Extra-coronary arterial disease: incidence, projected future burden, risk factors and prevention

Vascular disease is the leading cause of death and disability worldwide. Incidence, risk factors, and outcome of coronary artery disease have been extensively studied, but there are fewer data on other forms of arterial disease, including carotid, aortic, visceral, and peripheral arterial disease. Although the burden of these diseases may be increasing due to the ageing population, we lack the most basic epidemiological data on which to base clinical decisions on individual patients (short and long-term prognosis); local service provision (current incidence and projected future burden); public health / screening initiatives (age and sex-specific incidence, risk factors, and outcome); and with which to assess current levels of primary prevention (pre-morbid risk factor control). Indeed, it is this lack of data, rather than a lack of treatments that is the greatest barrier to effective prevention. I have contributed to, cleaned, and analysed data from the Oxford Vascular Study, a prospective, population-based study (n=92,728) of all acute vascular events (2002-2012), and the Oxford Plaque Study, a carotid atherosclerosis biobank of over 1000 carotid plaques, in order to study these conditions. For acute aortic disease, I aimed to assess the risk factors associated with acute abdominal aortic aneurysms (AAA) and the population impact of the current UK AAA screening programme; and the incidence, risk factors, outcome, and projected future burden of acute aortic dissection. For acute peripheral arterial disease, I assessed the risk factors associated with premature onset and poor outcome, together with current levels of primary prevention. For symptomatic carotid artery disease, I studied the timing and benefits of surgical intervention in the current era; and went on to assess whether underlying carotid plaque morphology can be used to improve stroke risk stratification and help explain why ocular and cerebral stroke types have vast differences in future ipsilateral stroke risk. I found that compared with the current UK AAA screening strategy (one-off scan for men aged 65), screening of male smokers at 65 and all men at 75 would prevent nearly four-times as many deaths and three-times as many life-years lost with 21% fewer annual scans. I have also shown that incidence of acute aortic dissection is higher than previous estimates, a third of cases are out-of-hospital deaths, and uncontrolled hypertension is the most significant treatable risk factor for this condition. For acute peripheral arterial disease, the presence of multiple atherosclerotic risk factors are associated with premature onset, and severity of ischaemia, pre-morbid renal dysfunction, cardiac failure, and diabetes mellitus are predictive of future limb loss and survival. A significant proportion of acute peripheral events are AF-related in high risk patients who were not pre-morbidly anticoagulated despite having no contraindications and being at low risk of bleeding. Symptomatic carotid artery disease currently accounts for <10% of incident cerebrovascular events, and only 40% of these patients undergo surgical intervention. Due to improvements in medical therapy and on-going delays to intervention, little benefit is currently obtained from intervening in patients with <70% stenosis. Ipsilateral stroke risk is correlated with several carotid plaque features in a time-dependent manner, confirming the potential utility of plaque morphology in risk stratification. In addition, plaques from patients with cerebral events were significantly more unstable and inflammatory than from those with ocular events, helping explain differences in stroke risk between these groups. My findings advance the understanding of these conditions that form the backbone of modern vascular surgical practice, and I hope will improve prevention, clinical management, and outcome for patients with vascular disease.