title: Accuracy of biomarkers to diagnose acute cardiac ischemia in the emergency department: a meta-analysis.
abstract: OBJECTIVE
  We sought to evaluate quantitatively the evidence on the diagnostic performance of presentation and serial biochemical markers for emergency department diagnosis of acute cardiac ischemia (ACI), including acute myocardial infarction (AMI) and unstable angina.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of the English-language literature published between 1966 and December 1998. We examined the diagnostic performance of creatine kinase, creatine kinase-MB, myoglobin, and troponin I and T testing. Diagnostic performance was assessed by using estimates of test sensitivity and specificity and was summarized by summary receiver-operating characteristic curves.
  
  
  RESULTS
  Only 4 studies were found that evaluated all patients with ACI; 73 were found that focused only on a diagnosis of AMI. To diagnose ACI, presentation biomarker tests had sensitivities of 16% to 19% and specificities of 96% to 100%; serial biomarker tests had sensitivities of 31% to 45% and specificities of 95% to 98%. Considering only the diagnosis of AMI, presentation biomarker tests had summary sensitivities of 37% to 49% and summary specificities of 87% to 97%; serial biomarker tests had summary sensitivities of 79% to 93% and summary specificities of 85% to 96%. Variation of test sensitivity was best explained by test timing. Longer symptom duration or time between serial tests yielded higher sensitivity.
  
  
  CONCLUSIONS
  The limited evidence available to evaluate the diagnostic accuracy of biomarkers for ACI suggests that biomarkers have very low sensitivity to diagnose ACI. Thus, biomarkers alone will greatly underdiagnose ACI and will be inadequate to make triage decisions. For AMI diagnosis alone, multiple testing of individual biomarkers over time substantially improves sensitivity, while retaining high specificity, at the expense of additional time. Further high-quality studies are needed on the clinical effect of using biomarkers for patients with ACI in the ED and on optimal timing of serial testing and in combination with other tests.
authors.affiliation: Evidence-based Practice Center, Division of Clinical Care Research, New England Medical Center, Boston, MA 02115, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Balk
authors.forename: J P
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: D
authors.initials: D
authors.lastname: Salem
authors.forename: P W
authors.initials: PW
authors.lastname: Chew
authors.forename: J
authors.initials: J
authors.lastname: Lau
mesh_terms: D000208:Acute Disease; D000789:Angina, Unstable / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology; D015982:Bias; D015415:Biomarkers / Q000097:blood*; D003402:Creatine Kinase / Q000097:blood*; D052279:Creatine Kinase, MB Form; D004638:Emergency Treatment / Q000379:methods* / Q000592:standards*; D019317:Evidence-Based Medicine; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology; D009211:Myoglobin / Q000097:blood*; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity; D013997:Time Factors; D014218:Triage / Q000379:methods / Q000592:standards; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D009211:Myoglobin; D019210:Troponin I; D020107:Troponin T; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form