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Identification of significant coronary artery disease by the measurement of H-FABP (Heart-type Fatty Acid Binding Protein) for patients with normal troponin concentrations

Abdel-Rahman, Saif-El-Dean Tawfik (2015) Identification of significant coronary artery disease by the measurement of H-FABP (Heart-type Fatty Acid Binding Protein) for patients with normal troponin concentrations. M.D. thesis, University of Leeds.

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Objective: We intend to investigate the ability of H-FABP levels to identify significant coronary artery disease in low- to intermediate-risk patients with suspected acute coronary syndrome (ACS). Background: H-FABP is a small intracellular protein involved in the transport and buffering of fatty acids in cardiac myocytes. There is an increasing evidence base for the utility of H-FABP as a cardiac biomarker for the early diagnosis of ACS. Levels have been shown to provide incremental prognostic information about future risk of myocardial infraction (MI) and death, independent of traditional risk factors and troponin levels. Methods: 238 patients presenting with possible ACS were recruited as they attended the Emergency Department (ED) of a major UK teaching hospital. Venous blood samples were drawn at presentation, 90 minutes later, and after 12 hours from index symptoms. H-FABP was measured using the RANDOX Immunoturbidometric Immunoassay. Computerised axial tomography coronary artery calcium scoring (CTCS) was used as a marker of coronary atheroma burden, combined with clinical assessment for the detection of obstructive coronary artery disease (CAD). Results: There was a statistically significant positive correlation between H-FABP and CTCS, independent of age and renal function. Used on its own as a continuous variable, H-FABP was poor at predicting Agatston CTCS >10, and the clinical demonstration of obstructive coronary disease (areas under the ROC curve 0.6-0.7). When used as part of a multifactorial model to predict these endpoints H-FABP was, however, a more powerful predictor than some traditional risk factors such as smoking status, diabetes, hypertension, as well as renal function. H-FABP showed the greatest promise when used as a dichotomous variable within what we termed a ‘triple rule-out’ strategy. Here, H-FABP was used alongside the ECG and troponin to help identify patients at low risk of obstructive coronary artery disease, and tertiary events within a median follow-up period of 406 days (death from a cardiovascular cause, myocardial infarction, coronary revascularisation). Using a H-FABP cut-off at the 50th centile (3.16 μg/l), the triple rule-out strategy had a 96.4% negative predictive value (95% CI 86.6%-99.3%), and sensitivity of 83.3% (95% CI 50.8%-97.1%). 31% of the recruited population fell into the rule-out group. The triple rule-out strategy was validated for mortality on a cohort of 483 patients from the FAB2 study (Viswanathan et al., 2010). 19% of patients met rule-out criteria, with a 2.2% all-cause six year mortality, as compared to a 20.6% all-cause six year mortality for patients that did not. In the rule-out group no deaths were seen within the first 18 months. This equates to an all-cause six year mortality sensitivity of 97.5% (95% CI 90.5%-99.6%) and negative predictive value of 97.8% (95% CI 91.4%-99.6%). Conclusion: The analyses demonstrate the potential for H-FABP to be used as part of a triple rule-out strategy, guided by clinical assessment, alongside the ECG and troponin to identify low risk patients as they present to the ED. The strategy would benefit from external validation.

Item Type: Thesis (M.D.)
Keywords: heart-type fatty acid-binding protein, fatty acid-binding protein, H-FABP, FABP, accelerated, chest pain, discharge protocol, diagnostic protocol, rule, critical pathway, cardiac biomarker
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds)
The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds)
Depositing User: Dr Saif-El-Dean Tawfik Abdel-Rahman
Date Deposited: 03 Dec 2015 16:10
Last Modified: 21 Jan 2016 12:16
URI: http://etheses.whiterose.ac.uk/id/eprint/11387

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