title: Normal plasma levels of cardiac troponin I measured by the high-sensitivity cardiac troponin I access prototype assay and the impact on the diagnosis of myocardial ischemia.
abstract: OBJECTIVE
  This study sought to evaluate the analytical and clinical performance of the novel hypersensitive cardiac troponin I (cTnI) prototype assay from Beckman Coulter (Fullerton, California).
  
  
  BACKGROUND
  Studies on patients with acute coronary syndromes and on seemingly healthy subjects have shown that even very minor elevations of cardiac troponins are associated with an increased risk of death. However, the normal plasma levels of cardiac troponins are still not known.
  
  
  METHODS
  cTnI plasma levels were measured in 542 healthy subjects, 319 men (age 59.9 +/- 11.8 years) and 213 women (age 59.8 +/- 13.1 years), and in 1,503 randomly selected patients of the GUSTO IV (Global Utilization of Strategies To open Occluded arteries IV) cohort with unstable angina and non-ST-segment elevation myocardial infarctions (MIs).
  
  
  RESULTS
  The cTnI levels at 10% coefficient of variation and 20% coefficient of variation imprecision were 0.0033 and 0.0016 microg/l, respectively. The cTnI levels were measurable in >95% of the healthy subjects. The median level of healthy subjects <60 years of age was 0.0032 microg/l (range 0.0011 to 0.0079 microg/l) with the 99th percentile being 0.010 microg/l. No sex differences were observed. A receiver-operator characteristic curve analysis showed an optimal discrimination between healthy subjects and patients at 0.0064 microg/l with a sensitivity of 84.8% (95% confidence interval: 82.8% to 86.6%) and specificity of 89.7% (95% confidence interval: 86.8% to 92.2%). Outcomes as to death and/or MI were significantly different at this level (p < 0.01) in the GUSTO IV cohort.
  
  
  CONCLUSIONS
  The novel high-sensitivity cTnI prototype assay from Beckman Coulter allows for the first time the measurement of cTnI levels in almost all healthy subjects. Our data indicate that the assay may be a powerful aid in the diagnosis and outcome prediction of patients with suspected myocardial ischemia and question any definition of myocardial infarction.
authors.affiliation: Department of Medical Sciences, University of Uppsala, Sweden. per.venge@medsci.uu.se
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: Nina
authors.initials: N
authors.lastname: Johnston
authors.forename: Bertil
authors.initials: B
authors.lastname: Lindahl
authors.forename: Stefan
authors.initials: S
authors.lastname: James
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I