The latest edition of the AHA/ASA (American Heart Association/American Stroke Association) guidelines for primary stroke prevention was recently published in the journal Stroke and is intended to provide extensive and timely evidence-based recommendations for effective first-time stroke prevention. This article will address each of these evidence-based recommendations, as follows.
In the United States, nearly 795,000 people suffer a stroke each year, of which approximately 60,000 are first-time episodes. Stroke is currently ranked as the fourth leading cause of death in the United States. Globally, the incidence of stroke has decreased by 42% in high-income countries over the past 40 years, but has increased by more than 100% in low- and middle-income countries. Today, the incidence of stroke in low- and middle-income countries is much higher than in developed countries.
In addition, stroke is a major cause of functional impairment, which not only changes the life of the patient, but also the lives of family members and caregivers. Although patients with acute ischemic stroke can be treated with reperfusion therapy, for example, effective preventive measures are still the best way to reduce the burden of stroke. Given that more than 76% of strokes are first-episode, primary prevention of stroke is particularly important. Therefore, this article summarizes the identified and newly discovered stroke risk factors and categorizes and elaborates on the evidence-based recommendations.
I. Assessment of first stroke risk (recommendations)
The use of stroke risk assessment tools, such as the AHA/ACC CV risk calculator, is reasonable; as these tools help to identify patients who can benefit from therapeutic interventions and those who cannot be treated with a single risk factor. These calculation tools, can alert clinicians and patients to possible risks, but treatment decisions need to be made with the overall patient risk in mind. (Class IIa recommendation; Level of Evidence B)
II. Non-interventional risk factors (age, sex, low birth weight, race, genetic factors) – Recommendations
1. Ask for family history to help identify patients at increased risk of stroke; (Class IIa recommendation; Level of evidence Class A)
2. Consider recommending genetic counseling for stroke patients with rare genetic causes; (Class IIb recommendation; Level of evidence Class C)
3. Enzyme replacement therapy may be considered for Fabry disease, but it has not been shown to reduce stroke risk and the effect is unknown; (Class IIb recommendation; Level C)
4. Non-invasive screening for unruptured intracranial aneurysms is reasonable in patients with more than 2 first-degree relatives with subarachnoid hemorrhage (SAH) or intracranial aneurysm (Class IIb recommendation; Level C)
5. Non-invasive screening for unruptured intracranial aneurysms should be considered in patients with AKDPD who have more than 1 relative with autosomal dominant polycystic kidney disease (AKDPD) with SAH or more than 1 relative with AKDPD with intracranial aneurysm; (Class IIb recommendation; Level C of the evidence)
6. Non-invasive screening for unruptured intracranial aneurysms may be considered in patients with fibromuscular dysplasia of the neck; (Class IIb recommendation; Level C of the evidence)
7. Pharmacologic dosing of vitamin K antagonists should be considered when initiating therapy; (Class IIb recommendation, Level C of the evidence)
8. Noninvasive screening for unruptured intracranial aneurysms is not recommended in patients with no more than 1 relative with SAH or intracranial aneurysm; (Class III recommendation; Level C of the evidence)
9. Non-invasive screening for unruptured intracranial aneurysms is not recommended for carriers of autosomal dominant polycystic kidney disease or Ehlers-Danlos type IV mutation; (Class III recommendation; Level C of the evidence)
10. Genetic screening for first stroke prevention is not recommended in the general population; (Class III recommendation; Level C of the evidence)
11. Genetic screening for risk of myopathy is not recommended when statin therapy is considered; (Class III recommendation; Level C of the evidence)
III. Well-documented risk factors that can be intervened (recommendations)
(i) Lack of physical activity.
1. Physical activity is recommended because it is associated with a reduced risk of stroke; (Class I recommendation; Level of Evidence B)
2. Healthy adults should engage in moderate/high intensity aerobic exercise for at least 40 minutes at least 3-4 times per week (Class I recommendation; Level B of the evidence)
(ii) Dyslipidemia.
1. The 2013 ACC/AHA Guidelines for Controlling Blood Cholesterol to Reduce the Risk of Atherosclerotic Cardiovascular Disease (ASCVD) in Adults mentions that for patients with a 10-year risk of cardiovascular events, in addition to lifestyle changes, HMG coenzyme A reductase inhibitors (statins) are recommended for primary prevention of ischemic stroke; (Class I recommendation; Level of Evidence A)
2. Niacin therapy may be considered for patients with reduced high-density lipoprotein (HDL) cholesterol or elevated lipoprotein(a), but its effectiveness in preventing ischemic stroke in these patients is not known. Niacin can increase the risk of myopathy and should be used with caution; (Class IIb recommendation; Level of Evidence B)
3. Fibrate derivatives may be considered for the treatment of patients with hypertriglyceridemia, but their efficacy in preventing ischemic stroke is not known; (Class IIb recommendation; Level of evidence Class C)
4. Lipid-lowering therapies other than statins, such as fibrate derivatives, bile acid chelators, niacin, and ezetimibe, may be considered for patients who cannot tolerate statins, but their effectiveness in preventing stroke has not been demonstrated; (Class IIb recommendation; Level C of the evidence)
(iii) Diet and nutrition.
1. As recommended in the American Dietary Guidelines, sodium intake should be reduced and potassium intake increased to lower blood pressure (Class I recommendation; Level A of the evidence)
2. A DASH diet (emphasizing fruit, vegetables, and low-fat dairy products, and reducing saturated fatty acids) is recommended to reduce blood pressure (Class I recommendation; Level A of the evidence)
3. A diet rich in fruits and vegetables is beneficial (increased intake of potassium) and has the potential to reduce stroke risk; (Class I recommendation; Level B of the evidence)
4. A Mediterranean diet rich in nuts is likely to reduce the risk of stroke; (Class IIa recommendation; Level B of the evidence)
(iv) Hypertension.
1. Routine screening for blood pressure and appropriate treatment of hypertensive patients through lifestyle changes and pharmacotherapy are recommended; (Class I recommendation; Level A of the evidence)
2. Annual screening for hypertension and promotion of a healthy lifestyle are recommended for patients with pre-hypertension (systolic blood pressure 120-139 mmHg/diastolic blood pressure 80-89 mmHg); (Class I recommendation; Level A of the evidence)
3. Patients with hypertension requiring antihypertensive therapy should have a target blood pressure of less than 140/90 mmHg; (Class I recommendation; Level A of the evidence)
4. Successful BP lowering is more important for stroke risk reduction than other factors and should be individualized; (Class I recommendation; Level of evidence Class A)
5. Self-measurement and self-monitoring of blood pressure is recommended to improve blood pressure control; (Class I recommendation; Level of evidence Class A)
(E) Obesity and fat distribution.
1. For overweight (BMI: 25-29 kg/m2) and obese (BMI > 30 kmg/m2) individuals, weight loss is recommended to reduce blood pressure; (Class I recommendation; Level A of the evidence)
2. For overweight and obese individuals, weight loss is recommended to reduce the risk of stroke (Class I recommendation; Level B of the evidence)
(vi) Diabetes mellitus.
1. For patients with type 1 and type 2 diabetes, blood pressure control is recommended, consistent with the AHA/ACC/CDC Statement on the Management of Hypertension, i.e., <140/90 mmHg; (Class I recommendation; Level of evidence, Level A)
2. Statin therapy is recommended for patients with diabetes, especially those with other risks, to reduce the risk of first stroke; (Class I recommendation; Level of Evidence A)
3. The effect of aspirin on first stroke prevention is unknown in patients with diabetes mellitus with low 10-year cardiovascular risk factors (Class IIb recommendation; Level B of the evidence)
4. No benefit in stroke risk reduction in patients with diabetes mellitus treated with statins in combination with fibrates (Class III recommendation; Level of evidence Class B)
(vii) Smoking.
1. Counseling is recommended to assist smokers to quit smoking by combining replacement therapy with nicotine, bupropion, or varenicline; (Class I recommendation; Level of evidence, Level A)
2. advise patients without a history of smoking not to smoke because of the correlation between smoking and ischemic stroke and subarachnoid hemorrhage based on epidemiologic studies; (Class I recommendation; Level of evidence Class B)
3. community or statewide smoking cessation is reasonable to reduce the risk of stroke and heart attack; (IIa recommendation; Level of Evidence B)
(viii) Atrial fibrillation / AF.
1. Patients with valvular AF with a CHA2DS2-VASc score ≥2 are at higher risk for stroke and lower risk for bleeding complications; long-term anticoagulation with oral warfarin and a target INR of 2,0-3,0 is recommended; (Class I recommendation; Level of evidence Class A)
2. For patients with non-valvular atrial fibrillation with a CHA2DS2-VASc score ≥2, the risk of developing bleeding complications is low and oral anticoagulant therapy is recommended (Class I recommendation). Options include warfarin (INR:2, 0-3, 0) (Level of Evidence A), dabigatranate (Level of Evidence B), apixaban (Level of Evidence B), and rivaroxaban (Level of Evidence B). Individualized selection of antithrombotic drugs is based on patient risk factors (especially for patients at risk for intracranial hemorrhage), cost, tolerability, patient preference, and potential drug-drug interactions.
3. In primary care settings, patients >65 years of age should be proactively screened for AF, and pulse taking and subsequent electrocardiography can be useful; (Class IIa recommendation; Level of Evidence B)
4. In patients with non-valvular AF with a CHA2DS2-VASc score of 0, it is reasonable to ignore antithrombotic therapy; (Class IIa recommendation; Level of Evidence B)
5. In patients with non-valvular AF with a CHA2DS2-VASc score of 1, the risk of bleeding complications is low and anticoagulation or aspirin therapy may be considered (Class IIb recommendation, Level C of the evidence). In addition, individualized antithrombotic drug selection is based on patient risk factors (especially in patients with intracranial hemorrhage), cost, tolerability, patient preference, and potential drug-drug interactions.
6. Consider left-ear occlusion for patients with high-risk AF who are not candidates for anticoagulation; (Class IIb recommendation; Level of Evidence B)
(ix) Other cardiac problems.
1. anticoagulation is recommended for patients with mitral stenosis with embolic events; (Class I recommendation; Level of Evidence B)
2. anticoagulation is recommended for patients with mitral stenosis and left atrial thrombus; (Class I recommendation; Level B of the evidence)
3. warfarin (target INR: 2, 0-3, 0) and low-dose aspirin recommended for patients undergoing aortic valve replacement (bileaflet mechanical valve) (Class I recommendation; Level of Evidence B); warfarin (target INR: 2, 5-3, 5) and low-dose aspirin recommended for patients undergoing aortic valve replacement (mechanical valve) and risk factors (Class I recommendation; Level of Evidence B) Warfarin (target INR: 2, 5-3, 5) and low-dose aspirin are recommended for patients undergoing mitral valve replacement (mechanical valve) (Class I recommendation; Level of Evidence B). Risk factors include: AF, thromboembolic events, LV insufficiency, hypercoagulable state
4. Patients with atrial mucinous tumors for whom surgical resection is recommended (Class I recommendation; Level of Evidence C)
5. Surgical treatment is recommended for elastic fibroids >25px or appearing to move, even if asymptomatic (Class I recommendation; Level C of the evidence)
6. Aspirin is reasonable for aortic or mitral valve replacement (biosynthetic valve); (Class IIa recommendation; Level B of the evidence)
7. Warfarin therapy to achieve INR: 2,0-3,0 is reasonable for the first 3 months after aortic or mitral valve replacement (biosynthetic valve); (Class IIa recommendation; Level C of the evidence)
8. anticoagulation or antiplatelet agents are reasonable in patients with heart failure without a history of atrial fibrillation or thromboembolism; (Class IIa recommendation; Level of Evidence Level A)
9. Vitamin K antagonist therapy is reasonable in patients with acute ST-segment elevation myocardial infarction and asymptomatic left ventricular appendage thrombosis; (Class IIa recommendation; Level of Evidence C)
10. anticoagulation may be considered in asymptomatic patients with echocardiographic findings of left atrial diameter ≥55 mm and severe mitral stenosis; (Class IIb recommendation; Level of Evidence B)
11, Anticoagulation may be considered in patients with severe mitral stenosis and left atrial enlargement on echocardiography; (Class IIb recommendation; Level C of the evidence)
12. Anticoagulation may be considered in patients with acute ST-segment elevation myocardial infarction (STEMI) combined with anterior apical wall loss of motion or inversion; (Class IIb recommendation; Level of evidence Class C)
13. Anticoagulation is not recommended as primary prevention of stroke in patients with patent foramen ovale (PFO); (Class III recommendation; Level of evidence Class C)
(x) Asymptomatic carotid stenosis.
1. Patients with asymptomatic carotid stenosis should take aspirin or statins daily as prescribed by their physician. Patients should be screened for other treatable stroke risk factors, treated appropriately and have lifestyle changes made; (Class I recommendation; Level C)
2. In patients undergoing carotid endarterectomy (CEA), aspirin is recommended perioperatively and postoperatively, except where contraindicated; (Class I recommendation; Level C of the evidence)
3. In asymptomatic patients with >70% internal carotid artery stenosis, it is reasonable to consider CEA if the risk of perioperative stroke, infarction, and death is low (<3% =). However, efficacy has not been established; (Class IIa recommendation; Level of Evidence A)
4. In patients with >50% atherosclerotic stenosis, annual ultrasound Doppler examination by a technologist is reasonable to assess disease progression or regression and response to therapy; (Class IIa recommendation; Level of Evidence C)
5. For patients with highly selective asymptomatic carotid stenosis (≥60% angiographic stenosis and ≥70% ultrasound Doppler stenosis), prophylactic carotid stenting (CAS) may be considered, but its efficacy is not known; (Class IIa recommendation; Level of Evidence B)
6. In asymptomatic patients at high risk of complications from carotid revascularization, the efficacy of revascularization is not known (Class IIb recommendation; Level of Evidence B)
7. Screening for asymptomatic carotid stenosis is not recommended in low-risk groups (Class III recommendation; Level C of the evidence)
(xi) Sickle cell disease/SCD
1. For children with SCD, ultrasound Doppler screening (TCD) is recommended after 2 years of age and repeated annually until 16 years of age; (Class I recommendation; Level B of the evidence)
2. In children at increased risk, blood transfusion therapy (hemoglobin S to less than 30%) is effective in reducing stroke risk; (Class I recommendation; Level B of the evidence)
3. Although the optimal screening interval has not been determined, it is reasonable to screen younger children and those with borderline abnormal TCD flow rates more frequently to identify high-risk TCD indications requiring intervention (Class IIa recommendation; Level of Evidence B)
4. continued transfusion may be reasonable even in patients with normalized TCD flow rates; (Class IIa recommendation; Level of Evidence B)
5. It may be reasonable to consider hydroxyurea or bone marrow transplantation in children with high-risk stroke who are unable or unwilling to undergo regular red blood cell transfusion therapy; (Class IIb recommendation; Level of evidence, Level B)
6. The criteria for MRI and MRA screening of children requiring transfusion as primary stroke prevention have not been established and therefore they are not recommended to replace TCD; (Class III recommendation; Level of Evidence B).
IV. Risk factors that have not been adequately identified and that are potentially amenable to intervention (Recommendations)
(i) Migraine.
1. In women with migraine with aura, smoking cessation is strongly recommended (Class I recommendation; Level of Evidence B)
2. Alternative oral contraceptive pills (OCs) therapy (especially containing estrogen) may be considered for women with migraine with aura (Class IIb recommendation; Level of Evidence, Level B)
3. Treatment to reduce the frequency of migraine may be a reasonable way to reduce the risk of stroke; (Class IIb recommendation; Level of evidence, Level C)
4. Ovarian foramen occlusion is not recommended for stroke prevention in patients with migraine; (Class III recommendation, Level B evidence)
(ii) Metabolic syndrome.
Recommended approaches for the management of metabolic syndrome, including: lifestyle (e.g., exercise, appropriate weight reduction, proper diet), pharmacotherapy (antihypertensive agents, lipid-lowering agents, glycemic control, and antiplatelet therapy), are mentioned elsewhere in this guideline; (see specific recommendation categories and levels of evidence for each section)
(iii) Alcohol consumption.
1. For heavy drinkers, reduce or abstain from alcohol, according to the 2004 U.S. Preventive Services Task Force update; (Class I recommendation; Level of Evidence A)
2. It may be reasonable for men to consume ≤2 drinks per day and for nonpregnant women ≤1 drink per day; (Class IIb recommendation; Level of Evidence B)
(iv) Substance abuse.
Referral to an appropriate treatment program for stroke related substance abuse (including: cocaine, amphetamines, khat) is reasonable (Class IIa recommendation; Level C of the evidence)
(v) Sleep disordered breathing.
1. Because sleep breathing disorders are associated with stroke risk, screening for sleep apnea by taking a detailed history is recommended; (Class IIb recommendation; Level C of the evidence)
2. It is reasonable to reduce the risk of stroke by treating sleep apnea, although its effectiveness in preventing first-degree stroke has not been established (Class IIb recommendation; Level C of the evidence)
(vi) Hyperhomocysteinemia.
Vitamin B complex, pyridoxine (vitamin B6), cobalamin (vitamin B12), and folic acid may be considered for the prevention of ischemic stroke events in patients with hyperhomocysteinemia, but its effectiveness has not been demonstrated (Class IIb recommendation; Level of Evidence, Grade B)
(vii) Elevated lipoprotein(a) /LP(a)
1. In patients with high LP(a), it may be reasonable to use niacin to reduce LP(a) and thereby prevent ischemic stroke, but the effect of niacin has not been demonstrated (Class IIb recommendation; Level of Evidence, Class B)
2. The clinical benefit of using LP(a) to predict stroke risk has not been established; (Class IIb recommendation; Level of Evidence, Level B)
(viii) Hypercoagulable states.
1. The effectiveness of using genetic screening to detect hereditary hypercoagulable states to prevent first stroke has not been established; (Class IIb recommendation; Level C of the evidence)
2. The effectiveness of specific treatment to prevent first stroke in patients with asymptomatic hereditary or acquired embolism is not established; (Class IIb recommendation; Level C of the evidence)
3. Low-dose aspirin (81 mg/d) is not recommended for first stroke prevention in patients with persistent positive antiphospholipid antibodies; (Class III recommendation; Level of Evidence, Grade B)
(ix) Inflammation and infection.
1. Elevated risk of stroke should be considered in patients with chronic inflammatory conditions (rheumatoid arthritis or systemic lupus erythematosus) (Class I recommendation; Level of evidence Class B)
2. Annual influenza vaccination is effective in reducing the risk of stroke in patients at high risk of stroke; (Class IIa recommendation; Level B of the evidence)
3. In patients without cardiovascular disease, inflammatory markers such as serum high-sensitivity C-reactive protein (hs-CRP) or lipoprotein-associated phospholipase A2 may be considered to identify increased risk of stroke, although their effects are not well established in routine clinical work; (Class IIb recommendation; Level of evidence, Class B)
4. statins may be considered to reduce stroke risk in patients with hs-CRP >2,0 mg/dL; (Class IIb recommendation; Level of evidence Class B)
5. Antibiotics are not recommended for the treatment of chronic infections as a method of stroke prevention; (Class III recommendation; Level of evidence Class A)
V. Antiplatelet agents and aspirin.
1. The use of aspirin for prevention of cardiovascular disease (including stroke, but not specific to it) is reasonable, and in patients at high risk (10-year risk >10%), the benefits far outweigh the risks associated with treatment; (Class IIa recommendation; Level of evidence Class A)
2. Aspirin (81 mg/day or 100 mg?every other day) can be used for first stroke prevention in women, including those with diabetes, where the benefits far outweigh the risks; (Class IIa recommendation; Level of evidence Class B)
3. Aspirin may be considered for the prevention of first stroke in patients with chronic kidney disease (glomerular rate filtration <45 ml/min/1, 732 m2 = (Class IIb recommendation; Level C of the evidence). This recommendation does not apply to severe kidney disease (stages 4 and 5, glomerular rate filtration <30 ml/min/1, 732m2 =).
4. cilostazol may be reasonable for first stroke prevention in patients with peripheral arterial disease; (Class IIb recommendation; Level of evidence Class B)
5. Aspirin is not effective for first stroke prevention in low-risk individuals (Class III recommendation; Level of Evidence, Level A)
6. Aspirin is not effective for the prevention of first stroke in patients with diabetes mellitus but without other risk factors (Class III recommendation; Level A of the evidence)
7. Aspirin is not effective for the prevention of first stroke in patients with diabetes mellitus with asymptomatic (ankle-arm pressure index ≤0,99) peripheral artery disease (Class III recommendation; Level of evidence Class B)
8. the use of aspirin in other special circumstances (e.g. AF, carotid stenosis, etc.) has been discussed in the relevant section of this article
9. Due to the lack of clinical trials, antiplatelet agents other than aspirin and cilostazol are not recommended for first stroke prevention; (Class III recommendation; Level C of the evidence)
VI. Primary prevention of stroke in the emergency room
1. Smoking cessation programs and interventions are recommended in the ED; (Class I recommendation; Level of evidence Class B)
2. Identification of AF and anticoagulation assessment in the ED is recommended; (Class I recommendation; Level of evidence Class B)
3. It is reasonable to screen patients in the ED for hypertension; (Class IIa recommendation; Level C of the evidence)
4. When a patient is found to have a drug or alcohol abuse problem, it is reasonable to refer him or her to an appropriate treatment program; (Class IIa recommendation; Level C of the evidence)
5. The effectiveness of screening, brief interventions and treatment for diabetes, lifestyle (obesity, alcohol/substance abuse, sedentary lifestyle) in the emergency room setting is not clear; (Class IIb recommendation; Level C evidence)
VII. Preventive Health Services
Systematic identification and treatment of patients at risk for stroke through appropriate programs is reasonable (Class IIa recommendation; Level A of the evidence).