title: Defining a reference population to determine the 99th percentile of a contemporary sensitive cardiac troponin I assay.
abstract: BACKGROUND
  Diagnosis of acute myocardial infarction (AMI) according to the universal definition is based on ischemic symptoms, imaging findings and elevated myocardial necrosis markers, preferably cardiac troponin I/T with diagnostic threshold representing the 99th percentile of a reference population. It is not clearly defined if this should be an unselected population-based or a healthy cohort with respect to cardiac diseases. Aim of the current study was to describe the distribution of troponin I using a sensitive assay and to evaluate the impact of cardiac diseases and cardiovascular risk factors in apparently healthy individuals.
  
  
  METHODS
  Troponin I was determined using a contemporary sensitive assay (TnI Ultra, Siemens) with 10% coefficient of variation (0.03 ng/mL) below the published 99th percentile (0.04 ng/mL) in 5000 participants (49.2% female) of the Gutenberg Health Study, a community-based, prospective, observational single-center cohort study. The calculated 99 th percentile cut-offs were tested in 1818 patients with suspected AMI.
  
  
  RESULTS
  Troponin I concentration representing the 99th percentile of the overall study population was 0.04 ng/mL. Excluding individuals with prevalent cardiovascular disease lowers the 99th percentile to 0.034 ng/mL. Exclusion of individuals with traditional risk factors or elevated natriuretic peptide leads to further reduction with 0.029/0.028 ng/mL. These lower cut-offs detect more patients at risk in individuals with suspected AMI. Correlations of troponin I with age, gender and traditional risk factors were observed.
  
  
  CONCLUSIONS
  Troponin I concentrations in apparently healthy individuals are dependent on prevalent cardiovascular diseases, traditional risk factors, gender and age. Application of corresponding cut-offs in diagnosis of AMI alters the group of patients potentially at risk.
authors.affiliation: Department of Medicine II, University Medical Center, Johannes Gutenberg University, Mainz, Germany. keller@chestpain.de
authors.forename: Till
authors.initials: T
authors.lastname: Keller
authors.forename: Francisco
authors.initials: F
authors.lastname: Ojeda
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.forename: Stergios
authors.initials: S
authors.lastname: Tzikas
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Sinning
authors.forename: Dirk
authors.initials: D
authors.lastname: Peetz
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D012737:Sex Factors; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D019210:Troponin I