Predicting a late positive serum troponin in initially troponin-negative patients with non–ST-elevation acute coronary syndrome: Clinical predictors and validated risk score results from the TIMI IIIB and GUSTO IIA studies

Background Troponin testing is useful for evaluating patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker. Methods Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative. A score predicting late TnI rise in TIMI IIIB was developed using these factors and validated among patients in the GUSTO IIA study. Results Of 1342 subjects in TIMI IIIB, 200 (14.9%) were negative at baseline, but developed an elevated TnI (≥0.4 ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified: ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P < .001), presentation <8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P < .001), no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P = .001), no prior β-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008), unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation, presentation <8 hours from symptoms, and no prior percutaneous coronary intervention were given a score of 2 points, whereas a score of 1 point was assigned to the other factors. Among baseline TnI-negative patients, a rising score was paralleled by an increasing prevalence of late TnI rise from 0% (with a score of 0) to 69% (with a score of 9) (P < .001). In confirmation, the score was able to similarly predict late troponin T rise among 855 patients in the GUSTO IIA study (P < .0001). Conclusion Development of late troponin rise is common in non–ST-segment elevation acute coronary syndromes. Six easily ascertained variables may be used to identify those at higher risk for late rise in troponin levels after an initially negative presentation.