The manufacturer-recommended upper limit of normal (ULN) of high-sensitivity cardiac troponin I (hs-cTnI) assays is significantly lower than the hs-cTnI concentration present in patients, according to research published in BMJ.
These data suggest that greater scrutiny is needed in evaluating hs-cTnl levels for excluding or diagnosing acute myocardial infarction (AMI).
A total of 20,000 consecutive inpatients and outpatients (median age, 61 years) from the University Hospital Southampton NHS Foundation Trust in Southampton, United Kingdom, were enrolled in the study. During routine or specific blood testing, concentrations of hs-cTnI were recorded using the Beckman Coulter Access AccuTnI+3 assay. For the purposes of their analysis, researchers analyzed the distribution of hs-cTnI levels in all participants as well as the 99th percentile.
The hs-cTnI ULN quoted by the manufacturer was 40 ng/L compared with the 99th percentile of 296 ng/L. Concentrations of hs-cTnI were higher than the manufacturer-quoted concentration in approximately 1 of 20 patients. When researchers excluded those with a diagnosis of AMI, as well as patients who had hs-cTnI measured for clinical reasons, the investigators observed a 189 ng/L ULN for the 99th percentile. In addition, the 99th percentile was higher for inpatients than it was for outpatients (563 ng/L vs 65 ng/L, respectively).
Patients who were admitted to the emergency department had a 6.07% higher 99th percentile (215 ng/L) compared with the recommended ULN. Independent predictors of patients having a concentration of hs-cTnI greater than the recommended ULN included advancing age (odds ratio [OR], 1.03; 95% CI, 1.03-1.04), male sex (OR, 1.33; 95% CI, 1.14-1.54), and decreasing estimated glomerular filtration rate (OR, 0.98; 95% CI, 0.97-0.98; P <.001 for all).
Two study limitations included the observational nature of the study as well as the lack of clinical outcomes data.
Findings from this study “highlight the need for clinical staff to interpret hs-cTnI concentrations carefully and systematically when making a diagnosis of acute myocardial infarction, particularly type 1 myocardial infarction,” the researchers concluded.
Disclosures: All authors declared support from Beckman Coulter for the submitted work. Dr Curzen reports the receipt unrestricted research grants, speaker or consultancy fees, and travel sponsorships from several companies. For a complete list of these disclosures, please see the full text of the study.
Mariathas M, Allan R, Ramamoorthy S, et al. True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study.BMJ. 2019;364:l729.