Koganti, Sudheer; (2018) A flow cytometric and optical coherence analysis of the role of microparticles as determinants of plaque instability in acute coronary syndrome (FOAM study). Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Introduction: Microparticles (MPs) are implicated in the pathogenesis of coronary artery disease (CAD). / Aims: To determine whether circulating MPs correlate with high-risk coronary atherosclerotic plaque phenotype. / Methods: 25 patients with CAD undergoing percutaneous coronary intervention (PCI) were recruited; 13 were diagnosed to have acute coronary syndrome (ACS) & 12 with stable angina (SA). We characterized and compared coronary atherosclerotic plaque burden and vulnerable plaque phenotype by three-vessel optical coherence tomography (OCT) between ACS and SA groups. Endothelial (EMPs), platelet (PMPs), Neutrophil (NMPs), tissue factor (TFMPs) and smooth muscle (SMMPs) were quantified by flow cytometry, compared between groups pre PCI, post PCI, at days 1,7, 30 and 180. Pre and post PCI MPs measured on day 1 were correlated with OCT parameters. The levels of total and individual phenotypes of MPs were also compared based on presence or absence of thin cap fibroatheroma (TCFA) – a feature of plaque vulnerability. Procoagulant potential of MPs was determined by measuring thrombin generation assay (TGA) at above mentioned time points and compared between ACS and SA groups and also with disease free controls. / Results: OCT analysis revealed that ACS patients had more vulnerable features. The total AnnexinV+ MP (ANV+MP) levels were similar in ACS and SA groups at baseline, peaked immediately after PCI and were at their lowest on day 1. At six months CD54+EMPs [Median 9.9 (IQR 3.8,18.7) Vs. 2.6 (0.7, 5.2); p=0.008] and CD62p+PMPs [3.6 (1.2, 6.7) vs. 0.7 (0.4, 2.7); p=0.03] were significantly elevated in the ACS cohort. Patients with CAD showed abnormal thrombograms when compared to controls. Furthermore, thrombin parameters remained abnormal in ACS & SA patients at 6 months as demonstrated on AUC. Patients with TCFA exhibited enhanced thrombogenecity. / Conclusion: MPs may have a role as novel biomarkers in identifying vulnerable patients. Patients with TCFA expressed enhanced thrombogenecity irrespective of clinical presentation suggesting vulnerability.

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