewer older patients would be exposed to the same level of further testing (eg, repeat either hs-troponin or ischemia tests) based on their initial hs-troponin result.Therefore, only prospective testing of new 99th percentile upper reference limits can truly determine their diagnostic performance and overall discrimination for MI.Article InformationDisclosures None.FootnotesCirculation is available at www.ahajournals.org/journal/circReferences1. Lowry M, Doudesis D, Wereski R, Kimenai D, Tuck C, Ferry A, Bularga A, Taggart C, Lee KK, Chapman AR, et al. Influence of age on the diagnosis of myocardial infarction.Circulation. 2022; 146:1135–1148. doi: 10.1161/CIRCULATIONAHA.122.059994LinkGoogle Scholar2. Shah A, Anand A, Strachan F, Ferry A, Lee K, Chapman A, Sandeman D, Stables CL, Adamson PD, Andrews JPM, et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial.Lancet. 2018; 392:919–928. doi: 10.1016/S0140-6736(18)31923-8CrossrefMedlineGoogle Scholar3. McCarthy C, Raber I, Chapman A, Sandoval Y, Apple F, Mills N, Januzzi JL. Myocardial injury in the era of high-sensitivity cardiac troponin assays.JAMA Cardiology. 2019; 4:1034. doi: 10.1001/jamacardio.2019.2724CrossrefMedlineGoogle Scholar4. Parikh RH, Seliger SL, de Lemos J, Nambi V, Christenson R, Ayers C, Sun W, Gottdiener JS, Kuller LH, Ballantyne C, et al. Prognostic significance of high-sensitivity cardiac troponin T concentrations between the limit of blank and limit of detection in community-dwelling adults: a metaanalysis.Clin Chem. 2015; 6:1524–1531. doi: 10.1373/clinchem.2015.24416CrossrefGoogle Scholar5. Thygesen K, Alpert J, Jaffe A, Chaitman B, Bax J, Morrow D, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018).J Am Coll Cardiol. 2018; 72:2231–2264. doi: 10.1016/j.jacc.2018.08.1038CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails April 25, 2023Vol 147, Issue 17 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.062836PMID: 37093972 Originally publishedApril 24, 2023 PDF download Advertisement SubjectsMyocardial InfarctionUltrasound