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

Abstract

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: Clinicaltrials.gov NCT03047785.

Fig 1

Log distribution of high sensitivity cardiac troponin I (hs-cTnI) concentration in whole study population (n=20 000) and in final study population (n=18 171). ULN=manufacturer’s recommended upper limit of normal for hs-cTnI concentration (>40 ng/L)

Fig 2

Proportion of patients with high sensitivity cardiac troponin I concentration greater than manufacturer’s recommended upper limit of normal (ULN=40 ng/L), according to location when the biochemistry test was requested

Fig 3

Upper limit of normal concentration of high sensitivity cardiac troponin I (ULN=40 ng/L) according to age of patients