Atherothrombotic Disease

The Big Heart Disease Lie

Most Effective Heart Disease Treatments

Get Instant Access

Pathogenesis and Pathophysiology. Atherothrombosis implies a reduction or occlusion of blood flow caused by a localized thrombotic process in one or more atherosclerotic cervicocranial arteries. Branching points of arteries are the predilection sites of development of atherosclerosis (Fig. 45-3 (Figure Not Available) ). In atherosclerosis, fibrous and muscular tissues of the vessel wall overgrow in the subintima, and fatty materials form plaques that can encroach on the lumen. Platelets adhere to the crevices in the plaques and form clumps that serve as nidi for the deposition of fibrin, thrombin, and clot. Plaques and ulcers are associated with denudation of the endothelium and decreased release of endothelium-releasing factors including nitric oxide. Endothelins can promote platelet activation and thrombus formation. Intraluminal thrombi are of different types: so-called "white clots," which are mainly composed of platelets and fibrin, and "red thrombi," which are red blood cells enmeshed in fibrin. White platelet clumps form most often in fast-moving streams, adhering to crevices and irregularities along the intimal surface. Fibrin-dependent red thrombi develop in slow-moving streams, for example, arteries with severe luminal narrowing. Narrowing of arteries decreases blood flow, leading to stagnation of the blood column and activation of clotting factors. Clot and fibrin-platelet clumps form and break off, blocking distal arteries and further impeding flow in the affected parent artery (see Fig. 45-3 (Figure Not Available) ). ^

Epidemiology and Risk Factors. Atherosclerosis affects chiefly the large extracranial and intracranial arteries (, Fig 45.-.4 ), but there are important sex and racial differences in the distribution and incidence of lesions at these sites. White men have more severe disease of the extracranial arteries, whereas in blacks, persons of Asian origin, and women there is a predilection for narrowing of the intracranial arteries. y

Patients with extracranial large artery disease also have a high incidence of coronary artery disease (angina pectoris

Figure 45-4 Sites of predilection for atherosclerotic narrowing; black areas represent plaqw(Adapted from Caplan LR: Stroke. Clinical Approach. Boston, Butterworth-Heineman, 1993.)

and myocardial infarction), peripheral vascular occlusive disease (claudication), hypertension, and hypercholesterolemia. Death is more often due to fatal coronary artery disease than stroke.

Clinical Features and Associated Disorders. Development of neurological deficits preceded by brief, frequent shotgun-like TIAs in the same vascular territory usually suggests atherothrombosis as the vascular mechanism. Stroke caused by a thrombotic process often develops during or just after sleep. Atherothrombotic infarctions are usually characterized by postural sensitivity of symptoms, occlusion or severe stenosis of a large artery, absence of distal embolus by angiography, infarct on CT or MRI near the border zone territory of the affected artery, and the presence of risk factors for atherosclerosis such as hypertension, diabetes mellitus, and smoking. The neurological symptoms and signs depend on the vessels involved and the regions of brain ischemia.

Differential Diagnosis and Evaluation. The diagnosis of large artery occlusive disease is based on the demographic and epidemiological situation of the patient, analysis of the time course of the brain ischemia, physical examination of the heart and neck vessels, and tests that define the anatomy and function of the cervicocranial arteries. Brain imaging (by CT or MRI) is usually important to define the presence, location, and size of any infarction and may show unexpected ("silent") infarcts not predicted from the history and physical examination. Ultrasound has now become the cornerstone of noninvasive vascular diagnosis. Duplex scans of the carotid and vertebral artery origins combined with color-flow Doppler ultrasound can define and quantify most extracranial carotid and vertebral artery (VA) lesions. TCD can detect many intracranial occlusive lesions, especially those involving the MCAs, intracranial VAs, and the posterior cerebral arteries (PCAs). TCD also yields information about the impact of occlusive extracranial lesions on intracranial blood flow. MRA and CTA are also helpful in imaging the large extracranial and intracranial arteries. When ultrasound and MRA or CTA are concordant and define the occlusive vascular lesions, catheter angiography is usually not necessary.

Management. The very basic goal of management of ischemic stroke patients in the acute phase is protection of the so-called penumbra zone. This zone comprises the brain tissues at risk of irreversible ischemic damage. Brain tissues adjacent to the ischemic core are often impaired functionally ("stunned"), but ischemia is potentially reversible if the circulation is restored soon enough. To achieve this goal, several therapies can be used: (1) occluded vessels can be recanalized (thrombolytic therapy) if possible, (2) blood volume and cerebral blood flow can be maximized and blood viscosity can be reduced, (3) perfusion pressure must be maintained sufficiently (by careful control of blood pressure, reduction of cerebral edema, and lowering of intracranial pressure), and (4) the progression of occlusive processes should be blocked using anticoagulants and agents that alter platelet function in some instances. All these measures should be guided by the severity and reversibility of the lesion, the nature, location, and severity of the underlying stroke mechanism, and the viscosity and coagulability of the blood. Recanalization is usually performed by thrombolysis and will be discussed later in this chapter. Hemodilution therapy decreases blood viscosity by lowering the hematocrit level. Blood pressure should not be aggressively lowered during the acute phase, since this decreases pressure in the collateral channels and may extend the infarct. Various neuroprotective agents are presently under study.

For prevention of recurrence of ischemia in the future, prophylactic treatment should be guided by the mechanism of the stroke. Theoretically, red clots would respond more to warfarin anticoagulants and heparin, and white clots would be better prevented with platelet antiaggregants, such as aspirin. Surgery (endarterectomy), angioplasty, or warfarin may be indicated for patients with tight stenotic lesions and important tissue at risk for further ischemia. The choice of warfarin versus surgery or angioplasty depends on the accessibility of the lesions to treatment, the risk of surgery and angioplasty, the patient's wishes, the likelihood of the patient's compliance with anticoagulant usage, and any contraindication to the use of anticoagulants. y Heparin may be used for as long as 2 to 3 weeks to prevent propagation and embolization of clot. Long-term warfarin use is usually not needed after the clot organizes and adheres to the vessel wall in atherothrombotic stroke (usually 3 to 4 weeks). Aspirin, 325 mg or more per day, can prevent platelet-fibrin emboli in patients with minor or moderate stenosis. An increase in the dose of aspirin (especially if an in vitro aspirin effect is not shown at the lower dose) or use of ticlopidine should be tried if symptoms recur. Ticlopidine hydrochloride, a thienopyridine derivative, is another effective antiplatelet agent that has been

recently introduced into clinical practice. The recommended dosage is 250 mg twice a day. Its side effects are gastrointestinal symptoms, skin rash, and leukopenia, which require careful monitoring of clinical findings and blood tests during the first 3 months. Neither warfarin nor surgery is recommended in patients with slight to moderate stenosis. If the patient has a primary coagulopathy, polycythemia, or thrombocytosis, these disorders should be treated more specifically. ^

Prognosis and Future Perspectives. In patients with large artery occlusions, the risk of infarction is maximal in the days after occlusion. After the first week, the likelihood of further infarction is much less. Prognosis depends on whether the initial thrombus propagates distally or embolizes to intracranial arteries and the extent of collateral circulation that develops. Optimization of blood pressure and blood volume during the time when the collateral circulation is developing helps to augment blood flow to the penumbral zones and thus limits the extent of infarction. Of course, patients with large artery atherostenosis are at risk during the subsequent months and years of narrowing and occlusion of other arteries, so preventive measures instituted at the time of the initial symptoms may help in preventing or delaying further strokes. The effectiveness of surgery and angioplasty for various occlusive lesions is now under study in large trials. At times, thrombolysis and angioplasty may be used together because patients with thrombi superimposed on severe atherosclerotic occlusive disease often experience reocclusion of the artery after thrombolysis unless the atherostenosis is repaired. The optimal thrombolytic agent, portal of delivery, dose, timing, and target population for thrombolysis are now being studied. Many trials now are trying to define the usefulness of a variety of neuroprotective agents.

Was this article helpful?

0 0
Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook


Post a comment