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
