The Oxford Abdominal Aortic Aneurysm Study (OxAAA)
Project leader: Dr Regent Lee, Clinical Lecturer
The Oxford Abdominal Aortic Aneurysm Study (OxAAA) aims to improve our understanding of the underlying patho-physiology of aneurysm progression in humans. An abdominal aortic aneurysm (AAA) is a pathological ballooning of the abdominal aorta (which should normally be <20mm in diameter). Left untreated, it gradually expands and results in aneurysm rupture with internal haemorrhage. Ruptured AAAs kill over 6000 people in the UK per year. The NHS spends over £5m per year to monitor small AAAs (<55mm). The ability to predict future growth rate of AAAs will better inform the frequency of monitoring and timing of surgery for small AAAs. However, there is as yet no established method to predict AAA growth in individual patients.
Regent established the Oxford AAA study in late 2013 with the aim to develop an algorithm for the prediction of AAA growth. Regent and his colleagues prospectively recruited a cohort of AAA patients undergoing the routine NHS management pathway. In addition to collecting the clinical data, such as AAA size, they performed additional research assessments at each clinical encounter. These included blood sample collection and non-invasive assessment of systemic endothelial function by measuring flow mediated dilatation (FMD) of brachial artery. During AAA surgery, the team collects a range of tissue biopsy to enable mechanistic investigations.
Regent’s research focuses on applying proteomics techniques for the discovery of novel biomarkers. During his DPhil, he demonstrated a novel work flow which incorporated intravascular imaging with tissue and plasma proteomics to define novel biomarkers of atherosclerotic plaque rupture, which is the culprit event that underpins emergencies such as heart attacks. He is applying a similar workflow to discover novel circulating markers for predicting AAA growth.
The OxAAA study is gaining momentum. Regent and his colleagues have recently published the finding regarding FMD as a novel marker for AAA growth. This leads to a new direction for investigating endothelial dysfunction as a key mechanism in AAA pathophysiology, and forms the basis of an algorithm for the prediction of AAA growth in individual patients. The final phase of Regent’s CL post will focus on securing external funding to support longer-term investigations of this, and for a multicentre study to validate the algorithm.
September 2017