title: Direct comparison of clinical decision limits for cardiac troponin T and I.
abstract: OBJECTIVE
  The 99th percentile upper reference limit of high-sensitivity cardiac troponin (hs-cTn) from a healthy reference population is used for diagnosing acute myocardial infarction (AMI). Accepted current thresholds of hs-cTnT (Roche) and hs-cTnI (Abbott) are 14 and 26 ng/L, respectively. Since thresholds for hs-cTnT and hs-cTnI were derived from different reference cohorts it is unclear whether they are biologically equivalent. We directly assessed sex-specific and age-specific 99th percentile upper reference limits of hs-cTnT and hs-cTnI in a single reference cohort, to investigate whether current divergent thresholds of hs-cTnT and hs-cTnI stem from intrinsic assay differences or reflect cohort variation.
  
  
  METHODS
  A healthy reference population was derived from a population-based cohort (the Maastricht Study: n=3451; age: 40-75 years). Individuals with diabetes mellitus, a history of cardiovascular disease, cardiac ischaemia on ECG, N-terminal pro-brain natriuretic peptide >125 ng/L or estimated glomerular filtration rate <60 mL/min/1.73 m(2) were excluded. Non-parametric analyses were performed to assess 99th percentile upper reference limits.
  
  
  RESULTS
  1540 individuals were included in the healthy reference population (age 57±8 years, 52.4% women). Overall 99th percentile upper reference limits of hs-cTnT and hs-cTnI were 15 and 13 ng/L, respectively. Upper reference limits were higher in men than women (hs-cTnT: 16 vs 12 ng/L), (hs-cTnI: 20 vs 11 ng/L) and increased with age.
  
  
  CONCLUSIONS
  Direct comparison reveals numerically similar thresholds for hs-cTnT and hs-cTnI assays. This finding is in line with recently reported underdiagnosis of AMI with the current decision limit of 26 ng/L for hs-cTnI, especially among women. Downwards adjustment of the hs-cTnI threshold, differentiated for sex, would equalise clinical decision limits for both assays, and may prevent further underdiagnosis of AMI.
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Kimenai
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands.
authors.forename: Ronald M A
authors.initials: RM
authors.lastname: Henry
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands.
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Epidemiology, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands.
authors.forename: Miranda T
authors.initials: MT
authors.lastname: Schram
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of Clinical Chemistry, Gelre Hospital, Apeldoorn, The Netherlands.
authors.forename: Jeroen D E
authors.initials: JD
authors.lastname: van Suijlen
authors.affiliation: Department of Clinical Chemistry, Gelre Hospital, Apeldoorn, The Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Niens
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands.
authors.forename: Simone J S
authors.initials: SJ
authors.lastname: Sep
authors.affiliation: Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands.
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Steven J R
authors.initials: SJ
authors.lastname: Meex
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D015415:Biomarkers / Q000097:blood; D000066491:Clinical Decision-Making / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis*; D011446:Prospective Studies; D012016:Reference Values; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I; D020107:Troponin T