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Title: Investigating the prevention of ischaemic stroke in carotid atherosclerosis
Author: King, Alice S.
ISNI:       0000 0004 2724 3993
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2012
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: Carotid stenosis causes 15-20% of all ischaemic strokes, which can be preceded by TIA or minor stroke but usually occur without warning. Risk of stroke is 10-15% in symptomatic disease and optimal medical treatment is unknown in the acute period prior to carotid endarterectomy (CEA) or where there are contraindications to surgery. In contrast, risk is now <2% per annum in asymptomatic disease; due to improved medical treatment however optimal treatments are unknown. Methods are required to identify asymptomatic patients at high risk of stroke to improve treatment by targeting CEA and intensive therapies to those who may benefit. The mechanism of these strokes in carotid atherosclerosis is predominantly thought to be due to thrombo-embolism. Transcranial Doppler (TCD) embolic signal (ES) detection may therefore be a useful technique in investigating the prevention of ischemic stroke. Data in symptomatic and occlusive disease suggest a haemodynamic mechanism may also contribute to stroke risk; however there are limited data in asymptomatic disease. Methods: In symptomatic carotid stenosis a randomised controlled trial was used to compare two anti- platelet regimens. A novel ambulatory TCD ES detection protocol and concurrent platelet aggregometry were used as surrogate markers. In asymptomatic carotid stenosis secondary analysis of a large multicentre international trial (ACES) was performed, analysing optimal protocols for TCD ES detection. In a sub study, TCD cerebrovascular reactivity (CVR) was also investigated. The influence of improvements in treatments on ES over time and changes in treatments over a two year follow-up period were also analysed to investigate prevention of ischemic stroke in asymptomatic carotid stenosis. Results: In symptomatic stenosis, aspirin in combination with either dipyridamole or clopidogrel reduced embolism to a similar extent. ES had temporal variation in ambulatory recordings. In asymptomatic carotid stenosis, ES detection on 2 baseline recordings is an independent risk prediction tool for ipsilateral stroke which was better than shorter recordings or one recording only. CVR did not predict risk but this lack of association may reflect a low number of endpoints. A trend, but non-significant decrease, in ES over time was observed despite changes in treatments. Higher blood pressure and absence of anti-platelet therapy were associated with risk of ipsilateral strokelTlA and any stroke/cardiovascular death. Conclusion: ES are surrogate markers in both symptomatic and asymptomatic carotid stenosis. In acute symptomatic atherosclerosis, clopidogrel or dipyridamole in addition to aspirin reduce embolism to a similar extent and may be useful for prevention of embolic ischemic stroke. In asymptomatics, ES on either of 2 baseline recordings predict 2 year risk of ipsilateral stroke, however there is insufficient data for the use of CVR. Improvements in treatments at baseline did not prevent ES and the technique may be useful to identify patients at high risk who may benefit from carotid endarterectomy to prevent future ischaemic stroke. ES detection may also be important to identify those at low risk to target treatments appropriately. Consistent use of anti-platelet therapy and control of blood pressure are important in the prevention of ischemic stroke and cardiovascular death in asymptomatic carotid stenosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available