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Stroke is the third leading cause of death and a major cause of long-term morbidity in the United States. It is estimated that 500,000 strokes occur annually in the U.S., with an associated mortality rate of nearly 30%. In addition, roughly 50,000 patients in the U.S. will suffer a transient ischemic attack (TIA), and about one third of those will develop a subsequent stroke prior to institution of therapy. Unfortunately, most strokes occur without warning, and stroke survivors are frequently left markedly disabled, leading to a staggering financial and emotional burden to both patient and family - and to the health care system in general.

Risk Factors for Ischemic Stroke
Evaluation of Carotid Artery Disease
Surgical Treatment

Fortunately, our understanding of the etiology of stroke has increased dramatically in recent years. This newly gained information has essentially paralleled a more complete definition of the complex pathophysiology and epidemiology of atherosclerosis. Once thought to be a static or slowly progressive obstructive process, it is now clear that atherosclerosis is a dynamic, inflammatory disease that more commonly leads to symptoms secondary to plaque rupture with associated thrombosis, atheroembolism, or thromboembolism, rather than ischemia from a low-flow state.

The vast majority of strokes in the U.S. (85%) are related to ischemia (not hemorrhage) secondary to athero/thromboembolism. The most common origin of the embolic source is the extracranial carotid artery. Carotid atherosclerosis develops almost exclusively in the region of the carotid bulb and proximal internal carotid artery. There are many theories as to why this region is prone to atherosclerosis, but the most commonly accepted one suggests that the lateral arterial wall is exposed to an area of low shear stress, a common finding in areas of atherosclerosis. As the disease progresses, carotid artery plaques are generally characterized by marked inflammatory cell concentrations, lipid accumulation, calcification, and ulceration, with frequently associated intraplaque hemorrhage and/or thrombosis (particularly in symptomatic lesions).

In general, as the atherosclerotic burden increases - leading to carotid artery diameter reduction - the risk of active carotid disease, or stroke, increases as well. The explanation as to why higher degrees of stenoses equate with a higher risk of stroke is basically two-fold. First, larger plaques are generally unstable and more prone to higher rates of intraplaque hemorrhage and distal embolization. And second, higher rates of thrombus formation occur in areas of high shear stress - such as that which develops in a high-grade stenosis - leading to subsequent distal embolization.

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Risk Factors for Ischemic Stroke
The commonly identified risk factors that predispose patients to an ischemic stroke, in general, correlate with the well-established risk factors for the development of atherosclerosis. Of these risk factors, the most readily modifiable are hypertension, smoking, and hyperlipidemia. Patients with hypertension have 3 to 4 times higher relative risk of stroke. Other predictors of stroke include TIA's (as mentioned above), previous stroke, carotid bruit or defined stenosis, and others. These factors are either treatable or untreatable and are detailed in Table I.

Table I.  Risk factors for ischemic stroke

Advanced Age
Family history of stroke

Potentially Treatable
Cigarette smoking
Diabetes mellitus
Transient ischemic attacks
Previous stroke
Asymptomatic carotid bruit or stenosis
Cardiac disease
Aortic arch atheromatosis
Elevated homocysteine level
Use of oral contraceptives

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Patients with one or more risk factors for atherosclerosis probably have it in some form or another as the disease is not usually isolated to one vascular bed, but more commonly occurs as a 'pan-atherosclerotic' process. The onset of the disease is often insidious, but the presenting symptoms are most frequently dramatic, e.g. myocardial infarction, stroke, limb threatening ischemia, etc. Given the magnitude of the problem, the evaluation and management algorithm for patients with significant risk factors for, clinical symptoms of, or physical findings suggestive of carotid artery disease bears mentioning.

The accurate determination of the degree of carotid artery stenosis is important in the routine clinical assessment of patients with suspected or confirmed carotid artery disease. This information determines whether surgical referral and subsequent intervention are warranted, or if the patient is best served by the administration of an antiplatelet agent with serial follow-up. If a patient presents with hard signs or symptoms of embolic cerebrovascular disease - amaurosis fugax, focal paresis or plegia, or dysphasia - or an asymptomatic cervical bruit, then a carotid duplex ultrasound is warranted. Duplex ultrasonography has revolutionized the approach to peripheral vascular in general and carotid artery disease in particular.

In asymptomatic patients with documented high-grade carotid stenosis by duplex scan, most often a confirmatory test such as carotid MRA or cerebral angiography should be obtained. This allows both a confirmation of the duplex findings as well as a precise degree or stenosis and a definition of any anatomical abnormalities.

In symptomatic patients, the need for further imaging is more controversial. If a high-grade lesion is detected on duplex scan, and the patient has symptoms of active embolic carotid disease, there is evidence to suggest that additional imaging in no way effects the treatment of these patients, i.e. has no impact on the plan to perform carotid endarterectomy. Others recommend a confirmatory study for the same reasons cited in the asymptomatic lesion discussion.

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Symptomatic Carotid Artery Stenosis

The severity of carotid artery stenosis strongly correlates with the relative risk of stroke. Through the removal of atherosclerotic plaques, carotid endarterectomy (CEA) restores cerebral blood flow and reduces the risk of cerebral ischemia. While medical therapy clearly plays a role in the management of atherosclerosis in general and carotid artery disease in particular, the results from three major prospective contemporary studies provide compelling evidence for the benefit of CEA versus medical therapy alone. When performed by experienced surgeons, CEA, most prominently, improves the chance of stroke-free survival in high-risk symptomatic patients.

Asymptomatic Carotid Artery Stenosis

Asymptomatic carotid artery disease is highly prevalent in the general population, particularly the patient with evidence of other atherosclerotic disease and in the elderly. Compared with symptomatic stenosis, however, most available data suggest that asymptomatic carotid artery stenosis is associated with a relatively low risk of ipsilateral cerebral infarction. Patients with asymptomatic disease should be considered for surgery when the lesion has reached 70-80%.

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The vast majority of patients with carotid artery occlusive disease are asymptomatic and can be managed medically. Medical strategies may include the use of platelet agents, risk factor modification, and evaluation for other forms of atherosclerosis. In general, serial follow-up for carotid artery stenosis should be performed on an every sixth month basis. Signs and symptoms of early cerebral ischemia should be sought. A concomitant carotid duplex scan should be obtained to detect progression of carotid stenosis in an effort to identify those patients who may benefit from surgical intervention. All patients should be counseled as to the warning signs of TIA and stroke, and told to go to the closest Emergency Department immediately should they occur.

Surgery for symptomatic carotid artery stenosis has the greatest impact with regard to stroke reduction. However, patients with high grade asymptomatic carotid occlusive disease (>80%) also enjoy a long-term reduction in stroke risk after CEA. The outcomes from surgical intervention have clearly been linked to the experience of the surgeon performing the procedure. All surgeons undertaking CEA should be able to honestly discuss their operative results with their patients to allow the patient to make an informed choice.

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