Is the Current Threshold for Diagnosis of 'Abnormality', Including Non ST Elevation Myocardial Infarction, Using Raised High Sensitivity Troponin Appropriate for a Hospital Population? The CHARIOT Study

Objective: To define the 99th percentile of high sensitivity cardiac troponin I (hs-cTnI) concentration for a hospital population. Design: Prospective study of 20,000 consecutive patients undergoing blood sampling for any reason at a large teaching hospital. Setting: University Hospital Southampton NHS Trust (UHS). Participants: 20,000 consecutive individuals, inpatient or outpatient, undergoing blood tests at UHS for any clinical reason. Hs-cTnI concentrations (Beckman Coulter Access AccuTnI 3 assay) were nested for analysis in all cases except those in whom the supervising physician had requested hs-cTnI for clinical reasons. Main outcome measures: Distribution of hs-cTnI concentrations of all study patients. Results: The 99th percentile of hs-cTnI for the whole population (n=20,000) was 296 ng/L, compared to a manufacturer quoted 99th percentile of 40 ng/L (currently used clinically as the upper limit of normal, ULN). In 1 in 20 (5.4%, n=1080) of the total population hs-cTnI concentrations were above 40 ng/L. After exclusion of individuals diagnosed with an acute myocardial infarction (AMI) (n=122), or those in whom troponin was requested (n=1707), the 99th percentile of the remainder (n=18,171) was 189 ng/L. The 99th percentile for inpatients (n=4759) and outpatients (n=9280) was 563 ng/L and 65 ng/L, respectively. Patients from the emergency department (n=3706) had a 99th percentile of 215 ng/L, with 6.1% (n=491) above the quoted ULN. 39% (n=48) of all individuals from the critical care units (n=123) and 15.7% (n=87) of all medical inpatients had a hs-cTnI concentration above the quoted ULN. Conclusions: In 20,000 consecutive patients undergoing a blood test for any reason at this hospital 1 in 20 have a hs-cTnI above the manufacturer quoted ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the manufacturer's ULN to diagnose AMI. The use of hs-cTn to diagnose AMI in any patient without a typical history may be flawed. Funding Statement: Unrestricted Research Grant – Beckman Coulter Declaration of Interests: M. Mariathas – none declared, R. Allan – none declared, B. Olechowski – none declared, S. Ramamoorthy – none declared, M. Azor – none declared, Z. Nicholas – none declared, A. Calver – none declared, S. Corbett – none declared, M. Mahmoudi – none declared, J. Rawlins – none declared, I. Simpson – none declared, J. Wilkinson – none declared, C. Kwok- none declared, M. Mamas- none declared, P. Cook – none declared, N. Curzen – unrestricted research grants from: Boston Scientific; Haemonetics; Heartflow; Beckmann Coulter. Speaker fees/consultancy from: Haemonetics, Abbot Vascular; Heartflow; Boston Scientific. Travel sponsorship – Biosensors, Abbot, Lilly/D-S; St Jude Medical, Medtronic. Ethics Approval Statement: 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 (HRA) UK for further approval (Rec reference: 17/SC/0042, IRAS project ID: 215262). The method did not require knowledge or consent from patients.