Recommendation grades (Class I - III) and levels of evidence (A-C) are defined at the end of the "Major Recommendations" field.
Summary
Assessing the Risk of a First Stroke
Each individual patient should have an assessment of his or her stroke risk (Class I, Level of Evidence A). The use of a risk-assessment tool such as the Framingham Stroke Profile should be considered as these tools can help identify individuals who could benefit from therapeutic interventions and who may not be treated based on any 1 risk factor (Class IIa, Level of Evidence B).
Genetic Causes of Stroke
Referral for genetic counseling may be considered for patients with rare genetic causes of stroke (Class IIb, Level of Evidence C). There remain insufficient data to recommend genetic screening for the prevention of a first stroke.
Cardiovascular Disease
Persons with evidence of noncerebrovascular atherosclerotic vascular disease (coronary heart disease, cardiac failure, or intermittent claudication) are at increased risk of a first stroke.
Treatments used in the management of these other conditions (e.g., platelet antiaggregants) and as recommended in other sections of this guideline can reduce the risk of stroke (Class and Level of Evidence as indicated in the relevant sections).
Hypertension
Regular screening for hypertension (at least every 2 years in adults and more frequently in minority populations and the elderly) and appropriate management (Class I, Level of Evidence A), including dietary changes, lifestyle modification, and pharmacological therapy as summarized in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) (Chobanian et al., 2003), are recommended.
Cigarette Smoking
Abstention from cigarette smoking and smoking cessation for current smokers are recommended (see Table below titled "Other Guideline Recommendations") (Class I, Level of Evidence B). Data from cohort and epidemiological studies are consistent and overwhelming. Avoidance of environmental tobacco smoke for stroke prevention should also be considered (Class IIa, Level of Evidence C). The use of counseling, nicotine products, and oral smoking-cessation medications has been found to be effective for smokers and should be considered (Class IIa, Level of Evidence B).
Diabetes
It is recommended that hypertension be tightly controlled in patients with either type 1 or type 2 diabetes (the JNC 7 recommendation of <130/80 mm Hg in diabetic patients is endorsed) as part of a comprehensive risk-reduction program (Class I, Level of Evidence A). Treatment of adults with diabetes, especially those with additional risk factors, with a statin to lower the risk of a first stroke is recommended (Class I, Level of Evidence A) ("Executive Summary of the Third Report," 2001). Recommendations to consider treatment of diabetic patients with an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) are endorsed.
Atrial Fibrillation
Anticoagulation of patients with atrial fibrillation who have valvular heart disease (particularly those with mechanical heart valves) is recommended (Class I, Level of Evidence A).
Antithrombotic therapy (warfarin or aspirin) is recommended to prevent stroke in patients with nonvalvular atrial fibrillation based on assessment of their absolute stroke risk and estimated bleeding risk while considering patient preferences and access to high-quality anticoagulation monitoring (Class I, Level of Evidence A). Warfarin (international normalized ratio [INR] 2.0 to 3.0) is recommended for high-risk (>4% annual risk of stroke) patients (and for most moderate-risk patients according to patient preferences) with atrial fibrillation who have no clinically significant contraindications to oral anticoagulants (Class I, Level of Evidence A).
Other Cardiac Conditions
Various American Heart Association (AHA) and American College of Cardiology practice guidelines recommend strategies to reduce the risk of stroke in patients with a variety of cardiac conditions. These include the management of patients with valvular heart disease (Cannegieter, Rosendaal, & Briet, 1994), unstable angina (Braunwald et al., 2002), chronic stable angina (Gibbons et al., 2003), and acute myocardial infarction (MI) (Antman et al., 2004). Strategies to prevent postoperative neurological injury and stroke in patients undergoing surgical revascularization for atherosclerotic heart disease are discussed in detail in the recently published coronary artery bypass graft surgery guidelines (Eagle et al., 2004). It is reasonable to prescribe warfarin for post-ST-segment– elevation patients with MI and left ventricular (LV) dysfunction with extensive regional wall-motion abnormalities (Class IIa, Level of Evidence A), and warfarin may be considered in patients with severe left ventricular (LV) dysfunction with or without congestive heart failure (Class IIb, Level of Evidence C) (Antman et al., 2004).
Dyslipidemia
National Cholesterol Education Program III guidelines for the management of patients who have not had a cerebrovascular event with elevated total cholesterol, or with elevated non-high-density lipoprotein (HDL) cholesterol in the presence of hypertriglyceridemia, are endorsed (National Institutes of Health, 2002; Grundy et al., 2004). It is recommended that patients with known coronary heart disease (CHD) and high-risk hypertensive patients even with normal low-density lipoprotein (LDL) cholesterol levels be treated with lifestyle measures and a statin (Class I, Level of Evidence A). The use of lipid-lowering therapy in diabetic patients is specifically addressed in the diabetes section of this guideline.
Suggested treatments for patients with known CHD and low HDL cholesterol include weight loss, increased physical activity, smoking cessation, and possibly niacin or gemfibrozil (Class IIa, Level of Evidence B).
Asymptomatic Carotid Stenosis
It is recommended that patients with asymptomatic carotid artery stenosis be screened for other treatable causes of stroke and that intensive therapy of all identified stroke risk factors be pursued (Class I, Level of Evidence C). The use of aspirin is recommended unless contraindicated because aspirin was used in all of the cited trials as an antiplatelet drug except in the surgical arm of 1 study, in which there was a higher rate of MI in those who were not given aspirin (Class I, Level of Evidence B). Prophylactic carotid endarterectomy is recommended in highly selected patients with high-grade asymptomatic carotid stenosis performed by surgeons with <3% morbidity/mortality rates (Class I, Level of Evidence A). Patient selection should be guided by an assessment of comorbid conditions and life expectancy, as well as other individual factors, and be balanced by an understanding of the overall impact of the procedure if all-cause mortality is considered as one of the end points, and it should include a thorough discussion of the risks and benefits of the procedure with an understanding of patient preferences. Carotid angioplasty–stenting might be a reasonable alternative to endarterectomy in asymptomatic patients at high risk for the surgical procedure (Class IIb, Level of Evidence B); however, given the reported periprocedural and overall 1-year event rates, it remains uncertain whether this group of patients should have either procedure.
Sickle Cell Disease (SCD)
It is recommended that children with SCD be screened with transcranial Doppler (TCD) ultrasound starting at 2 years of age (Class I, Level of Evidence B). It is recommended that transfusion therapy be considered for those at elevated stroke risk (Class I, Level of Evidence B). Although the optimal screening interval has not been established, it is reasonable that younger children and those with TCD velocities in the conditional range should be rescreened more frequently to detect development of high-risk TCD indications for intervention (Class IIa, Level of Evidence B). Pending further studies, it is reasonable to continue transfusion even in those whose TCD velocities revert to normal (Class IIa, Level of Evidence B). Magnetic resonance imaging and magnetic resonance angiography criteria for selection of children for primary stroke prevention using transfusion have not been established, and these tests should not be substituted for TCD (Class III, Level of Evidence B). Adults with SCD should be evaluated for known stroke risk factors and managed according to the general guidelines in this statement (Class I, Level of Evidence A).
Postmenopausal Hormone Therapy
It is recommended that postmenopausal hormone therapy (with estrogen with or without a progestin) not be used for primary prevention of stroke (Class III, Level of Evidence A) (National Institutes of Health, 2002; Grundy et al., 2004). The use of hormone replacement therapy for other indications should be informed by the risk estimate for vascular outcomes provided by the reviewed clinical trials. There are not sufficient data to provide recommendations about the use of other forms of therapy such as selective estrogen receptor modulators.
Diet and Nutrition
A reduced intake of sodium and increased intake of potassium is recommended to lower blood pressure in persons with hypertension (Class I, Level of Evidence A), which may thereby reduce the risk of stroke. The recommended sodium intake is <2.3 g/day (100 mmol/day), and the recommended potassium intake is >4.7 g/day (120 mmol/day). The Dietary Approaches to Stop Hypertension (DASH) diet, which emphasizes fruit, vegetables, and low-fat dairy products and is reduced in saturated and total fat, also lowers blood pressure and is recommended (Class I, Level of Evidence A). A diet that is rich in fruits and vegetables may lower the risk of stroke and may be considered (Class IIb, Level of Evidence C).
Physical Inactivity
Increased physical activity is recommended because it is associated with a reduction in the risk of stroke (Class I, Level of Evidence B). Exercise guidelines as recommended by the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (>30 minutes of moderate intensity activity daily) as part of a healthy lifestyle are reasonable (Class IIa, Level of Evidence B).
Obesity and Body Fat Distribution
Epidemiological studies indicate that increased body weight and abdominal fat are directly associated with stroke risk. Weight reduction is recommended because it lowers blood pressure (Class I, Level of Evidence A) and may thereby reduce the risk of stroke.
Metabolic Syndrome
Management of individual components of the metabolic syndrome, including lifestyle measures and pharmacotherapy as recommended in the National Cholesterol Education Program Adult Treatment Panel III ("Executive Summary of the Third Report, 2001) and the JNC 7 (Chobanian et al., 2003) as reviewed in other sections of this guideline, are endorsed.
Lifestyle management should include exercise, appropriate weight loss, and proper diet. Pharmacotherapy may include medications for blood pressure lowering, lipid lowering, glycemic control, treatment of microalbuminuria or proteinuria, and antiplatelet therapy (e.g., aspirin) according to the individual circumstance and risk. It is not known whether agents that ameliorate aspects of the insulin resistance syndrome are useful for reducing stroke risk.
Alcohol Abuse
Reduction of alcohol consumption in heavy drinkers through established screening and counseling methods as outlined in the US Preventive Services Task Force Update 2004 is endorsed (US Preventive Services Task Force [USPSTF], 2004). For those who consume alcohol, a recommendation of <2 drinks per day for men and <1 drink per day for nonpregnant women best reflects the state of the science for alcohol and stroke risk (US Department of Health and Human Service, 2005) (Class IIb, Level of Evidence B).
Drug Abuse
Successful identification and management of drug abuse can be challenging. When a patient is identified as having a drug addiction problem, referral for appropriate counseling may be considered (Class IIb, Level of Evidence C).
Oral Contraceptives (OCs)
The incremental risk of stroke associated with use of low-dose OCs in women without additional risk factors appears low, if it exists (Class III, Level of Evidence B) (Chan et al., 2004; Siritho et al., 2003). It is suggested that OCs be discouraged in women with additional risk factors (e.g., cigarette smoking or prior thromboembolic events [Class III, Level of Evidence C]) (Chan et al., 2004; Bousser et al., 2000). For those who elect to assume the increased risk, aggressive therapy of stroke risk factors may be useful (Class IIb, Level of Evidence C) (Chan et al., 2004; Siritho et al., 2003; Bousser et al., 2000).
Sleep-Disordered Breathing (SDB)
SDB is associated with stroke risk. Questioning bed partners and patients, particularly those with abdominal obesity and hypertension, about symptoms of SDB and referral to a sleep specialist for further evaluation as appropriate may be useful, especially in the setting of drug-resistant hypertension (Class IIb, Level of Evidence C).
Migraine
There are insufficient data to recommend a specific treatment approach that would reduce the risk of first stroke in women with migraine, including migraine with aura.
Hyperhomocysteinemia
Recommendations to meet current guidelines for daily intake of folate (400 microg/day), B6 (1.7 mg/day), and B12 (2.4 microg/day) by consumption of vegetables, fruits, legumes, meats, fish, and fortified grains and cereals (for nonpregnant, nonlactating individuals) may be useful in reducing the risk of stroke (Class IIb, Level of Evidence C). There are insufficient data to recommend a specific treatment approach that would reduce the risk of first stroke in patients with elevated homocysteine levels. In the interim, use of folic acid and B vitamins in patients with known elevated homocysteine levels may be useful given their safety and low cost (Class IIb, Level of Evidence C).
Elevated Lipoprotein(a)
Although no definitive recommendations about lipoprotein(a) (Lp(a)) modification can be made because of an absence of outcome studies showing clinical benefit, treatment with niacin (extended-release or immediate-release formulation at a total daily dose of 2000 mg/day as tolerated) can be considered because it reduces Lp(a) levels by approximately 25% (Class IIb, Level of Evidence C). Further recommendations must await the results of prospective trials utilizing niacin and statins in subjects stratified for Lp(a) concentration and apo(a) isoform subtypes (Guyton et al., 1998).
Elevated Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
No recommendations about Lp-PLA2 modification can be made because of an absence of outcome studies showing clinical benefit with reduction in its blood levels.
Hypercoagulability
There are insufficient data to support specific recommendations for primary stroke prevention in patients with a hereditary or acquired thrombophilia.
Inflammation
Currently, no evidence supports the use of hs-C-reactive protein (CRP) screening of the entire adult population as a marker of general vascular risk. Aggressive risk factor modification is recommended for patients at high risk for stroke given exposure to traditional risk factors regardless of hs-CRP level. In agreement with AHA/CDC guidelines, hs-CRP can be useful in considering the intensity of risk factor modification in those at moderate general cardiovascular risk on the basis of traditional risk factors (Class IIa, Level of Evidence B) (Adams et al., 1998).
Infection
Data are insufficient to recommend antibiotic therapy for stroke prevention on the basis of seropositivity for 1 or a combination of putative pathogenic organisms. Future studies on stroke risk reduction based on treatment of infectious diseases will require careful stratification and identification of patients at risk for organism exposure.
Aspirin
Aspirin is not recommended for the prevention of a first stroke in men (Class III, Level of Evidence A). The use of aspirin is recommended for cardiovascular (including but not specific to stroke) prophylaxis among persons whose risk is sufficiently high for the benefits to outweigh the risks associated with treatment (a 10-year risk of cardiovascular events of 6% to 10%) (Class I, Level of Evidence A). Aspirin can be useful for prevention of a first stroke among women whose risk is sufficiently high for the benefits to outweigh the risks associated with treatment (Class IIa, Level of Evidence B). The use of aspirin for other specific situations (e.g., atrial fibrillation, carotid artery stenosis) is discussed in the relevant sections of this statement.
Other Guideline Recommendations
| Factor |
Goal |
Recommendations |
| Cigarette smoking (USPSTF, 1996) |
Cessation
Avoid environmental tobacco smoke
|
Strongly encourage patient and family to stop smoking. Provide counseling, nicotine replacement, and formal programs as available. |
| Diabetes |
Improved glucose control
Treatment of hypertension
Consider statin
|
Improve glucose control through diet, oral hypoglycemics, and insulin. See guidelines and policy statements. |
| Asymptomatic carotid stenosis |
|
Endarterectomy may be considered in selected patients with >60% and <100% carotid stenosis, performed by surgeon with surgical morbidity/mortality rate <3%. Careful patient selection should be guided by comorbid conditions, life expectancy, patient preference, and other individual factors. Patients with asymptomatic stenosis should be fully evaluated for other treatable causes of stroke. |
| Sickle cell disease |
Monitor children with SCD with transcranial Doppler for development of vasculopathy (see text) |
Institute transfusion therapy for children who develop evidence of sickle cell vasculopathy (see text). |
| Physical activity (Pate et al., 1995) |
At least 30 minutes of moderate-intensity activity daily |
Encourage moderate exercise (e.g., brisk walking, jogging, cycling, or other aerobic activity).
Incorporate medically supervised programs for high-risk patients (e.g., cardiac disease) and adaptive programs according to physical/neurological deficits.
|
| Poor diet/nutrition |
Well-balanced diet |
A diet containing >5 servings of fruits and vegetables per day may reduce the risk of stroke. |
| Alcohol (USPSTF, 1996) |
Moderation |
Men should consume no more than 2 drinks/day, and nonpregnant women should consume no more than 1 drink/day. |
| Drug abuse (USPSTF, 1996) |
Cessation |
An in-depth history of substance abuse should be included as part of a complete health evaluation for all patients. |
| Oral contraceptive use |
Avoid in those at high risk |
Inform patients about stroke risk and encourage alternative forms of birth control among women who smoke cigarettes, have migraines (especially with older age or smoking), are >35 years of age, or have had prior thromboembolic events. |
| Sleep-disordered breathing |
Successful treatment of sleep-disordered breathing |
Consider sleep laboratory evaluation in patients with snoring, excessive sleepiness, and vascular risk factors, particularly if body mass index is >30 and drug-resistant hypertension is present. |
Definitions:
Levels of Evidence
Level of Evidence A: Data derived from multiple randomized clinical trials.
Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies.
Level of Evidence C: Consensus opinion of experts.
Strength of Recommendations
Class I Conditions for which there is evidence for and/or general agreement that the procedure or treatment is useful and effective.
Class II Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.
Class IIa The weight of evidence or opinion is in favor of the procedure or treatment.
Class IIb Usefulness/efficacy is less well established by evidence or opinion.
Class III Conditions for which there is evidence and/or general agreement that the procedure or treatment is not useful/effective and in some cases may be harmful.
