title: Rule-In and Rule-Out of Myocardial Infarction Using Cardiac Troponin and Glycemic Biomarkers in Patients with Symptoms Suggestive of Acute Coronary Syndrome.
abstract: BACKGROUND
  Early rule-in/rule-out of myocardial infarction (MI) in patients presenting to the emergency department (ED) is important for patient care and resource allocation. Given that dysglycemia is a strong risk factor for MI, we sought to explore and compare different combinations of cardiac troponin (cTn) cutoffs with glycemic markers for the early rule-in/rule-out of MI.
  
  
  METHODS
  We included ED patients (n = 1137) with symptoms suggestive of acute coronary syndrome (ACS) who had cTnI, high-sensitivity cTnI (hs-cTnI), hs-cTnT, glucose, and hemoglobin A1c(Hb A1c) measurements. We derived rule-in/rule-out algorithms using different combinations of ROC-derived and literature cutoffs for rule-in and rule-out of MI within 7 days after presentation. These algorithms were then tested for MI/cardiovascular death and ACS/cardiovascular death at 7 days. ROC curves, sensitivity, specificity, likelihood ratios, positive and negative predictive values (PPV and NPV), and CIs were determined for various biomarker combinations.
  
  
  RESULTS
  MI was diagnosed in 133 patients (11.7%; 95% CI, 9.8-13.8). The algorithms that included cTn and glucose produced the greatest number of patients ruled out/ruled in for MI and yielded sensitivity ≥99%, NPV ≥99.5%, specificity ≥99%, and PPV ≥80%. This diagnostic performance was maintained for MI/cardiovascular death but not for ACS/cardiovascular death. The addition of hemoglobin A1c(Hb A1c) (≥6.5%) to these algorithms did not change these estimates; however, 50 patients with previously unknown diabetes may have been identified if Hb A1cwas measured.
  
  
  CONCLUSIONS
  Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A1cinto these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. ClinicalTrials.gov identifier: NCT01994577.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Colleen
authors.initials: C
authors.lastname: Shortt
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada; and the Children's Hospital of Eastern Ontario Research Institute, ON, Canada.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Clayton
authors.affiliation: Division of Emergency Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sherbino
authors.affiliation: Division of Cardiac Surgery, and Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Whitlock
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hill
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: McQueen
authors.affiliation: Division of Cardiology, and Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Mehta
authors.affiliation: Division of Cardiology, and Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: Devereaux
authors.affiliation: Division of Emergency Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worster
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; kavsakp@mcmaster.ca.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kavsak
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019210:Troponin I; D020107:Troponin T