Carotid Artery Disease After Stroke (CADAS).
Carotid Artery Disease After Stroke (CADAS).
Stroke is a significant medical problem with 150,000 events occurring per year in the UK and
 incurring healthcare costs of £4 billion per year. Fifty percent of strokes will leave a
 lasting disability on first manifestation and 10-15% (roughly 16,500 per year) are unheralded
 ischaemic events in previously asymptomatic Carotid artery disease.

 Carotid Artery Disease is caused by the formation of an atherosclerotic plaque in the vessel.
 Stroke or TIA occurs when plaque or adherent thrombus breaks off and embolises to the brain,
 blocking off its blood supply. Hence, a carotid plaque is said to be symptomatic if it has
 caused a Stroke or TIA in the territory of the brain supplied by that vessel in the previous
 six months.

 Currently, the degree of stenosis (narrowing) of the artery by doppler ultrasound is the main
 assessment performed. Doppler ultrasound measures stenosis and elevation of blood flow
 velocity in the artery prior to surgical intervention. However, it has been shown that the
 degree of stenosis is a poor predictor of stroke as many asymptomatic patients have severe
 stenosis and many symptomatic patients have moderate stenosis. Stenosis is a two dimensional
 assessment of a 3-D structure.

 Other features of the plaque should be considered including the volume of the carotid plaque
 and its constituents. Carotid Plaque Volume has been measured in 339 individuals, with plaque
 volume being higher in symptomatic than asymptomatic individuals. In this study, plaque
 volume did not correlate with stenosis degree. No studies have been conducted measuring the
 change in carotid plaque volume and morphology following a stroke. This pilot study will
 perform serial duplex scans on recently symptomatic individuals over a 12 week period and
 observe the changes in Plaque Volume and morphology. This will attempt to prove that carotid
 plaque volume is a better predictor of stroke than stenosis. The investigators will also aim
 to identify other plaque features that may have an important role in predicting stroke risk.
 Documenting the timescale of change in plaque volume will aid us in defining appropriate
 timescales for treating the symptomatic population and when those having medical management's
 risk has returned to baseline. Observing the change in plaque immediately after stroke will
 improve our knowledge of the changes in plaques that lead to symptoms and may in the future
 help us predict which patients with asymptomatic carotid stenosis need operation.
Carotid Stenosis and stroke risk

 Although carotid stenosis is the primary factor used to determine stroke risk and clinical
 priority in carotid artery disease, stenosis is in fact a poor predictor of stroke risk.
 Specifically, in asymptomatic patients with >70% carotid stenosis, the risk of ipsilateral
 stroke is under 2% a year. Therefore in these patients the benefit of intervention with
 carotid endarterectomy is minimal, in simple terms around 32 CEA's would need to be
 undertaken to prevent just one stroke in carotid artery disease patients over a five year
 follow up period. This clearly indicates that carotid stenosis itself is a poor indictor of
 stroke risk.

 Several other factors have been proposed as potentially relevant to stroke risk determination
 in carotid artery disease.

 Carotid plaque volume

 Carotid plaque volume (CPV) is the actual volume of atherosclerotic plaque present within the
 carotid artery. CPV may impact on stroke risk in Carotid artery disease as an increased
 atherosclerotic burden may disrupt carotid flow leading to thrombus formation and subsequent
 embolisation leading to CVA.

 A recent pilot study recruiting over 200 patients demonstrated that CPV in patients
 undergoing CEA within four weeks of symptoms was almost double of that seen in asymptomatic
 patients, with mean CPV in the symptomatic group being 1.1cm3 compared with 0.68cm3 in the
 asymptomatic group (p<0.001). Interestingly, carotid plaque volume was also shown to fall
 rapidly following symptoms of cerebral ischemia from 1.1cm3 within four weeks of cerebral
 symptoms to 0.91cm3 at six weeks and a mean of only 0.62 cm3 more than eight weeks following
 symptoms. This data demonstrated that there may be a crucial link between CPV and
 cerebrovascular symptoms in carotid artery disease and therefore between CPV and stroke risk
 in the disease.

 Carotid Plaque Morphology

 Various studies have detailed carotid plaque histology to identify features that are related
 to cerebrovascular symptoms. The main features being; intra-plaque haemorrhage, plaque
 ulceration, fibrous cap thickness and lipid rich necrotic core. Fisher et al showed plaque
 ulceration was significantly more common in plaques in symptomatic patients. Xu et al also
 reported that disruption of the luminal surface, by fibrous cap rupture, intraplaque
 haemorrhage or ulceration is indicative of a high risk lesion. The project aims to identify
 these features on 3D duplex.

 3D Duplex

 3D duplex has been used to measure plaque volume and is proven to be reliable. The inter and
 intra observer variability have been shown to be low but increase with reducing amounts of
 total plaque volume. The study hypothesises that Carotid Plaque volume will correlate more
 with risk of stroke than the degree of stenosis.

 Antiplatelet Resistance

 All carotid patients are treated with antiplatelet agents, commonly aspirin or clopidogrel,
 to reduce the incidence of thrombus formation around plaques. This intervention is thought to
 reduce stroke risk by around 9% annually and is therefore a key therapy in the management of
 carotid artery disease. Research has suggested that up to 37% of the population may be
 resistant to the actions of antiplatelet agents; if this is true in carotid artery disease
 patients it would represent a severe shortfall in current treatment and the prevalence and
 impact of this resistance may also impact on the risk of stroke in CAD patients. Patients
 will be tested for antiplatelet resistance at two timepoints to establish if they have
 resistance to the agents but also to see the effect of the acute embolic event on the
 efficacy of antiplatelet agents.

 A recent pilot study involving 35 patients demonstrated a significant prevalence of
 antiplatelet resistance in CAD patients and showed an association between cerebrovascular
 symptoms and residual platelet aggregation. This further strengthens the hypothesis that
 antiplatelet resistance may be associated with stroke risk in CAD. Data from this project
 demonstrates that antiplatelet resistance may be prevalent in the CAD patient population and
 that the impact of this resistance, although potentially significant, is as yet not fully
 understood.

 Schedule of events

 The procedures will be performed at the following time intervals;

 -  < 7 days 3D Duplex + Platelet aggregometry

 -  Day 14 (+/- 2 days) 3D Duplex

 -  Day 28 (+/- 2 days) 3D Duplex

 -  Day 56 (+/- 2 days) 3D Duplex

 -  Day 84 (+/- 2 days) 3D Duplex + Platelet aggregometry
Inclusion Criteria:

 -  Patients with capacity to give informed consent. All patients who have suffered a
 Partial Anterior Circulatory Stroke (PACS) or Transient Ischaemic Attack (TIA).

 Carotid Stenosis >50%.

 Exclusion Criteria:

 -  Lacking capacity. Carotid Artery occlusion. Allergy to contrast agent. Significant
 disability or immobility such that participation would cause stress.