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Title: Role of MCRP in the clinical management and the pathophysiology of the acute coronary syndromes
Author: Austin, Catrin Rebeca
ISNI:       0000 0004 7659 2700
Awarding Body: Manchester Metropolitan University
Current Institution: Manchester Metropolitan University
Date of Award: 2018
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Introduction: The rise in emergency department admissions for chest pain necessitates a quicker and more specific test for the different acute coronary syndromes. For a non-ST elevated myocardial infarction (NSTEMI) diagnosis, the current Gold Standard requires at least one cTn (cTn) value above the 99th percentile of a reference population across 12h of serial testing. Current research suggests serum levels of monomeric C-reactive protein (mCRP) and ultra-high-sensitive cTn assays may rule out NSTEMI more rapidly. Aims: To develop a novel immunoassay for mCRP for use on clinical samples to assess its diagnostic accuracy for NSTEMI. The Singulex Clarity and the Abbott iSTAT point of care hs-cTnI assays were assessed against the standard laboratory assay from Roche® Diagnostics hs-cTnT assay for NSTEMI diagnosis using non-kinetic (0h, 3h and max values) and kinetic (Δabsolute, %Δbaseline and %Δmean) values and in combination with H-FABP and ECG ischaemia. Methods: A competitive immunoassay for mCRP was optimised, which became an ELISA with a commercial anti-CRP detection antibody. Diagnostic tests calculated the clinical sensitivity, specificity, positive predictive value and negative predictive value for non-kinetic and kinetic values with the aim of creating the highest clinical sensitivity possible for NSTEMI rule out. Patients were grouped into 3 risk groups and cut-offs were optimised for each group. Predictor composites of 0h cTn, cTn deltas, ECG ischaemia and H-FABP were used for NSTEMI diagnosis and prediction of 3 different composite outcomes at 30 days. Cox regression assessed the assays' and risk factors' utility in 30-day MACE prediction. Results: The mCRP immunoassay was not sensitive enough for physiological mCRP concentrations (LoD 2 μg/ml) and the inter-assay imprecision was too great to be clinically useful. The Roche and Singulex assays showed 100% sensitivity and NPV for kinetic values in intermediate risk groups and predictor composites. The Singulex assay had 100% sensitivity for non-kinetic values also but the iSTAT assay did not perform well as a rule out diagnosis tool. Singulex Δabsolute and prior angina were independent predictors for 30-day MACE. Discussion: The mCRP immunoassay had problems because the antibody was not commercially produced, had to be used at high concentrations and therefore is not suitable for a competitive immunoassay. The Singulex assay could be used for early rule out but its variability could limit its clinical utility. The iSTAT assay is a useful tool for identifying high-risk patients quickly and all assays performed better when patients were split into risk groups by 0h cTn levels. Multi-faceted diagnostic tools are becoming more prominent for NSTEMI diagnosis and rule out.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available