Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values Aaron J. Simpson, 1 Julia M. Potter, 1,2 Gus Koerbin, 1,3 Carmen Oakman, 1 Louise Cullen, 4,5 Garry J. Wilkes, 6 Samuel L. Scanlan, 7 William Parsonage, 5,8 and Peter E. Hickman 1,2* BACKGROUND: Many patients presenting to the emer- gency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. METHODS: We used the hs-cTnI assay from Abbott Di- agnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CV T ) and, knowing the assay analytical CV (CV A ), we could calculate within-person biological variation (CV i ), reference change values (RCVs), and absolute RCV delta cTnI concentrations. RESULTS: We had data sets on 283 patients. Men and women had similar CV i values of approximately 14%, which was similar at all concentrations 40 ng/L. The biological variation was not dependent on the time in- terval between sample collections (t = 1.5–17 h). The absolute delta critical reference change value was sim- ilar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value 5 ng/L, and 97% had values of 10 ng/L. CONCLUSIONS: With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS. © 2014 American Association for Clinical Chemistry Cardiac troponin is a core component in the diagnosis of acute myocardial infarction, with the need for a demonstrated rise or fall in concentration and at least 1 result above the 99th percentile with some clinical evi- dence of ischemia (1). Determining the 99th percentile can be problematic for a variety of reasons, but espe- cially because subclinical disease may cause artifactual increases in apparent cardiac troponin 99th percentile cut points (2, 3, 4 ). The majority of patients assessed in the emergency department (ED) 9 for possible acute coronary syn- drome (ACS) prove to have no cardiac cause for their presentation (5, 6 ). Only a small proportion of patients being assessed will have a cardiac troponin above the 99th percentile (5). According to international guide- lines (7, 8 ), the assessment process for possible ACS includes 2 or more blood samples collected for mea- surement of cardiac troponin concentration. Evidence suggests that the relative or absolute change in cardiac troponin concentration may be of particular value in assessing patients at risk for ACS in the Emergency De- partment (9). We identified patients discharged home from the ED who did not have the diagnosis of ACS and used the data from this population to calculate total CV (CV T ), biological variation (CVi), percentage reference 1 ACT Pathology, Garran, ACT, Australia; 2 Australian National University Medical School, Canberra, ACT, Australia; 3 University of Canberra, Can- berra, ACT, Australia; 4 Department of Emergency Medicine and 8 Depart- ment of Cardiology, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia; 5 Queensland University of Technology, Brisbane, QLD, Australia; 6 Department of Emergency Medicine, Calvary Hospital, Bruce, ACT, Aus- tralia; 7 Department of Emergency Medicine, The Canberra Hospital, Garran, ACT, Australia. * Address correspondence to this author at: ACT Pathology, Yamba Drive, Garran, ACT 2605, Australia. E-mail peter.hickman@act.gov.au. Received November 24, 2013; accepted February 20, 2014. Previously published online at DOI: 10.1373/clinchem.2013.219410 9 Nonstandard abbreviations: ED, emergency department; ACS, acute coronary syndrome; RCV, reference change value; cTnI, cardiac troponin I; LoD, limit of detection. Clinical Chemistry 60:6 848–854 (2014) Proteomics and Protein Markers 848 Downloaded from https://academic.oup.com/clinchem/article/60/6/848/5621533 by guest on 05 June 2022