Coronary microvascular function in patients with non-ST elevation acute coronary syndrome: impact of contemporary therapies and relationship with peripheral endothelial function

The role of coronary microvascular dysfunction (CMD) in the pathogenesis of ischaemic heart disease and in determining long-term prognosis is increasingly recognised. Coronary microvascular dysfunction has therefore emerged as an important therapeutic target in the contemporary management across the clinical spectrum of ischaemic heart disease. However, due to a lack of a reliable traditional ‘gold-standard’ test for CMD, optimal treatment remains undefined. Currently, there is still paucity of data on targeted therapies for CMD and their implications on long-term clinical outcomes, particularly in the setting of non-ST elevation acute coronary syndromes (NSTEACS). Recent technical advancements, such as the invasively derived index of microcirculatory resistance (IMR), may provide novel insights into the assessment and treatment of CMD. Endothelial dysfunction is understood to be a systemic process and is also independently predictive of adverse prognosis. Abnormal endothelial function has been confirmed on peripheral tissue biopsies in patients with CMD. Peripheral endothelial function is most commonly assessed using the non-invasive brachial reactivity or brachial artery flow-mediated vasodilation (FMD) technique, which has been shown to have a close relationship with coronary endothelial function. However, the relationship between brachial artery FMD and invasive measures of CMD, such as the IMR, has not been studied. The overall aims of this thesis were to evaluate acute and longitudinal changes in coronary microvascular function and peripheral endothelial function, their relationship, and their responses to contemporary therapies in patients with NSTEACS. In particular, the effects of antiplatelet agents (ticagrelor versus clopidogrel), percutaneous coronary intervention, smoking cessation, and statin treatment were examined. The studies in this thesis provided unique insights into the assessment and treatment of CMD and peripheral endothelial dysfunction in patients with NSTEACS