Inflammation in atherosclerosis: exploring novel risk factors, prognostic markers and role of colchicine as an anti-inflammatory therapy in acute coronary syndromes
AuthorTong, David Chung Kiet
AffiliationMedicine (St Vincent's)
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2021-03-05. This item is currently available to University of Melbourne staff and students only, login required.
© 2018 Dr. David Chung Kiet Tong
Inflammation plays a crucial role in the pathophysiology of atherosclerosis and clinical manifestation of acute coronary syndromes (ACS). Despite optimal medical therapy and contemporary percutaneous coronary intervention (PCI) technology, ACS patients remain at heightened risk for recurrent events and adverse clinical outcomes. It is known that inflammation is a global phenomenon and inflammatory milieu is intensified during ACS. In addition, inflammation, microvascular dysfunction (MVD) and myocardial injury/oedema are independently associated with adverse cardiovascular outcomes in patients with ischaemic heart disease despite there been scarce evidence to suggest the potential links between them. Diagnosis of MVD and myocardial oedema involves cumbersome invasive catheterisation procedures and radiology scans, which may not be necessarily accessible to all patients. Therefore, there is a need to explore potential surrogate markers that are simple, readily available, reproducible and inexpensive. Furthermore, colchicine has recently gained attention as a potential anti-inflammatory therapy in cardiovascular disease. However, the safety and feasibility of long-term colchicine administration in ACS population has not been examined. The principle aims of this thesis were to delineate the associations between inflammation, microvascular injury and myocardial injury, to explore the utility and prognostic values of various biomarkers, and to examine the potential of colchicine as a novel anti-inflammatory therapy in ACS management. A number of study protocols were conducted to achieve the aims. These include assessing coronary microvascular function using pressure/temperature sensor guidewire in catheterisation laboratory, evaluating for presence of myocardial oedema on cardiac magnetic resonance (CMR) imaging, capturing long-term cardiovascular events in a cohort of ACS patients via telephone follow-up, and lastly conducting a double-blind, placebo-controlled randomised trial involving colchicine in ACS population. In summary, the main findings of this thesis are: (a) Inflammation is associated with MVD, and C-reactive protein (CRP) is a significant predictor of MVD. (b) Resting coronary microcirculatory status is related to degree of myocardial injury in patients with ischaemic heart disease. (c) An ischaemic ECG, peak serum troponin and CRP levels are significant predictors of myocardial oedema (d) Leukocyte parameters such as platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with long-term all-cause mortality in ACS patients. (e) Colchicine in addition to standard secondary prevention therapy can be safely administered in ACS population. (f) Long-term adherence to ACS guideline-recommenced medical therapy remains unsatisfactory. The findings of this PhD are novel and have potential implications for future risk-stratification and management strategies in patients presenting with ACS. Larger studies are warranted to validate the prognostic value and clinical utility of these biomarkers before they could be incorporated into current risk prediction models or utilised in routine clinical practice. Lastly, the colchicine feasibility study has paved the way for a large randomised controlled trial which is currently underway to assess the efficacy of colchicine in improving long-term cardiovascular outcomes in ACS patients.
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