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Title: Early diagnosis and risk stratification of acute coronary syndromes
Author: Shand , James Alexander
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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The diagnosis of myocardial infarction (MI) requires the measurement of a rising or falling pattern of the biomarker troponin to above the 99th centile upper limit of the normal reference population. Conventional assays of troponin I and T lack sensitivity early after the onset of symptoms. Various early biomarkers of MI were therefore of research interest in this patient cohort Recent data suggests that early diagnosis is achievable with highly sensitive assays of troponin with sensitivity comparable to delayed sampling. We investigated whether early biomarkers of MI including highly sensitive troponin T (hsTnT) were superior to the current gold standard conventional troponin T assay in patients presenting within 12 and 6 hours after symptom onset. Additionally, we investigated the prognostic information these biomarkers provide alone and in combination with the GRACE score, a well validated risk prediction model. Overall, 609 patients with chest pain of possible cardiac origin presenting to the emergency department were enrolled in this prospective observational study. Both hsTnT and heart fatty acid binding protein (HFABP) were superior to the conventional troponin T assay for the diagnosis of MI within 6 hours of symptom onset. Furthermore, hsTnT provided greater net reclassification than HFABP. Optimal diagnostic performance was achieved through measurement of an absolute change in hsTnT of 7ng/L. HsTnT, highly sensitive CRP (hsCRP) and N-terminal pro-brain natriuretic peptide (NT-Pro-BNP) were multivariate predictors of a combined endpoint of death, MI, stroke, and heart failure hospitalisation at one year. Furthermore, low level increases in HsT nT, previously undetectable with the conventional troponin T assay, were significantly associated with the primary composite endpoint and death/MI. A modest but significant improvement in integrated discriminatory improvement combining GRACE score (calculated with hsTnT) with hsCRP and NT-Pro-BNP was demonstrated over GRACE score calculated with conventional troponin T for the prediction of Death/MJ at 1 year.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available