Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of the management of high-risk population



## Correspondence to

# Introduction
In the past two decades, stroke has been a big healthcare burden in China. From the results of 2013 national survey, the age-adjusted stroke incidence and mortality rates were 246.8/100 000 and 114.8/100 000 person-years, respectively. Stroke prevalence was 1114.8/100 000. Based on this calculation, there are >11 million stroke survivors, >2.4 million new strokes and >1.1 million people dying of stroke every year in China. The disability-adjusted loss of life-years was 2010.0/100 000 person-years. In addition, there are approximately 270 million patients with hypertension, 110 million with diabetes mellitus and 160 million with dyslipidaemia and the number of people with these risk factors of stroke continues to rise in China.The best treatment of stroke is prevention. Many studies showed that primary prevention is the key to reduce stroke incidence and mortality. The aim of this guideline is to recommend the appropriate prevention strategies for population at high risk for stroke. This executive summary offers a simplified version of the comprehensive recommendations that have been published, but with an update since the publication of the original version. The recommendations and levels of evidence are in line with the American Heart Association (AHA) guidelines for the primary prevention of stroke. 

## Controlling the risk factors of stroke genetic factors
Recommendations  Inquiring a family history can help identify individuals at increased risk of stroke (class IIa; level of evidence A).  For patients with rare genetic causes of stroke (such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, COL4A1-related intracerebral haemorrhage, autosomal-dominant polycystic kidney disease, Ehlers-Danlos type IV), referral for genetic counselling may be considered (Class IIb; level of evidence C). In general population routine genetic screening for the prevention of a first stroke is not recommended (class III; level of evidence C).
 For patients with 2 first-degree relatives with SAH or intracranial aneurysms, non-invasive screening such as CT Angiography (CTA) or MR Angiography (MRA) of brain for detecting any unruptured intracranial aneurysm (UIA) may be reasonable (class IIb; level of evidence C).  For patients with autosomal-dominant polycystic kidney disease, 1 relatives with autosomal-dominant polycystic kidney disease and subarachnoid hemorrhage (SAH) or 1 relatives with autosomal-dominant polycystic kidney disease and intracranial aneurysms, non-invasive screening such as CTA or MRA of brain for detecting any UIAs may be considered (class IIb; level of evidence C).  For patients with (cervical) fibromuscular dysplasia, non-invasive screening such as CTA or MRA brain for detecting any UIAs may be considered (class IIb; level of evidence C). DSA can be conducted if needed. It is reasonable to consider a first follow-up at 6-12 months after initial discovery of UIA, and follow-up every 1-2 years (class IIa; level of evidence C).  Treatment includes surgical clipping and endovascular treatment. Treatment selection is related to multiple factors including aneurysm location, size and morphology; documented growth of aneurysms during the follow-up; the age of the patient; history of aSAH; family history of cerebral aneurysm; the presence of multiple aneurysms or the presence of concurrent pathology such as an arteriovenous malformation or other cerebrovascular or inherited pathology (class I; level of evidence C). The management of patients with UIAs (figure 5).

## Modifiable risk factors

## Cigarette smoking
Recommendations  Smoking cessation ought to involve both smokers and the whole society, by adopting comprehensive tobacco control measures including psychological counselling, nicotine replacement, smoking cessation medications, and intervention in the community (class I; level of evidence A).  Non-smokers should avoid passive smoking (class I; level of evidence B).  Publicity and education should continue to be strengthened to raise public awareness of the harm of active and passive smoking. Local government should legislate against smoking in public places as soon as possible, such as smoking bans in offices, meeting rooms, airplanes or trains, to reduce the harm of smoking (class IIa; level of evidence B).

## Alcohol consumption
Recommendations  Drinkers should reduce or eliminate alcohol consumption (class I; level of evidence A).  Drinking only in moderation should be recommended among individuals who choose to consume alcohol. Moderate alcohol consumption of 25 g/day for men and half for women is reasonable (class IIb; level of evidence B).

## Obesity and body fat distribution

## Open access

## Diet and nutrition
Recommendations  Daily diet should be diverse to make the intake of energy and nutrition more reasonable; a balanced diet including whole grains, legumes, tubers, fruits, vegetables, dairy product and a low intake of total fat and saturated fat is recommended (class I; level of evidence A).  Reducing the intake of salt and increasing the intake of potassium are recommended to reduce the risk of stroke by lowing BP. A salt intake of 6 g/day is recommended (class I; level of evidence A).  Encouraging more intake of fruits, vegetables and certain dairy product, and reducing the intake of saturated fat and trans fatty acids (class I; level of evidence A). The total fat intake per day should be less than 30% of total calories and trans fatty acids of less than 2 g; fresh vegetables intake of 400-500 g; fruits intake of 200-400 g; moderate consumption of fish, poultry, eggs and lean meat, with an average total intake of 120-200 g; various dairy product, with an intake equivalent to 300 g of liquid milk; vegetable oil intake of <25 g; added sugar (or free sugar, ie, the monosaccharide added in food, such as rock candy, refined cane sugar, etc) intake of <50 g/day, preferably <25 g/day.

## Physical inactivity
Recommendations  Appropriate physical activities are recommended to reduce the risk of stroke (class I; level of evidence B).
In elderly and high-risk people, individualised exercise programme should be planned, after conducting a safer maximal exercise tolerating test.  Healthy adults should perform at least moderate-tovigorous-intensity aerobic physical activity (such as brisk walking, jogging, cycling or other aerobics) for at least 40 min per day for 3-4 days per week (class I; level of evidence B).  Standing up and moving limbs around for a few minutes after an hour of sitting still is recommended for people who are sedentary in their daily work, including those who have already had enough regular exercise weekly is recommended (class I; level of evidence C).

## Evidence insufficient or potential modifiable risk factors
Metabolic syndrome Recommendations  Metabolic syndrome is a clinical condition in which multiple metabolic abnormalities occur in the human body, including central obesity (abdominal obesity), dyslipidaemia, hypertension and elevated fasting blood glucose. Metabolic syndrome is increasingly common. Interventions of every single risk factor of the metabolic syndrome are recommended, including lifestyle measures and pharmacotherapy (ie, medications for BP lowering, lipid-lowering, glycaemic control, etc). Detailed interventions refer to relevant sections on 'hypertension', 'abnormal glucose metabolism', 'dyslipidaemia' of this guideline.

## Sleep-disordered breathing
Recommendations  Screening for patients with sleep apnoea requires a detailed history. The screening methods include structured questionnaires such as the Epworth Sleepiness Scale, Berlin Questionnaire, physical examination. And polysomnography may be considered depending on the patients' condition (class IIb; level of evidence C).  The effectiveness of treatment for sleep apnoea in stroke prevention is still not well established (class IIb; level of evidence C).

## Migraine
Recommendations  For women and geriatric patients with migraine with aura, smoking cessation is recommended (class I; level of evidence B).  For women with active migraine with aura, withdrawal of oral contraceptives (OCs), especially those containing oestrogen, should be considered (class IIa; level of evidence B).  Treatments to reduce migraine frequency (especially for migraines with specific aura symptoms) might be able to reduce the risk of stroke (class IIa; level of evidence B).  For patients with migraine, the clinical benefit of closing PFO for the prevention of stroke is unproven (class III; level of evidence B).

## Hyperhomocysteinaemia
Recommendations  Hyperhomocysteinaemia is a risk factor of stroke (level of evidence A). For patients with hyperhomocysteinaemia, the use of folic acid or folic acid in combination with cobalamin (B12) and pyridoxine (B6) might be effective in the prevention of stroke (class IIa; level of evidence B).

## Elevated lp(a)

## Hypercoagulability
Recommendations  For patients with inherited hypercoagulable states, the effectiveness of genetic screening for the prevention of stroke is not well established (class IIb; level of evidence C).  The effectiveness of treatments for the primary prevention of stroke in asymptomatic patients with a Open access glomerular filtration rate <30 mL/min/1.73 m 2 ), aspirin is not recommended anymore.  Aspirin is not recommended for preventing a first ever stroke in low-risk individuals whose 10 year risk is less than 10% (class III; level of evidence A).  Aspirin is not recommended for preventing a firstever stroke in people over 70 years old (class III; level of evidence B).

## Assessing the risk of first stroke recommendations
The use of a risk assessment tool is reasonable and can help identify individuals who could benefit from therapeutic interventions. For high-risk individuals, treatment decisions should be individualised according to the overall risk profile of the patient (class IIa; level of evidence B .
Contributors WW, YW, YJ, and ZL designed the protocol and framework. WW, BJ, XR, DS and HS drafted the sections of unmodifiable risk factors, cigarette smoking, alcohol consumption, obesity and body fat distribution, diet and nutrition, and physical inactivity. XX drafted the section of hypertension. QJ drafted the section of diabetes and prediabetes. HZ and YY drafted the sections of dyslipidaemia and elevated Lp(a). SL and XY drafted the sections of atrial fibrillation and other heart diseases. HQ, LZ and YumX drafted the section of asymptomatic extracranial or intracranial stenosis. YC and YJ drafted the section of unruptured intracranial aneurysms. PW and TW drafted the sections of metabolic syndrome and infection and inflammation. HQ and MZ drafted the sections of sleep-disordered breathing and antiplatelet agents and aspirin.
LG drafted the section of migraine. WL drafted the section of hyperhomocysteinaemia. HZ and SH drafted the sections of hypercoagulability, drug abuse, oral contraceptives and postmenopausal hormone therapy. YL, YG and YuyX drafted the section of assessing the risk of first stroke. WW, YW, HZ, HQ, BJ and SH discussed and updated the final version. SH and LG did the translation for the supplement material.
Funding This research received specific funding from Chinese Stroke Association Guidelines Writing Committee.
Competing interests None declared. Patient consent for publication Not required. Provenance and peer review Commissioned; externally peer reviewed.
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