Prevention and Facts
Whether you have had a stroke or have risk factors which put you at risk of stroke,
it is essential to do whatever possible to reduce that risk.
Here are answers to common questions about stroke and related diseases.
How common is stroke?
Stroke is the third leading cause of death in developed countries, after heart disease and cancer. For every 100,000 people in the US, 794 have had a stroke. Each year, 400,000 patients are discharged from hospitals after a stroke. Many of these patients will be left with disabilities, unable to resume their previous lifestyle or employment. This makes the social and economic impact of stroke one of the most devastating in medicine.
What causes an ischemic stroke?
Approximately 80 percent of all strokes are due to ischemic cerebral infarction, where brain tissue is injured because the blood supply is lost. 20 percent of strokes are due to bleeding into the brain because a blood vessel ruptures (hemorrhage). Cerebrovascular disease (disease of the blood vessels bringing blood to the brain) is caused by one of several processes involving the blood vessels of the brain:
- disease of the blood vessel, such as atherosclerosis, lipohyalinosis, inflammation, amyloid deposition, arterial dissection, developmental malformation, aneurysmal dilation, or venous thrombosis
- a clot ( embolus) from the heart or large vessels in the chest breaks off and lodges in an intracranial vessel
- low pressure/flow of blood to the brain or sluggish flow due to increased blood viscosity
Administering appropriate therapy in ischemic stroke is greatly aided by understanding why the stroke occurred. Typically, there is a suspicion of the cause when the patient first arrives and then confirmatory tests are done to prove the mechanism. Because there isn't a single cause of stroke, there isn't a single treatment. Each stroke is unique and the preventive strategies tailored to the needs of that individual patient.
How is a TIA different than a stroke?
The problems listed above can cause temporary neurological symptoms (a TIA or transient ischemic attack) or a permanent deficit (stroke or cerebral infarction). Low flow TIAs are usually short-lived (minutes). They are often recurrent. While they may occur as little as several times per year, they usually occur more often once per week up to several times per day. They are generally stereotyped, especially when they are due to hemodynamically significant stenotic lesions at the origin of the internal carotid artery or at the siphon portion of the internal carotid artery where collateral flow to the circle of Willis is inadequate. Symptoms usually include stereotyped hand, arm, leg, face, tongue or cheek numbness or weakness. Recurrent language, visual, or cognitive difficulty may also occur depending on the vascular territory involved.
When the stenotic lesion that obstructs flow involves the blood vessels in the back of the brain, the vertebral and the basilar arteries, the recurrent symptoms are often not stereotyped. There are many closely packed neuronal structures in the brainstem. Obstructive lesions in the distal vertebral artery or at the vertebrobasilar junction usually have disorganized dizziness that may or may not contain spinning or vertigo. It may seem that the room is tilting or the floor is coming up instead of spinning dizziness. Other symptoms may include numbness of one side of the body or face, dysarthria or diplopia. There may also be bilateral leg and arm weakness or numbness. There may be a feeling of all of low energy or a feeling of impending doom. Ischemia in the territory of the top of the basilar artery or proximal posterior cerebral artery may have all of the above recurrent symptoms as well as overwhelming drowsiness, vertical diplopia, eyelid drooping and inability to look up.
What is carotid disease? Can anything be done for it?
Atherosclerosis at the origin of the internal carotid artery, one of the three major extracranial vessels bringing blood to the brain, is an important cause of TIA's and stroke. The symptoms and pathological substrate of carotid artery atherosclerotic occlusive disease were first described by C. Miller Fisher in 1951. He related atherosclerotic disease at the carotid bifurcation to ischemic symptoms in the ipsilateral eye and brain. The modern era has seen an extraordinary expansion in our approach to the diagnosis and management of patients with carotid artery stenosis. A carotid bruit may be heard over the site of carotid stenosis. However, it is a poor predictor of underlying carotid stenosis with both poor sensitivity and specificity. Similarly, ocular bruits and abnormalities or asymmetries of facial pulses are not reliable predictors of carotid stenosis.
When there is 70 percent or greater narrowing of the lumen, the threat of embolic or low flow TIA or stroke is quite high. Data from the North American Symptomatic Carotid Endarterectomy trial (NASCET) suggests that even a 50 percent stenosis is important when considering a carotid endarterectomy if you have already had a symptom referable to that artery. Carotid endarterectomy is a surgical procedure to remove the plaque from the carotid artery. In the published studies, the complication rates range from 2.3% in the asymptomatic population to 6.7% in symptomatic patients. Higher complication rates, particularly in the asymptomatic patients, can nullify the benefit of surgery.
Intracranial atherothrombotic disease can produce low flow or embolic TIA. It occurs most commonly at the distal vertebral artery/vertebrobasilar junction/proximal basilar artery site. Superimposed thrombosis with thrombus propagation and embolism can result in a stroke. The siphon portion of the internal carotid artery and the middle cerebral artery stem are two other common sites of atherosclerosis. These lesions can be identified noninvasively with MR- angiography, duplex ultrasound and transcranial Doppler. These imaging modalities can also be used to follow patients and guide therapeutic decisions.
What other neurological entities mimic TIA/Stroke?
Glioblastoma and other intracranial tumors often present with transient focal neurological symptoms. The symptoms often span two different arterial territories, making a vascular lesion less likely. Focal neurological symptoms that are attributed to migraine with or without headache occur at all ages, but most often after the age of 60. Focal seizures from any cause may mimic TIAs. These most commonly arise from cavernous angioma, AVM, tumors, especially glioblastoma and old strokes. But idiopathic focal seizures do occur. They usually have positive symptoms including aura and/or shaking as opposed to weakness or sensory deficit. Rarely demyelinating lesions give rise to focal transient symptoms but they generally last for at least several days. Arteritides, other than temporal arteritis (TA), are rare. TA can cause transient monocular blindness. A sedimentation rate will suggest the diagnosis and should be obtained whenever transient monocular visual symptoms occur. Arteriovenous malformation and cavernous angioma usually produce transient focal symptoms by causing focal seizures. On occasion, arteriovenous malformations are large enough to produce transient focal symptoms on the basis of a "steal" phenomenon, where the AVM shunts blood away from normal tissue.
What are stroke risk factors?
Treatable risk factors for atherosclerosis include hypertension, diabetes, tobacco use, hypercholesterolemia, sedentary lifestyle. Modification of these risk factors is important in the primary and secondary prevention of cardiac disease and reduces the risk of atherosclerotic ischemic stroke. Click on the individual risk factors to learn more.
There are some risk factors which are technically non-modifiable. Risk of stroke is most strongly associated with age. The older you are, the greater the risk of stroke. Although we cannot alter the aging process, we are learning more about what changes with age that might directly impact on stroke risk. Elucidating the actual pathophysiology may lead to interventions which can modify that risk. One example of this is the finding that older individuals have a more active prothrombotic system. Devising a means of safely reducing activation of prothombin may reduce stroke risk.
Similarly, male sex is a risk for stroke, despite the fact that overall women carry most of the burden of stroke due to their longevity. Hormonal factors clearly play a role, and estrogen is a likely candidate with its beneficial effects on endothelium and lipids. Women are at greatest risk of stroke in the post-menopausal stage of life. There are ongoing studies looking at the impact of hormone replacement therapy as a strategy for stroke risk reduction in women.
High blood pressure
Hypertension is the single most important treatable risk factor for stroke. Sixty percent of strokes in men and women and of all ages are attributed to hypertension. Both systolic and diastolic hypertension are independent risk factors for stroke. The Systolic Hypertension in the Elderly Program study demonstrated that in patients over 60 years of age with isolated systolic hypertension, treatment producing a mean reduction in systolic pressure from 155 mmHg to 143 mmHg led to a 36% reduction in stroke incidence over 4.5 years of followup.1 Meta-analysis of treatment trials of blood pressure reduction demonstrated a reduction in stroke incidence, with an average blood pressure reduction of 5.8 mmHg producing with a reduction in stroke incidence of 42% over a 2-5 year followup period.2 Hypertension, hyperlipidemia, and smoking are well-established risk factors for the development of carotid atherosclerosis. Hypertension promotes formation of the atherosclerotic lesions at the bifurcation of the common carotid artery. Diabetes and Black race are also independent risk factors for carotid bifurcation atherosclerosis, especially when hypertension and hyperlipidemia are co-existent.
Management of blood pressure and diabetes are important aspects of stroke prevention (click on risk factors for individual management).
Hyperlipidemia may be managed with diet modification alone, or with a combination of diet and lipid-lowering medical therapy. HMG-coA- reductase inhibitors have recently been approved for primary prevention of stroke in patients with coronary artery disease. Diet and cholesterol lowering therapy have been found to reduce the rate of stroke in patients with elevated and normal cholesterol. Apoprotein E genotypes are also predictors of atherothrombotic stroke.
Cigarette smoking is associated with approximately 50 percent increased risk for all stroke subtypes and has a strong, dose-response relationship for both ischemic stroke and subarachnoid hemorrhage. There is a dose effect- the more you smoke, the greater the risk. In both the Framingham Heart Study and the Nurses' Health Study, the risk of stroke in former cigarette smokers fell within 1-2 years of smoking cessation. After 5 years, the risk of stroke was similar to persons who had never smoked. In a meta-analysis of smoking and stroke, however, patients who had ever smoked, even if they had quit, retained a baseline risk higher than that of non-smokers. New therapies, such as sustained release bupropion, alone, or in combination with a nictine patch, may help people quit cigarettes. Passive smoke also appears to be a risk factor. Patients who spouses smoke had almost twice the risk of stroke, whether or not they were smokers themselves.
Diabetics have about twice the risk of ischemic stroke as compared to the general population. The benefits of aggressive treatment of diabetes has not been demonstrated for stroke prevention related to large vessel disease, but is recommended to prevent microvascular complications of diabetes.
The connection of obesity/weight-increase in adult years to stroke is not easily distinguished . Obesity is highly related to many major risk elements, such as hypertension, diabetes, and dyslipidemia. The studies which show the exact brunt of obesity to stroke have differed. In men, conclusions from the Physicians’ Health Study show that an increasing BMI is related with an increase in ischemic stroke, independently of the effects of hypertension, diabetes, and cholesterol. In women, the conclusions are not consistent - some of the inconsistent results show some positive, while others with no correlation.
Exercise, as little as brisk walking 30 minutes a day, reduces risk of stroke. Studies have consistently demonstrated that lack of exercise is a risk factor for stroke, and that any exercise is beneficial. The form of the exercise is irrelevant. The mechanism of action may be multifactorial: weight reduction, improved cardiovascular status, increased fibrinolytic activity.
Family History of Stroke
If you parents had coronary artery disease or stroke, you are at increased risk of stroke. The association does is weaker for siblings. There are many new candidate polymorphisms for pro-atherosclerotic and prothrombotic genes which may play a role in familial stroke risk. This remains a complicated, polygenetic disorder, however. The true risk is probably a combination of genetic predisposition and environmental factors.
There is no evidence that reducing homocysteine levels will lead to a reduction of stroke occurrence. Although there is no proven clinical benefit to high-dose vitamin therapy for mild to moderate hyperhomocysteinemia, patients should be encouraged to take a daily standard multivitamin preparation, given the low
risk and cost associated with vitamin therapy. Additional research is needed to determine whether there are subgroups that might benefit from more aggressive vitamin therapy, particularly over the long term.
The association between
APL antibodies and stroke is strongest for young adults (<50 years of age). APL antibodies were detected in 40.7% of stroke patients, but they had no significant effect on the risk of stroke recurrence.
Low Vitamin B6, B12, folate
Diets rich in fruit an vegetables, particularly vegetables, help reduce risk of stroke. For every 3 servings of fruit and vegetables incorporated into the daily diet, there is a 22% reduction in stroke risk. Diets rich in fruit and vegetables and low in fat are ideal. There are many potential mechanisms for how this works. Weight reduction, improved levels of vitamins ( especially those involved in homocysteine metabolism), better glycemic control, lower cholesterol may all be factors.
Antioxidant vitamins may help prevent progression of atherosclerotic plaques in the internal carotid artery. Vitamins E, C, and beta-carotene may help prevent oxidation of LDL, thereby preventing incorporation of the oxidized LDL into macrophages, the "foam cells" of athersclerotic plaques. Diets rich in fruits and vegetables can reduce the risk of stroke-eating 3 servings a day can reduce risk by 22%. These foods also contain folate, B-vitamins, and vitamin K, which all appear to have beneficial effects for stroke prevention. Fish oils, (w-3 fatty acids) are believed to lower triglycerides and very low density lipoproteins. They may also reduces serum viscosity by lowering fibrinogen. While they may be effective in reducing cardiovascular disease, they have the potential to have adverse effects on total cholesterol, LDL, and HDL, and therefore must be closely monitored.
Folate and B6 supplementation is of value in reducing homocysteine in patients with homocysteinemia, but a clinical trial assessing the efficacy of supplementation in patients with elevated homocysteine levels is still ongoing.
Carotid artery stenosis
Carotid atherosclerosis is usually the most severe within 2 cm of the bifurcation, and predominantly involves the posterior wall of the vessel. The plaque encroaches on the lumen of the internal carotid artery and often extends caudally into the common carotid artery. An hourglass configuration to the stenosis is typical with time. Thrombus can become superimposed on the atheroma. Thus, the mechanism of stroke may be embolism of the thrombotic material, or low-flow due to the stenosis with inadequate collateral compensation.
When the internal carotid artery occludes completely, it can also cause low flow or embolic ischemic events depending on the adequacy of collateral flow through the orbit and across the circle of Willis. The greatest risk of low flow TIA or stroke is at the time of occlusion and risk diminishes after the first year. There is a phenomenon of delayed stroke, occurring many months after carotid occlusion, presumably on the basis of propagation of thrombus or embolism from the distal portion of the clot. The apparent diagnosis of carotid occlusion by CDUS or MRA in a symptomatic patient is a special clinical problem. Both MRA and CDUS have false positive error rates of 0 - 20%.Therefore, followup CT-angiography is usually required to exclude the diagnosis of high grade carotid stenosis in symptomatic patients. In some patients, a conventional angiogram may still be warranted if the issue is not resolved. In asymptomatic patients, in whom the risk of stroke is comparatively low, the risk of confirmatory angiography may not be warranted.
The North American Symptomatic Carotid Endarterectomy Trial (NASCET) studied patients with a 30 to 99% carotid artery stenosis who had had recent ipsilateral cerebral ischemia, TIA or minor stroke within the previous 120 days, were randomized to CEA and medical treatment or to medical treatment alone. The trial was stopped early by the safety and monitoring committee for patients with > 70% stenosis when interim results showed that patients with high-grade stenosis benefited significantly from CEA, with a cumulative ipsilateral stroke rate at 2 years of 9% as compared with 26% for those on medical therapy alone. CEA did not benefit patients with a < 30% stenosis. Patients with a 50-69% stenosis had modest benefit from CEA, but with stenoses > 70% stenosis clearly benefited from surgery. The risk of stroke and the benefit from surgery increased with the degree of stenosis. The surgical morbidity and mortality did not vary significantly for patients with varying degrees of stenosis.
Patients with transient monocular blindness (amaurosis fugax) had a lower 2 year incidence of ipsilateral stroke of 17% compared with a 44% incidence in those with transient cerebral ischemia (TIA). In addition, patients with symptoms within 6 months had a higher stroke risk compared to those who were symptom-free for 12 to 18 months.
The Asymptomatic Carotid Atherosclerosis Study randomized asymptomatic patients with >60% stenosis to CEA and medical therapy or medical therapy alone. 11 High-grade carotid stenosis was defined by either duplex ultrasound plus oculoplethysmography, or angiography. All surgical patients underwent angiography prior to CEA. The primary outcome event (any perioperative stroke or death or any subsequent ipsilateral stroke or stroke death) at 5 years in the surgical group was 4.8% versus 10.6% in the medical group - an absolute risk reduction of 5.8%. A benefit from CEA was demonstrated for men, but not women. The perioperative stroke and death risk was 2.3%. Had the complication rates been higher, there would not have been a benefit to surgery. This is important to consider in the generalization of the results to centers performing CEA outside the tight regulation of a clinical trial. The ACAS study stands alone in failing to demonstrate an increased stroke risk with higher degrees of stenosis.
There is increasing interest in the use of angioplasty and stents for the treatment of carotid artery stenosis. These techniques have been applied to symptomatic patients who are believed to be high risk surgical candidates or who refuse surgery. While the preliminary data are encouraging, the techniques have not been standardized and are at the preliminary research stage. The procedure must be performed by an experienced invasive radiologist, neuroradiologist or cardiologist with appropriate surgical backup. Randomized clinical trials comparing CEA to stenting are currently underway.
Thus, medical management of carotid stenosis without surgical intervention is appropriate (1) the patient is symptomatic and has a > 50% stenosis, (2) the patient is asymptomatic and has a > 60% stenosis, or (3) is deemed to be at high risk of complications from surgery despite having "surgical" disease. Medical management of atherosclerotic risk factors is important even in patients who have undergone carotid endarterectomy to reduce the risk of recurrent stenosis and reduce the risk of cardiac events, a common co-morbidity in cerebrovascular disease patients.
Both persistent AF and paroxysmal AF are potent predictors of first and recurrent stroke. More than 75 000 cases of stroke per year are attributed to AF. It has been estimated that AF affects > 2 000 000 Americans and becomes more frequent Sacco et al Guidelines for Prevention of Stroke in Patients With IS or TIA 587 with age, ranking as the leading cardiac arrhythmia in the elderly. Data from the AF clinical trials show that age, recent congestive heart failure, hypertension, diabetes, and prior thromboembolism have been found to identify high-risk groups for arterial thromboembolism among patients with AF.
Aspirin, the most commonly used antiplatelet agent, inhibits the enzyme cyclo-oxygenase reducing production of thromboxane A2, a stimulator of platelet aggregation. This interferes with thrombus formation and thereby reduces the risk of stroke. In high risk patients, there was a 31% risk reduction in nonfatal stroke. For cerebrovascular patients alone, antiplatelet therapy reduced risk of secondary stroke, MI and vascular death by 22%.
The dose of aspirin ranges between 20-1300mg in various clinical trials. The complications of aspirin increase with higher doses. The studies have not shown any evidence that higher doses of aspirin convey greater benefit. Thus the recommendations are for low dose, 50-325mg of aspirin a day.
Ticlopidine, a newer antiplatelet agent, inhibits ADP dependent fibrinogen binding. Ticlopidine has a relative risk reduction of 21% in stroke, MI, and vascular death. The common side effects of ticlopidine include rash and diarrhea. Cholestatic jaundice has occurred in a small number of patients. A rare, but serious complication of ticlopidine therapy is neutropenia which occurred in approximately 1% of patients. Thus, for the first three months of treatment, patients must undergo biweekly CBCs. Because of these complications, the relatively modest increase in efficacy of ticlopidine over aspirin, and its relatively high cost, ticlopidine is generally not considered a first line antiplatelet agent for stroke prevention but may be useful in patients who cannot tolerate aspirin.
Clopidogrel is a newer antiplatelet agent similar to ticlopidine in mechanism of action. The Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial compared outcome events of stroke, MI, and vascular death in 19,185 patients treated with aspirin (325 mg) or clopidogrel (75 mg) who had had a recent stroke, MI or symptomatic peripheral arterial disease. There was a relative risk reduction of 8.7% in clopidogrel treated patients. Clopidogrel does not appear to cause neutropenia.
Dipyridamole impairs platelet function by inhibiting phosphodiesterase. The recently published second European Stroke Prevention Study (ESPS-2) randomized 6602 patients who had experienced a recent transient ischemic attack or ischemic stroke to four treatment groups: 25 mg aspirin + 200 mg dipyridamole, 200 mg dipyridamole, 25 mg aspirin, and placebo, each given twice daily. 20 Dipyridamole was given as Persantin® Retard 200 mg, a sustained release tablet. In contrast to previous studies, both dipyridamole monotherapy and aspirin monotherapy had an independent and significant effect in preventing the recurrence of stroke with relative risk reductions of 16% and 18% respectively. The combination of dipyridamole plus aspirin was additive, producing a 37% relative risk reduction in stroke compared to placebo and a 23% relative risk reduction over aspirin alone.
Coumadin warfarin is infrequently used in patients with carotid stenosis. For very severe stenoses, particularly in patients awaiting carotid endarterectomy, coumadin is sometimes used to maintain the patency of the lumen. Coumadin is also used in cases of carotid occlusion. Patients are often kept anticoagulated for 3-6 months to prevent propagation of thrombus in the internal carotid artery. Neither of these are proven indications for warfarin therapy. A large, multicenter, randomized, double-blind study comparing the efficacy of warfarin (INR 1.4-2.8) versus aspirin (325 mg/d) has been completed. For more on this study, click here.
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