Investigation of the population prevalence, risk factors, and stroke risk of asymptomatic carotid artery stenosis

Carotid artery disease causes 15-20% of all ischaemic strokes and is the main large artery cause of stroke, making it an important target for stroke prevention. Yet little is known about the contemporary prevalence and risk factors for this disease. While medical therapy and carotid revascularisation havw been used for over half a century in patients with carotid stenosis, the absolute benefits of asymptomatic carotid intervention have become less clear in the current era of effective cardiovascular medical therapy and declining stroke risks. This thesis examines the epidemiology of asymptomatic carotid artery disease, the procedural hazards and long-term efficacy of carotid endarterectomy among patients with a tight asymptomatic stenosis, and the contemporary absolute stroke risks of asymptomatic patients who are managed with effective medical therapy alone.
Risk factors for carotid artery disease were assessed using data from a large commercial screening registry. Between 2008 and 2013, 2.4 million apparently healthy US & UK adults were screened for carotid artery disease using duplex ultrasound. Logistic regression was used to examine associations of vascular risk factors with carotid artery disease, adjusted for age, sex, and country. Overall, 3% of screening attendees had carotid artery disease with a peak systolic velocity of ≥110 cm/s in the carotid arteries. Prevalence was strongly correlated with age and major cardiovascular risk factors, in particular smoking, systolic blood pressure and diabetes. The risks of higher body-mass index and abnormal cholesterol fractions were more moderate, but still clinically relevant.
The perioperative hazards and long-term efficacy of asymptomatic carotid endarterectomy were assessed by analysing individual patient data from 5226 patients randomised across three clinical trials. Asymptomatic carotid endarterectomy was associated with an initial 30-day stroke or death risk of about 3%. However this was later offset by substantial reductions in stroke risk. Successful carotid endarterectomy halved the 5-year stroke risk (from 11.8% to 5.8%) and the benefits were maintained to 10-years. Successful surgery halved the risks of both fatal and disabling strokes as well as minor strokes. The proportional benefits were not affected by cardiovascular medical therapy, though patients taking more intensive medical therapy had lower risks of stroke and therefore had more modest absolute benefits from surgery. The proportional benefits were similar across 23 different subgroups, as well as for patients with different predicted stroke risks as estimated by a novel risk score. Yet the absolute benefits varied across patients with different characteristics.
Those individuals at highest risk of stroke, according to presence of prior cerebral ischaemia and diabetes, received greater absolute benefits from early carotid endarterectomy.
Lastly, a prospective cohort study was designed and piloted to reliably estimate contemporary stroke risks of UK patients with medically managed carotid stenosis. 500 patients were recruited to the pilot from two NHS Trusts in less than a year. Detailed baseline characteristics and carotid artery duplex results have been obtained, and patients are now being followed-up for stroke using streamlined electronic data-linkage with central registries. This successful approach to rapidly recruiting large numbers of patients with contactless follow-up will inform the design of a full-scale study to clarify contemporary stroke risks of people with asymptomatic carotid stenosis.

Advisor: Halliday, A
Bulbulia, R
Lewington, S
Pan, H