Cerebrovascular disease has become one of the major health hazards of the population, characterized by high prevalence, high disability, high mortality and high recurrence rates. Epidemiological survey data show that there are (1,50~2) × 106 new stroke patients and 7 × 106 existing stroke patients in China each year, of which about 85% are ischemic strokes. Stroke can be divided into hemorrhagic and ischemic, and from the above ratio, we should pay more attention to hemorrhagic stroke. Stroke has a high recurrence rate, so secondary prevention of ischemic stroke should be given more attention. Risk factors for ischemic stroke are divided into preventable and non-preventable risk factors, the former including hypertension, diabetes, dyslipidemia, hyperhomocysteinemia, nutritional status, obesity, patent foramen ovale, smoking, alcohol abuse, and physical activity; the latter including gender, age, race, and genetic factors. The latter includes gender, age, race, and genetics. This article discusses secondary prevention strategies for ischemic stroke with respect to preventable risk factors.
Intervention strategies for risk factors
1. Prevention and treatment of hypertension
Studies have shown that hypertension is an important independent risk factor for stroke, and the relationship between the two is continuous and consistent. The higher the blood pressure, the greater the risk of stroke. Early treatment of hypertension can significantly reduce the incidence of stroke. According to the Chinese Guidelines for the Prevention and Treatment of Hypertension 2010, there is a log-linear relationship between blood pressure and stroke incidence, with a 49% increase in the relative risk of stroke for every 10 mm Hg increase in baseline systolic blood pressure (1 mm Hg = 0.133 kPa) and a 46% increase in the relative risk of stroke for every 5 mm Hg increase in diastolic blood pressure; the effect of hypertension on stroke incidence in Asian populations is approximately 1.50 times greater than that in Western populations. The relative risk of stroke increases by 46% for every 5 mm Hg increase in diastolic blood pressure.
The Chinese Guidelines for the Management of Acute Ischemic Stroke 2010 recommend a target blood pressure of ≤ 140/90 mm Hg for patients with ischemic stroke and transient ischemic attack (TIA), and ≤ 130/80 mm Hg for patients with combined diabetes and chronic kidney disease. The 2014 guidelines for secondary stroke prevention state that a reasonable goal for blood pressure lowering in patients with recent lacunar infarction is a systolic blood pressure <130 mm Hg. Antihypertensive therapy can be monotherapy or combination of drugs and the treatment plan is based on the principle of individualization.
2. Prevention and treatment of glucose abnormalities
Diseases related to abnormal glucose metabolism include type 1 and type 2 diabetes and prediabetes. The latter is divided into abnormal fasting glucose (IFG) and abnormal glucose tolerance (IGT), and about 95% of pre-diabetic patients progress to diabetes. As seen in the AHA/ASA 2014 guidelines for secondary stroke prevention, the prevention, diagnosis and treatment of prediabetes are receiving increasing attention. Diabetes is an independent risk factor for stroke, and patients with diabetes are 2 ~ 3 times more likely to have an ischemic stroke than normal. The AHA/ASA 2014 guidelines for secondary stroke prevention recommend that patients with ischemic stroke or transient ischemic attack should be screened for diabetes with fasting glucose, glycosylated hemoglobin (HbA1c) or oral glucose tolerance test (OGTT), of which Glycosylated hemoglobin may be more sensitive than other indicators.
The American Diabetes Association (ADA) recommends that blood glucose levels be controlled through proper diet, exercise, oral hypoglycemic agents and subcutaneous insulin injections. Patients with diabetes should control glycosylated hemoglobin level <6,50%, fasting blood glucose 4,40~6,10 mmol/L, non-fasting blood glucose 4,40 ~ 8 mmol/L; for patients with diabetes combined with hypertension, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) can be chosen.
3. Control of dyslipidemia
The results of the Study on the Prevention of Recurrent Stroke by Active Cholesterol Reduction (SPARCL) showed that elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL?C) are strongly associated with ischemic stroke. Statins can reduce the incidence of ischemic stroke, and there is a consensus that these drugs (e.g., atorvastatin, rasulvastatin, etc.) are preferred to control hyperlipidemia.
Patients with total serum cholesterol >6,24 mmol/L (240 mg/dl) are susceptible to stroke; in patients who have had a stroke, LDL cholesterol should be reduced to <2,60 mmol/L (100 mg/dl) or by 30% to 40%; in patients with multiple risk factors, such as coronary artery disease, diabetes mellitus, atherosclerotic plaque formation, or ischemic stroke, or transient ischemic attack, patients should be treated with a statin. For patients with ischemic stroke or transient ischemic attack with multiple risk factors such as coronary artery disease, diabetes mellitus, or atherosclerotic plaque formation (considered very high risk group II), LDL cholesterol should be reduced to < 2,10 mmol/L (80 mg/dl) or by >40%; for patients with ischemic stroke or transient ischemic attack with intracranial and extracranial large atherosclerotic vulnerable plaques or evidence of arterial embolism (considered very high risk group I), regardless of whether they have lipid abnormalities, early initiation of intensive therapy is recommended. Early initiation of intensive statin therapy is recommended, regardless of dyslipidemia, and LDL cholesterol should be reduced to <2,10 80="">40%.
The AHA/ASA 2014 guidelines for secondary stroke prevention recommend that intensive statins be used to reduce the risk of stroke or cardiovascular events in patients with ischemic stroke or transient ischemic attack with or without other atherosclerotic cardiovascular disease with LDL cholesterol levels ≥2, 60 mmol/L (100 mg/dl); intensive statins may also be used in patients with LDL cholesterol levels <2, 60 mmol/L (100 mg/dl) with other atherosclerotic cardiovascular disease. ischemic stroke or transient ischemic attack in patients with LDL cholesterol levels <2,60 mmol/L (100 mg/dl) without clinical evidence of other atherosclerotic cardiovascular disease, in agreement with the 2013 American College of Cardiology (ACC)/AHA guidelines for the treatment of cholesterol to reduce the risk of atherosclerotic cerebrovascular disease in adults. The ongoing Treatment for Stroke Stabilization (TST) trial may provide more favorable evidence for lipid level control in secondary stroke prevention.
4. Antithrombotic therapy for non-cardiogenic embolism
Traditionally, antithrombotic therapy includes antiplatelet therapy and anticoagulation, both of which are important for secondary prevention of stroke.
(1) Antiplatelet therapy: Antiplatelet agents are essential for secondary stroke prevention and are the most well-researched drugs, including aspirin, clopidogrel, disopyramide, cilostazol, etc. Numerous studies have shown that low-dose aspirin maximally inhibits thromboxane A2 (TXA2) expression, significantly reduces ischemic stroke and transient ischemic attack, and is the drug of choice for antiplatelet therapy. There is no significant difference in the effect of small (<160 mg/d), medium to small (160 ~ 325 mg/d) and high (500-1500 mg/d) doses of aspirin on stroke prevention. Typically, aspirin doses of 50 ~ 325 mg/d, or aspirin 25 mg/d combined with dipyridamole 200 mg (2 doses/d), or clopidogrel 75 mg/d alone are used. high-dose aspirin carries some risk of bleeding, so clopidogrel may be an option for patients with contraindications or adverse effects to aspirin. aha/asa 2014 The secondary stroke prevention guidelines recommend continued clopidogrel combined with aspirin antiplatelet therapy for 90 days within 24 hours of onset in patients with ischemic stroke or transient ischemic attack. The combination of clopidogrel with aspirin is also recommended for patients with acute coronary syndromes (e.g., unstable angina, Q-wave-free myocardial infarction) or recent endovascular stenting.
(2) Anticoagulation: The results of the European and Australian Reversible Ischemic Stroke Prevention Trial (ESPRIT) showed that warfarin did not show an advantage over aspirin in the secondary prevention of stroke in patients with non-cardiogenic embolism and increased the risk of bleeding, so it is not recommended as the first choice for anticoagulation.
5. Antithrombotic treatment of cardiogenic embolism
The former etiology generally includes atrial fibrillation, acute myocardial infarction and left ventricular appendage thrombosis, cardiac valve disease, cardiac prosthetic valve replacement, cardiomyopathy, and cardiac failure.
(1) Atrial fibrillation: It is the most common cause of cardiogenic embolism, and about 70% is non-valvular atrial fibrillation. The AHA/ASA 2014 guidelines for secondary stroke prevention recommend that in patients with acute ischemic stroke or transient ischemic attack with no apparent cause, approximately 30 heart rate monitoring visits within 6 months of onset are required and can This can identify approximately 11% of additional patients with AF, providing a basis for anticoagulation. In addition to the traditional drug warfarin, the AHA/ASA 2014 guidelines for secondary stroke prevention recommend the use of new oral anticoagulants (NOACs) such as apixaban, dabigatran, and rivaroxaban for secondary stroke prevention in patients with atrial fibrillation. Patients with stroke with AF should be anticoagulated within 14 days of the onset of neurological symptoms, or after 14 days if there is a greater risk of bleeding, if appropriate. Aspirin alone is recommended when there is a contraindication to anticoagulation.
(2) Acute myocardial infarction and left ventricular appendage thrombus: the proportion of cardiogenic embolism within 2-4 weeks after acute myocardial infarction is about 2, 50%, and the emboli mostly originate from left ventricular appendage thrombus. Increased age, thrombus size, and tipped thrombus are all risk factors for stroke. In patients with acute myocardial infarction and left ventricular appendage thrombosis combined with stroke, continuous warfarin anticoagulation for more than 3 months and maintenance of an international normalized ratio (INR) of 2 to 3 are recommended, together with antiplatelet therapy. When patients cannot tolerate vitamin K blockers, consider apixaban, low molecular heparin, dabigatran or rivaroxaban replacement therapy.
(3) Heart valve disease: There are various types of heart valve disease. For patients with rheumatic mitral valve lesions, prosthetic or biological valves, and mitral valve closure insufficiency, warfarin anticoagulation therapy is recommended with a target dose of maintaining an international standardized ratio of 2 to 3; for patients with mitral valve prolapse and aortic valve lesions, antiplatelet agents are recommended, usually clopidogrel in combination with aspirin; for rheumatic mitral valve lesions applying In patients with ischemic stroke despite warfarin application, additional antiplatelet agents are recommended; in patients with mitral valve calcification, antiplatelet agents or anticoagulants are recommended; in patients undergoing cardiac prosthetic valve replacement, warfarin anticoagulation is recommended, and the international standardized ratio of 2 to 3 for prosthetic aortic valves and 2.50 to 3.50 for prosthetic mitral valves can be maintained, with additional aspirin if there is no higher risk of bleeding. Patients with ischemic stroke prior to bioprosthetic heart valve replacement should be treated with warfarin and long-term aspirin 75-100 mg/d for 3-6 months after surgery if no anticoagulation is indicated.
(4) Cardiomyopathy and heart failure: dilated cardiomyopathy can be caused by various reasons, such as viral infection, poisoning, malnutrition, etc. However, primary cardiomyopathy is common in young people and has a poor prognosis, mainly manifested by progressive heart failure, arrhythmias and thrombosis. In patients with ischemic stroke and transient ischemic attack with dilated cardiomyopathy, anticoagulation therapy can be considered and the international standardized ratio can be maintained at 2~3. Apixaban, dabigatran or rivaroxaban can be given to prevent stroke recurrence, but the effect is unclear. For patients with heart failure, the AHA/ASA 2014 guidelines for secondary stroke prevention recommend antiplatelet therapy.
6. Surgical treatment of carotid atherosclerotic plaque and carotid stenosis
Carotid atherosclerotic plaque and carotid stenosis are also important risk factors for ischemic stroke, affecting cerebral blood flow on the one hand and causing embolic stroke due to the formation of emboli from dislodged plaque on the other. Carotid endarterectomy (CEA) and carotid stenting (CAS) are the two most commonly used procedures for ischemic stroke patients with carotid artery stenosis or occlusion.
(1) Carotid endarterectomy: The North American Symptomatic Carotid Endarterectomy Trial (NASCET), the European Carotid Surgery Trial (ECST) and the US Department of Veterans Affairs Joint Research Program (VACSP) have all shown that carotid endarterectomy is important for the treatment of carotid stenosis.
(2) Carotid stenting: It is a popular treatment for carotid stenosis in recent years, and some randomized controlled clinical trials [such as the Carotid and Vertebral Artery Angioplasty Study (CAVATAS), the Endarterectomy and Stenting in Patients with Symptomatic Severe Carotid Stenosis Study (EVA?3S), the Protective Stent Angioplasty with Carotid Endarterectomy (SPACE), the International The International Carotid Stenting Study (ICSS)] compared the outcomes of carotid endarterectomy with carotid stenting and showed no significant difference in prognosis between the two treatments in patients younger than 70 years. Compared with carotid endarterectomy, carotid stenting reduces cerebral nerve injury and complications related to carotid hematoma, but has a higher restenosis and mortality rate. Carotid stenting may be considered when the procedure is risky, when there is a contraindication to the procedure, or when the stenosis cannot be reached by the procedure. The combination of clopidogrel and aspirin should be administered preoperatively and continued until at least 1 month after the procedure, after which clopidogrel alone should be administered for at least 12 months. Carotid color Doppler ultrasound (CDUS) is generally not recommended for long-term follow-up of extracranial segment of the carotid circulation.
7. Hyperhomocysteinemia
Homocysteine is a sulfhydryl-containing amino acid, mainly derived from methionine in food, and is an important intermediate in the metabolism of methionine and cysteine. Previous studies have shown an increased incidence of ischemic stroke in patients with hyperhomocysteinemia. However, the results of recent randomized controlled clinical trials [e.g., the Heart Event Prevention Evaluation Study?2 (HOPE?2), Vitamins for Stroke Prevention (VITATOPS)] have shown that lowering plasma homocysteine levels does not prevent stroke recurrence well, so the AHA/ASA 2014 guidelines for secondary stroke prevention state that after an acute ischemic stroke or transient ischemic attack, it is not Monitoring of plasma homocysteine levels is recommended, and appropriate folic acid and vitamin supplementation may be indicated if its expression is elevated.
8. Good lifestyle habits
Smoking, alcohol abuse, and lack of reasonable exercise are associated with the prevention and treatment of ischemic stroke. The AHA/ASA 2014 guidelines for secondary stroke prevention recommend that patients with ischemic stroke or transient ischemic attack have at least 40 minutes of moderate intensity aerobic exercise at least once to three times a week to reduce stroke recurrence. For obese patients, body mass index (BMI) needs to be monitored to adjust the reasonable amount of exercise.
9. Nutrition
The AHA/ASA 2014 guidelines for secondary stroke prevention classify nutrition-related problems into three categories, namely malnutrition, micronutrient deficiency and excess, and reasonable eating habits. Patients with previous ischemic stroke or transient ischemic attack are recommended to have a sodium intake <2, 40 g/d or even down to 1, 50 g/d, and the Mediterranean diet is recommended as a reasonable dietary habit.
10. Sleep apnea syndrome
Sleep apnea syndrome (SAHS) has some correlation with the prognosis of stroke. Studies have shown that more than 50% of patients with stroke or transient ischemic attack have sleep apnea syndrome. However, 70% to 80% of patients cannot be clearly diagnosed and treated accordingly. Sleep apnea syndrome is strongly associated with poor prognosis in cerebrovascular disease, including death and disability rates. Clinical studies have shown that patients with ischemic stroke or transient ischemic attack combined with sleep apnea syndrome can be treated with continuous positive airway pressure ventilation (CPAP) to improve the prognosis.
11. Ovarian foramen ovale failure
Ovular foramen anion closure can be found in 15% to 20% of adults. Clinical studies have shown that patent foramen ovale is closely associated with cryptogenic ischemic stroke, which allows deep vein emboli to enter the intracranial arteries. Patients with ischemic stroke with patent foramen ovale are usually treated with antiplatelet therapy, and in case of recurrent deep vein thrombosis, foramen ovale closure may be considered.
Outlook
In conclusion, as the standard of living improves and the proportion of elderly patients increases, we should pay more attention to secondary prevention of ischemic stroke. Advances in clinical trials and the development of new drugs have allowed us to identify more and more clinical evidence and relevant influencing factors, which provide a solid foundation for secondary prevention of ischemic stroke, and reasonable drug therapy and good lifestyle habits can significantly reduce the recurrence, disability and death rates of ischemic stroke. However, the work of stroke prevention and treatment is still arduous and requires the joint efforts of workers from all walks of life.