Rule-In and Rule-Out of Myocardial Infarction Using Cardiac Troponin and Glycemic Biomarkers in Patients with Symptoms Suggestive of Acute Coronary Syndrome

Clin Chem. 2017 Jan;63(1):403-414. doi: 10.1373/clinchem.2016.261545. Epub 2016 Nov 10.


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 A1c was measured.

Conclusions: Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A1c into these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. identifier: NCT01994577.

Publication types

  • Clinical Study
  • Multicenter Study

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / diagnosis*
  • Aged
  • Algorithms
  • Biomarkers / blood
  • Blood Glucose / analysis*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis*
  • ROC Curve
  • Troponin I / blood*
  • Troponin T / blood*


  • Biomarkers
  • Blood Glucose
  • Troponin I
  • Troponin T

Associated data