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True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study

BMJ 2019; 364 doi: (Published 13 March 2019) Cite this as: BMJ 2019;364:l729
  1. Mark Mariathas, cardiology research fellow1,
  2. Rick Allan, operations manager2,
  3. Sanjay Ramamoorthy, emergency medicine consultant3,
  4. Bartosz Olechowski, cardiology research fellow1,
  5. Jonathan Hinton, cardiology research fellow1,
  6. Martin Azor, business information manager4,
  7. Zoe Nicholas, research coordinator1,
  8. Alison Calver, interventional cardiology consultant5,
  9. Simon Corbett, interventional cardiology consultant5,
  10. Michael Mahmoudi, associate professor of interventional cardiology1 5,
  11. John Rawlins, interventional cardiology consultant5,
  12. Iain Simpson, interventional cardiology consultant5,
  13. James Wilkinson, interventional cardiology consultant5,
  14. Chun Shing Kwok, clinical lecturer in cardiology6,
  15. Paul Cook, biochemistry consultant2,
  16. Mamas A Mamas, professor of cardiology6,
  17. Nick Curzen, professor of interventional cardiology1 5 7
  1. 1Coronary Research Group, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  2. 2Biochemistry Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  3. 3Emergency Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  4. 4Coding Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  5. 5Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  6. 6Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University, Stoke on Trent, UK
  7. 7Faculty of Medicine, University of Southampton, Southampton, UK
  1. Correspondence to: N Curzen, E Level North Wing, University Hospital Southampton NHS Trust, Southampton SO16 6YD, UK nick.curzen{at} (or @NickCurzen on Twitter)
  • Accepted 8 February 2019


Objective To determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital.

Design Prospective, observational cohort study.

Setting University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017.

Participants 20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons.

Main outcome measures Distribution of hs-cTnI concentrations of all study participants and specifically the 99th centile.

Results The 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer’s quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN.

Conclusions Of 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation.

Trial registration NCT03047785.


  • Contributors: MM and NC performed the literature search and drew the figures. MM, RA, ZN, PC, and NC designed the study. MM, RA, SR, BO, JH, MA, ZN, AC, SC, MM, JR, IS, JW, CSK, PC, and NC collected the data. All authors contributed to data analysis, data interpretation, and writing the paper. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. NC, MM, PC, ZN, and RA are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: Beckman Coulter (Brea, CA, USA) provided an unrestricted research grant for the study. The company had no involvement in the data collection, analysis or interpretation; trial design; or patient recruitment. The company had no role in the writing of the manuscript or decision to submit it for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: support from Beckman Coulter for the submitted work; NC received unrestricted research grants from Boston Scientific, Haemonetics, Heartflow, Beckmann Coulter; speaker fees or consultancy fees from Haemonetics, Abbot Vascular, Heartflow, and Boston Scientific; and travel sponsorship from Biosensors, Abbot, Lilly/D-S, St Jude Medical, and Medtronic.

  • Ethical approval: This research project was undertaken according to the principles of Good Clinical Practice and the Declaration of Helsinki. The study was approved by the local ethical committee who then referred it to the Health Research Authority UK and its independent Confidentiality Advisory Group for further approval (REC reference: 17/SC/0042; IRAS project ID: 215262).

  • Data sharing: No additional data are available.

  • The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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