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Secondary Prevention Of Stroke

2. Lifestyle Behaviours and Risk Factor Management

7th Edition – 2020 UPDATED


Recommendations

Note: These recommendations are applicable to stroke of ischemic, hemorrhagic and transient ischemic attack in origin unless otherwise stated.

2.1 Risk Factor Assessment
  1. Persons at risk of stroke and patients who have had a stroke or transient ischemic attack should be assessed for vascular disease risk factors, lifestyle management issues (diet, sodium intake, exercise, weight, alcohol intake, smoking), as well as use of oral contraceptives or hormone replacement therapy [Evidence Level B]. 
  2. Persons at risk of stroke or transient ischemic attack and their family members should receive individualized information and counselling about possible strategies to modify their lifestyle and vascular risk factors [Evidence Level B]. 
  3. Referrals to appropriate specialists should be made to support and manage specific vascular risk factors and lifestyle behaviours and choices where required [Evidence Level B].
2.2 Healthy Balanced Diet
  1. Counsel and educate individuals with transient ischemic attack or stroke to follow a healthy eating pattern and balanced diet [Evidence Level B] or refer to a Registered Dietitian where available [Evidence Level C]. Refer to  Canada’s Food Guide for additional information.
  2. Counsel and educate individuals with transient ischemic attack or stroke to follow a Mediterranean-type or DASH (Dietary Approach to Stop Hypertension) diet, which is high in vegetables, fruit, whole grains, fish, nuts and olive oil and low in red meat [Evidence Level B].
  3. Counselling may include:
    1. consuming a variety of natural, whole, and minimally processed foods at each meal [Evidence Level B]. 
    2. consuming fewer highly processed foods, which include refined foods, confectionaries, sugary drinks, processed meats and meat alternatives, and pre-prepared foods [Evidence Level B]. 
    3. consuming a diet high in vegetables and fruit; encourage patients to choose fresh or frozen unsweetened fruit, or fruit canned in water without added sugars and low in sodium; fresh or frozen vegetables without added sauces, or canned vegetables with no added salt [Evidence Level B].
    4. consuming lower fat and lower sugar dairy products and unsweetened fortified soy beverages [Evidence Level B].  
    5. shift to consuming more protein from plant-based sources (legumes, nuts and seeds) and other protein options which are lower in saturated fats such as fish, poultry, and lean meats [Evidence Level B]. 
    6. consuming high fibre choices such as whole grains, beans, and legumes instead of processed or refined grains such as white bread and pasta [Evidence Level B].
    7. consuming water as the drink of choice for hydration. Sugary drinks (such as energy drinks, fruit drinks, juice, soft drinks, and flavored coffees) add calories and have little to no nutritional value and should be discouraged [Evidence Level A].
    8. consuming foods low in sodium [Evidence Level B]. Refer to Section 2.3 for details.

Section 2.2 Clinical Consideration

  1. Counsel and educate individuals regarding healthy eating patterns that focus on whole, natural, minimally processed foods, instead of specific nutrients such as dietary cholesterol.
2.3 Sodium Intake
  1. To prevent hypertension and to reduce blood pressure in patients with hypertension, counsel and educate individuals with transient ischemic attack or stroke to reduce sodium intake to a goal of no more than 2000 mg (5 g table salt or 87 mmol sodium, equal to less than one teaspoon) per day [Evidence Level A]. Refer to the Hypertension Canada 2020 Guidelines on Health Behaviour Management for additional information.

Section 2.3 Clinical Consideration

  1. Achieving a sodium intake of < 2000 mg may be very difficult for the general population and average daily intake among people in Canada is 2760 mg.  Encourage a gradual decrease in foods that are high in sodium which will allow taste buds and behaviour to adapt appropriately. (https://www.canada.ca/en/health-canada/services/food-nutrition/healthy-eating/sodium.html  )
2.4 Physical Activity
Refer to CSBPR Rehabilitation and Recovery Module 2020 Section 6 and the AEROBICS 2020 Update for additional information. 
  1. Counsel and educate individuals with transient ischemic attack or stroke to reduce sedentary behaviors and sedentary time, and to work towards increased activity goals as tolerated [Evidence Level B].
  2. Most individuals post stroke who are medically stable should start a regular exercise program [Evidence Level B].
  3. Counsel and educate individuals with transient ischemic attack or stroke to participate in aerobic exercise 4 to 7 days per week, to accumulate at least 150 minutes per week in episodes of 10 minutes or more, in addition to routine activities of daily living [Evidence Level B].
  4. Initiation of aerobic training should be considered after a stroke or transient ischemic attack once the patient is medically stable. To ensure continuity of appropriate interventions, patients should be reassessed at transition points along the continuum of care based on changing neuromotor and cardiopulmonary capacities to participate in aerobic training [Evidence Level B].

Section 2.4 Clinical considerations 

  1. Aerobic exercise intensity should be individualized. Factors to consider include functional limitation, co-existing medical problems such as cardiac disease, need for an exercise stress test with electrocardiogram, and planned exercise intensity (i.e., light, moderate, or vigorous).
  2. Screening and supervision of adults with comorbid disease such as cardiac disease which places them at higher risk of medical complications should be considered.
  3. Supervision by a healthcare professional (such as a physiotherapist) at exercise initiation should be considered in individuals with stroke at risk of falls or injury.
2.5 Weight Management
  1. Counsel and educate individuals with transient ischemic attack or stroke to achieve and maintain a waist circumference of <88 centimeters for women and <102 centimeters for men*, or a body mass index (BMI) of 18.5 to 24.9 kg/m2 [Evidence Level B].   (*Note: these numbers are reflective of current research based mostly on Caucasian patients. Refer to Reference list for waist circumference values for other ethnic groups)
  2. Counsel and educate individuals with transient ischemic attack or stroke who are overweight to set healthy weight loss goals and develop individualized plans to achieve goals [Evidence Level B].    
  3. A multi-pronged approach should be used to support sustainable weight loss or weight gain that includes counselling and education, increased physical activity, and behavioural interventions [Evidence Level B].

Section 2.5 Clinical Consideration 

  1. When discussing weight, consider completion of a comprehensive history that explores root causes of weight gain and avoids stigma and judgment. Refer to 2020 Canadian Obesity Network guidelines for additional information.

 

 

2.6 Alcohol Consumption
  1. Counsel and educate individuals with transient ischemic attack or stroke to avoid heavy alcohol use as excessive alcohol intake increases the risk of hypertension, ischemic stroke and intracerebral hemorrhage.  [Evidence Level B].  
  2. Counsel and educate individuals with transient ischemic attack or stroke to follow Canada’s Low-Risk Alcohol Drinking Guidelines (2018): for women, no more than 10 drinks per week, with no more than 2 drinks per day most days and no more than 3 drinks on any single occasion; for men, no more than 15 drinks per week, with no more than 3 drinks per day most days and no more than 4 drinks on any single occasion [Evidence Level B].

Note: one standard drink is considered to be approximately 44 mL (1.5 oz) of 80 proof (40%) spirits, 355 mL (12 oz) of 5% beer or 148 mL (5 oz) of 12% wine.

2.7 Recreational Drug Use
  1. Individuals with stroke and known recreational drug use that may increase the risk of stroke (such as cocaine, amphetamines) should be counseled to discontinue use [Evidence Level C]; and should be provided with appropriate support and referrals to services and resources for drug addiction and rehabilitation. 
  2. For cannabis, that may be prescribed for medical indications, counsel patients regarding any potential increased risk of stroke to support informed decision-making regarding the use of these agents [Evidence Level B].

Section 2.7 Clinical Consideration 

At present, there has been some association of smoking cannabis products with possible increased stroke and cardiovascular events. However, there is a lack of high-quality evidence to provide clear guidance.  Individual patient factors should be considered. Refer to 2020 Canada’s Lower-Risk Cannabis Use Guidelines (Fischer et al 2017; DOI: 10.2105/AJPH.2017.303818.)

 

 
2.8 Smoking Cessation

Note, the term ‘Smoking’ in these recommendations refers to tobacco and other inhaled substances.

  1. In all healthcare settings along the stroke continuum (inpatient, ambulatory, and community), patient smoking status should be identified, assessed, and documented [Evidence Level A]. 
  2. Provide unambiguous, non-judgmental, and patient-specific advice regarding the importance of cessation to all smokers [Evidence Level B] and others who reside with the patient.  
  3. Offer assistance with the initiation of a smoking cessation attempt – either directly or through referral to appropriate resources [Evidence Level A]. 
  4. A stepwise approach that starts with reduction in smoking and progresses to full cessation is a valid approach [Evidence Level B].
  5. A combination of pharmacotherapy and behavioural therapy should be considered in all smoking cessation programs and interventions [Evidence Level A]. 
  6. The three classes of pharmacological agents that should be considered as first-line therapy for smoking cessation are nicotine replacement therapy, varenicline and bupropion [Evidence Level A]. 
    1. The choice of appropriate pharmacotherapy should take into account the patient’s medical stability, clinical needs, other medical factors, patient preferences and patient’s ability to afford the therapy in those cases where it is not covered under a provincial drug formulary [Evidence Level C]. Refer to Appendix Three: Pharmacotherapy in Smoking Cessation Treatment.
    2. The initiation of pharmacotherapy for smoking cessation should begin as soon as possible and supported while in hospital for index stroke-related event [Evidence Level C]. Earlier initiation of smoking cessation discussions may be beneficial [Evidence Level C].
  7. For stroke patients in hospital who are current smokers, protocols should be in place to manage nicotine withdrawal during hospitalization [Evidence Level B].  Refer to Implementation Resources below for the Ottawa Model as an example of protocol tool
  8. Interdisciplinary team members should counsel patients, family members, and caregivers about the harmful effects of exposure to environmental (second – hand) smoke [Evidence Level B].  
  9. A referral to virtual smoking cessation services, smoking cessation programs, supportive resources and clinics should be considered depending on regional availability to optimize the success of smoking cessation [Evidence Level B]
  10. People who are not ready to quit should be offered a motivational intervention to help enhance their readiness to quit [Evidence Level B]. Refer to Implementation Resources below for Motivational interviewing tools

Section 2.8 Clinical Considerations

Use of E-Cigarettes

  1. While some individuals may find vape products helpful in smoking cessation, the evidence base around their population-based effectiveness is not clear. 
  2. There is some evidence that shows people who use vaping as a mechanism to quit cigarettes may continue to vape even after cessation of cigarette use, in contrast to use of nicotine replacement therapy which has not been found to be continued in an ongoing basis. (ref: Hajek P, Phillips-Waller A, Przulj D, et al. N Engl J Med. 2019
  3. Emerging evidence indicates an association between vaping and elevated blood pressure; the strength of the association is not clear at this time.
  4. The most common pattern of use in Canada is dual use of both vape and combustible tobacco products and therefore smoking cessation strategies should include consideration for both methods of nicotine consumption.
  5. Education and counselling should be provided regarding the risks versus benefits of e-cigarettes in people with stroke, including in younger age groups who have experienced stroke.
2.9 Pregnancy, Oral Contraceptives and Hormone Replacement Therapy
  1. Discussions of pregnancy and implications for stroke recurrence should be included as a routine part of post-stroke management for all female stroke survivors of reproductive age [Evidence Level C].  Refer to CSBPR Secondary Prevention of Stroke during Pregnancy recommendations for additional information
  2. Contraception should be addressed based upon the patients’ fertility and pregnancy plans as well as the stroke mechanism and type [Evidence Level C]. Refer to CSBPR Secondary Prevention of Stroke during Pregnancy recommendations for additional information.
  3. In cases of ischemic stroke, systemic estrogen-containing contraceptives or hormone replacement therapy that can increase the risk of thrombosis should be carefully considered and, in most cases, should be avoided due to an increased risk of stroke [Evidence Level B]. 
  4. Management alternatives, including progesterone-only oral contraceptives, progesterone-only or non-hormonal intrauterine devices, or barrier contraception can be considered in consultation with a provider experienced with contraceptive methods [Evidence Level C].  
  5. Estrogen-containing oral contraceptives or hormone replacement therapy should be discouraged or discontinued in female patients with transient ischemic attack or ischemic stroke [Evidence Level B]. Management alternatives should be considered in these patients [Evidence Level C]. Refer to SOGC.
  6. NEW for 2020:   Contraceptive management alternatives to estrogen containing hormonal contraceptives should be considered for women with a history of migraine with aura [Evidence Level C], especially if they are also current tobacco smokers [Evidence Level B]. (ref: ACOG 2019; McClester 2013)
  7. Hypertensive Disorders of Pregnancy:  Discussion on the use and dose of ASA to reduce the risk of a hypertensive disorder of pregnancy (HDP) should be individualized based upon a woman’s risk of HDP (i.e., women with a prior ischemic stroke, prior HDP or other risk factors) and in consultation with obstetrical care providers [Evidence Level C]. Refer to CSBPR  Stroke during Pregnancy recommendations for additional information.
  8. Invitro Fertilization:  For women who have had a cerebral event and are considering invitro fertilization, provide counselling and education about risks of fertility therapy including the potential risk of hyperstimulation, and monitor for complications assuming all other stroke in the young management plans followed and optimized [Evidence Level C].

Refer to Hypertension Canada 2020 recommendations Section 3 for additional information on hypertension in pregnancy. Refer to Society of Obstetricians and Gynecologists current guidelines.

2.10 Adherence to individual prevention plans
  1. At each healthcare encounter, discuss and document patient adherence to their prescribed secondary prevention treatment plans (pharmacotherapy and lifestyle changes), explore and address non-adherence, and provide counselling and engage in joint goal setting to encourage adherence and persistence with treatment [Evidence Level C].

2.11 Emerging Risk Factors

Influenza infection, vaccination, and stroke risk 

  1. Influenza vaccination is recommended as it has been shown to be associated with a decreased risk of stroke or cardiovascular events, particularly in patients with pre-existing cardiovascular risk factors [Evidence Level B]. 

2.12 Air pollution and stroke risk
  1. Counsel individuals regarding long-term exposure to air pollutants, particularly avoiding or minimizing exposure to particulate matter ≤ 2.5 μm in diameter, which may be associated with an increased risk of stroke and cardiovascular disease [Evidence Level B].
Rationale +-

A healthy lifestyle reduces the risk of an initial stroke and the risk of a subsequent stroke for patients with a prior stroke. Hypertension is the single most important modifiable risk factor for stroke. Current research reports estimate that reducing sodium in foods would abolish high blood pressure for almost one in three Canadians. Most of the sodium Canadians consume (77%) comes from processed foods sold in grocery stores and food service outlets. Only about 11% is added during preparation or at the table, with the remainder occurring naturally in foods. Available evidence suggests that lowering sodium consumption to adequate intake levels could reduce the incidence of stroke and heart disease by as much as 30 percent and has a significant impact on lowering blood pressure. Data from Global Burden of Disease Study (Feigin et al. 2016) estimated that in Canada, 12.6% of the stroke burden was attributed to diets high in sodium. 

The evidence for the benefits of exercise in reducing the risk of stroke and other vascular diseases has increased considerably in the past several years.  The 2020 Canadian 24-hour Movement Guidelines for Adults implement a balanced approach to including exercise, sleep and reduced sedentary behaviours as part of their new recommendations, as these have all been associated with improved mortality and morbidity in adults (Ross et al, 2020).  

There is a growing concern for obesity in the Canadian population, especially in younger adults and this must be addressed with all patients with stroke or at risk.  Data from Global Burden of Disease Study (Feigin et al. 2016) reported that in Canada 28.4% of the stroke burden was attributed to a high BMI.  Obesity may be result of an obesogenic food environment which includes frequent high exposure to high fat, sugars, calories, etc.  Saturated fat increases LDL-cholesterol levels in the blood. High LDL-cholesterol is a risk factor for heart disease and stroke. Replacing saturated fats with mono- and poly-unsaturated fats decreases LDL-cholesterol. It is estimated that Canadians consume approximately 10% of their total calorie intake from saturated fats. Highly processed foods are a major source of saturated fat in the Canadian diet. These highly processed foods are also high in calories, sodium, and free sugars, and can be high in other types of unhealthy fats like trans fatty acids (trans fats). Canadian estimates have been reported for burden attributed to several stroke risk factors, including for tobacco use (13% of stroke burden), alcohol use (7.7%), low physical activity (10.9%), low fruit intake (20.4%), low vegetables intake (19.5%).

The Quality of Stroke Care in Canada stroke audit report found that among all Canadians who experienced a stroke in 2008-09, 41% were current smokers, and more prominent in younger adult stroke patients (less than 49 years old). The InterStroke study reported that current smokers had increased risk of stroke, with the impact greater on ischemic stroke compared to hemorrhagic stroke, and this risk increased with the number of cigarettes smoked per day. Also, the significant impact of smoking on stroke was second only to hypertension.  The 2019 Canadian Community Health Survey has reported that approximately 14.8% of people in Canada (age 12+) are current smokers, and a large proportion has been shown to be willing to make a quit attempt. Health care providers have an important role to play in assisting individuals to quit smoking.  Moreover, even brief interventions by providers are known to be effective in increasing the likelihood of a quit attempt by a person who smokes.  Clinical practice guidelines are known to be an important and effective provider tool to close the gap between recommended care and actual care provided.  Smoking cessation has been found to reverse/reduce stroke risk as duration of being smoke-free increased. 

Female patients who have had a stroke are at additional risk for recurrent stroke if they continue to smoke and are taking oral contraception or estrogen-based hormone replacement therapy.  Research has also demonstrated an increased risk of thrombosis with estrogen-based hormone therapy (both oral contraceptives and hormone-replacement therapy).  
People with stroke, their family members and caregivers expressed the need to have risk factor management information early on after the stroke occurs.  Many of these individuals have expressed concerns that they did not receive this information until significant time had passed or had not received this information at all. This issue highlights a potential disconnect between people with stroke and their health care team after transition to living in the community, and potential disconnect between their primary healthcare provider and the other health professionals involved in their care, such as the stroke expert and rehabilitation team members. 

People with stroke have also voiced the difficulty in managing and tracking lifestyle behaviour changes and knowing what targets are appropriate for them. Education on how to manage these risk factors is essential along with easy-to-use tools to support their efforts. People with stroke also emphasized the need to individualize the interventions to be able to successfully work on these risk factors.  Some people with stroke have difficulty with physical exercise due to other conditions and needed their exercise routine individualized to meet their unique needs. Feedback from people with stroke also included the need for individualization of strategies that incorporate other health issues that may be experiencing, as multimorbidity is becoming increasingly common among people with stroke (Heart & Stroke Disconnected Report, 2019).

System Implications +-
  1. Health promotion efforts that contribute to the prevention of stroke in all communities (integrated with existing chronic disease prevention initiatives) must be established.

  2. Coordinated and comprehensive stroke prevention should be offered by primary care providers, and a mechanism in place to ensure that stroke risk is addressed during encounters with healthcare professionals throughout the continuum of care.

  3. Improved communication and transition planning between all stages and settings of care and ensuring that primary care team members are fully informed on the goals of care, prevention therapies initiated by the healthcare providers during first assessments (e.g., in the emergency department), follow-up appointments for further investigations and longterm management.  

  4. Public and population health focus on cerebrovascular health for paediatric cases focus on risk reduction through diet, - including limited saturated fat, sodium and sugar intake, - physical activity, non-smoking, avoidance of drugs that increase stroke risk. 

  5. Regional, national, and international efforts to reduce sodium intake by working with governments and changing the food supply in both the food retail and restaurant sector are required.

  6. Increase public awareness and knowledge about the risks of sodium through targeted and population-based campaigns. School programs which teach food literacy including cooking from scratch using whole, minimally processed foods. Promote mandatory front of package nutrition labelling to help increase public awareness, knowledge, improve decision making and encourage product reformulation.

  7. Local, regional, and federal food strategies which improve access to and affordability of whole unprocessed foods in all communities.

  8. Access to risk factor management programs (such as hypertension and smoking cessation programs) in all communities, primary healthcare settings and workplaces

  9. Improved best practice cessation support through pharmacotherapy, nicotine replacement therapy and behavior counselling. Access to these types of interventions can be facilitated through a universal pharmacare program.

  10. Government action at all levels of government to reduce tobacco use. Consider WHO MPOWER tobacco control strategy as a framework. (https://www.who.int/tobacco/mpower/en) which emphasizes in the guiding principles that smokers should be granted access to smoking cessation support without financial burdens.                            

  11. Coordinated efforts among stakeholders such as the Heart and Stroke Foundation, public health agencies, ministries of health and care providers across the continuum to produce patient, family and caregiver education materials with consistent information and messages on risk factor management.

  12. Coordinated processes for ensuring access to and awareness of educational materials, programs, activities and other media related to risk factor management by healthcare professionals, patients and caregivers, including promotion of educational material and effective dissemination mechanisms.

  13. Improved access to pharmaceuticals and behavior counselling for smoking cessation through private and public drug coverage plans.

  14. Government action at all levels of government to reduce tobacco use. 

  15. Government regulation of e-cigarettes, including flavours restrictions and nicotine limits, taxation, raising the legal of purchase to 21 years, prohibiting the use of e-cigarettes in workplaces and public places where smoking is banned by law and e-cigarette sales in locations where tobacco sales are banned.

  16. Access to culturally and ethnically appropriate educational resources in multiple languages as well as special resources for patients with aphasia. 

  17. Increased infrastructure investments in communities that facilitate physical activity. This should include recreational infrastructure (such as recreation centres, arenas) and active transportation infrastructure (e.g., sidewalks, bike paths).

  18. Access to healthy living programs, educational materials and healthcare professionals for persons living in rural and remote locations, including innovative use of technology and virtual healthcare.

  19.  Increased measures to reduce air pollution.

  20. Integration of air pollution considerations into disease management approaches, for example through the use of air quality indices.

  21. Access to education and efforts to raise awareness on the cardiovascular benefits of clean air.

  22. If the community doesn’t have regular access to rehabilitation services (such as physiotherapy), could there be encouragement to connect to another facility that provide the service.  What level of supervision is available – communities may have other options.

Performance Measures +-
  1. Proportion of patients with major risk factors for stroke, including hypertension, obesity, hyperlipidemia, diabetes, atrial fibrillation, smoking, and physical inactivity. (KQI)
  2. Annual occurrence rates for stroke in each province and territory by stroke type (KQI).
  3. Proportion of acute stroke and transient ischemic attack patients who are discharged alive from an emergency department or an inpatient stay and then readmitted to hospital for any cause within 7 days of index acute stroke discharge. (KQI)
  4. Stroke mortality rates across provinces and territories, including in-hospital or 30-day rate and one-year rate (KQI).
  5. Percentage of the population who can identify the major risk factors for stroke, including hypertension, sodium intake, diet, weight, exercise, smoking and alcohol intake.
  6. The annual readmission rate for a recurrent stroke or transient ischemic attack event in patients with previous stroke or transient ischemic attack.
  7. Proportion of patients with documented smoking status recorded on patient record.
  8. Proportion of patients with stroke and transient ischemic attack with a history of tobacco smoking who are given smoking cessation advice and counselling during acute hospital stay, inpatient and outpatient rehabilitation, and during secondary prevention visits.
  9. Proportion of stroke and transient ischemic attack patients who participate in a smoking cessation program who are smoke-free at 6 months, one year and two years.

Measurement notes

  • For performance measures 1, 2 and 3: self-reported data can be extracted from provincial and national health surveys. These data should be standardized to the most current national census data for age and sex.

  • Performance measures 4: administrative data are available at the local, provincial and national levels.

  • Mortality rates should be risk adjusted for age, sex, stroke severity and comorbidities.

Implementation Resources and Knowledge Transfer Tools +-

Health Care Provider Information

Patient Information

 

Summary of the Evidence +-

Lifestyle and Risk Factor Management Evidence Table and Reference List

Lifestyle and Risk Factor Management


Diet

Adherence to several dietary eating patterns has been examined in the context of stroke risk. Among them, the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean Diet are two of the most recognized. Feng et al. (2018) included the results of 12 prospective cohort studies including 548,632 participants. During follow-up, which ranged from 5.7 to 24 years, higher adherence to the DASH diet significantly reduced the risk of stroke (RR=0.88, 95% CI 0.83-0.93). Each 4-point increment in DASH score conferred a risk reduction of 4% (RR= 0.96, 95% CI 0.94–0.97) in total stroke events. Larsson et al. (2016) also reported that high adherence to a modified DASH diet was associated with a reduced risk of ischemic stroke, particularly among women. The study included a population-based sample of almost 75,000 individuals without history of stroke, heart disease or cancer, who were followed for an average of 11.9 years. 

A systematic review & meta-analysis conducted by Psaltopoulou et al. (2013), including the results of 11 studies, concluded that high adherence to a Mediterranean diet was associated with reduced risk of total stroke and ischemic stroke (total stroke: RR=0.71, 95% CI 0.57-0.89; ischemic stroke: RR=0.52, 95% CI 0.28-0.96). One of the key components of the Mediterranean diet is olive oil, which has been shown to decrease the risk of cardiovascular diseases. The Prevención con Dieta Mediterránea Trial (PREDIMED) evaluated the benefits of 2 types of Mediterranean diet, increased consumption of extra-virgin olive oil or mixed nuts, as compared to a control group in which participants were advised to follow a low-fat diet (Estruch et al. 2013). After a median follow-up of 4.8 years, the two Mediterranean diets were associated with 30% reductions in the primary outcome, a composite of myocardial infarction, stroke, or death from cardiovascular causes. Most of this protective effect was driven by a reduction in stroke events. The results of the PREDIMED study were included in a systematic review (Martınez-Gonzalez et al. 2014) specifically examining the protective effect of olive oil. For each 25 g/day increase in olive oil consumption there was a significant reduction in the risk of stroke (RR=0.76, 95% CI 0.67-0.86, p<0.001). 

Sodium
It is well documented that a consistently high dietary sodium intake is associated with elevated blood pressure, while modest decreases may lower blood pressure and reduce stroke risk. Mozaffarian et al. (2014) used various data sources and national-level surveys to estimate that, in 2010, 99% of all adults in the world exceeded the WHO recommendations of 2.0 g/day. Worldwide, the mean global level of sodium intake was 3.95 g/day. An estimated 1.65 million deaths were attributed to sodium intake above the recommended level, of which 685K (42%) were caused by stroke. In one of the PURE publications, Mente et al. (2018) estimated that for each 1-gram increase in estimated sodium intake, systolic BP increased by 2·86 mm Hg (95% CI 2·12–3·60, p<0·0001). Feigin et al. (2016) estimated that 22.6% of the global stroke burden was attributed to diets high in sodium (12.6% in Canada). In a Cochrane review, He et al. (2013) examined 34 RCTs (n=3,230) comparing the effect of moderately restricted sodium intake (2.3-7.0 g/day or 40-120 mmol/day urinary sodium excretion) for a minimum of 4 weeks with usual intake over the same duration. The mean difference in sodium intake between groups was 1,955 mg per day, which was associated with a significant decrease in SBP (-4.18 mm Hg, 95% CI -5.18 to -3.18; p<0.001) and DBP (-2.06 mm Hg, 95% CI -2.67 to -1.45; p<0.001). Results were similar in a subgroup analysis of 22 trials that included 990 patients with hypertension. Reduced intake was associated with a significant reduction in both SBP (-5.39 mm Hg, 95% CI -4.15 to -6.62; p<0.001) and DBP (-2.82 mm Hg, 95% CI -2.11 to -3.54; p<0.001). 

Physical Activity
Physical activity (PA) is an important modifiable lifestyle factor that can play a protective role in both primary and secondary prevention of stroke. Using data from 188 countries, obtained from the Global Burden of Disease Study, Feigin et al. (2016) reported that 7.7% of the global stroke burden was attributed to low physical activity. In Canada, the estimate was 10.9%. The results from several large cohort studies provide some estimates of the magnitude of the protective effect of physical activity. In one of the PURE publications, Lear et al. (2017) included 130,843 participants without pre-existing cardiovascular disease, aged 35-70 years (mean age 50.2 years). After an average of 6.9 years of follow-up, the risk of all-cause mortality and major cardiovascular disease was reduced significantly among persons who engaged in high levels of moderately intense physical activity (>750 minutes/week) and moderate amounts (150-750 minutes /week) compared with those who engaged in low levels of physical activity (<150 minutes/week). In phase 1 of the INTERSTROKE case-control study, O’Donnell et al. (2010) reported that regular physical activity was associated with a reduced risk of total and ischemic stroke (total stroke: OR=0.69, 99% CI 0.53-0.90, ischemic stroke: OR=0.68, 99% CI 0.51-0.91). In phase 2 of the INTERSTROKE study (O’Donnell et al. 2016), the pattern of results was similar. 

Weight
There is an increased risk of stroke associated with being overweight or obese. Feigin et al. (2016) reported that 23.5% of the global stroke burden was attributed to high BMI (>23.0), while in Canada the estimate was 28.4%. Twig et al. (2016) included 2.3 million adolescents who were followed over time to examine the association between BMI and cardiovascular death. During 42,297,007 person-years of follow-up, there were 32,127 deaths, including 528 from stroke. Compared with the reference category (BMI percentile 5th-24th), the risk of death from stroke was significantly increased in the 3 highest BMI categories, in which the median BMI (men and women combined) were 24.4, 26.6 and 31.0, respectively (75th-85th: HR=1.42, 85th-94th: HR=1.81, ≥95th: HR=2.64). Saito et al. (2011) compared stroke risk in 32,847 men and 38,875 Japanese women, aged 45–74 years with no history of cardiovascular disease, who were of normal weight (BMI 23.0-24.9 kg/m2) with persons who had high BMIs (27.0 to 29.9 and ≥ 30.0). The risk of stroke significantly increased with increasing BMI (HR= 1.09 and 1.25 for men, and HR=1.29 and 2.16 for women, respectively, relative to healthy weight). In women, a weight increases of greater than 10% over the previous five years was also associated with increased stroke risk. In phases 1 and 2 of the INTERSTROKE case-control study, O’Donnell et al. (2010, 2016) reported that increasing waist-to-hip ratio was associated with increased risk of total stroke, ischemic stroke and hemorrhagic stroke. 

Alcohol Consumption
Evidence from several studies suggest that light to moderate alcohol consumption may reduce the risk of stroke, while excessive consumption may increase risk. In the China Kadoorie Biobank Prospective study (Millwood et al. 2019) included 512,715 adults from 10 areas in China, aged 35-74 years, without known major disabilities, to examine the effect of alcohol consumption on cardiovascular disease risk. Among men, 33% reported drinking alcohol in most weeks, mainly as spirits. Using conventional epidemiological analysis, the risk of stroke was U-shaped, whereby the relative risk of total stroke was 1.23 (95% CI 1.19, 1.27) for non-drinkers, compared with 1.00 (95% CI 0.98-1.03) for occasional drinkers. Among current drinkers, the risks of ischemic stroke, ICH and total stroke were all significantly increased (when intake exceeded 100 g per week). Per each 280 g per week increase in alcohol intake, the risks of ischemic stroke ICH and total stroke were all significantly increased (RR= 1·28, 95% CI 1·19–1·38; HR= 1·59, 95% CI 1·37–1·85 and RR= 1·35, 95% CI 1·27–1·44, respectively). In contrast, there was no U-shaped pattern using genotype-predicted mean alcohol intake, whereby the risk of ischemic stroke, ICH and total stroke increased across the whole range of mean alcohol intakes (RR= 1·27, 95% CI 1·13–1·43, RR= 1·58, 95% CI 1·36–1·84 and RR= 1·38, 95% CI 1·26–1·51, respectively). In women, the risks of ischemic stroke, ICH, total stroke, acute myocardial infarction (MI) and coronary heart disease (CHD) were not increased with alcohol consumption in either the conventional analysis, nor genetic analysis, although only 2% of women reported drinking alcohol most weeks. Zheng et al. (2015) pooled the results from 23 cohort studies and found that, compared with the lowest or no alcohol groups, the risk of stroke was not significantly increased in men or women as alcohol consumption increased; rather, the risk of ischemic stroke was lower in men who were light drinkers and for women who were light or moderate consumers. In contrast, using the results from 26 studies, O’Donnell et al. (2010) reported that moderate alcohol consumption (1-30 drinks/month) was associated with reduced risk of ischemic stroke (OR=0.79, 95% CI 0.63-1.00), but with an increased risk of hemorrhagic stroke (OR=1.52, 95% CI 1.07-2.16) compared with never/former drinkers. Binge drinking, or >30 drinks/month, was associated with an increased risk of ischemic and hemorrhagic stroke compared with never/former drinkers. In phase 2 of INTERSTROKE (O’Donnell et al. 2016) low or moderate ETOH intake was associated with significantly higher odds of total and hemorrhagic stroke compared with former/never drinkers, with no risk in the increase of ischemic stroke. 

Recreational Drug Use
The most commonly used illicit drugs associated with increased stroke risk are cocaine, amphetamines, Ecstasy, heroin/opiates, phencyclidine (PCP), lysergic acid diethylamide (LSD), and cannabis/marijuana. These drugs may increase the risk for stroke through a variety of mechanisms, including hypertensive surges, vasospasm, enhanced platelet aggregation, vasculitis, accelerated atherosclerosis and cardioembolism. Using data from 3,307,310 young adults 18-49 years, who were hospitalized between 2007 and 2014 in the USA, and who were current or previous cannabis users, Desai et al. (2019) reported the odds of any stroke and ischemic stroke were increased significantly among cannabis users compared with non-users (adj OR= 1.16, 95% CI 1.14–1.19, p<0.001 and adj OR= 1.41, 95% CI 1.31–1.51, p<0.001), among 34,857 (1.1%) hospitalizations that were stroke related. In contrast to these findings, Luis et al. (2020) reported that recent marijuana use was not an independent predictor of acute ischemic stroke.

Cheng et al. (2016) examined whether recent cocaine use increased the risk of stroke. Cocaine use within 24 hours of the reference date was associated with a significantly increased risk of ischemic stroke (OR=6.4, 95% CI 2.2-18.6, p<0.001), as was frequent use (≥1/week; OR=2.6, 95% CI 1.6-4.3, p<0.001). An increased risk of stroke associated with cocaine use was also reported by Westover et al. (2007) in a cohort of patients recently discharged from hospital. Previous cocaine use was associated with an increase in the risk of both hemorrhagic and ischemic stroke (OR=2.33, 95% CI 1.74-3.11and OR=2.03, 95% CI 1.48-2.79, respectively). In the same study, amphetamine use was also associated with an increase in the risk of hemorrhagic stroke (OR=4.95, 95% CI 3.24-7.55) and an increased risk of hemorrhagic stroke resulting in death (OR=2.63, 95% CI 1.07-6.50). 

Smoking
Smoking is a major risk factor for cardiovascular disease, including stroke and heart attacks. Smokers are significantly more likely to have a stroke compared with non-smokers.  It has been estimated that globally, 20.7% of the stroke burden is attributable to tobacco use (Feigin et al. 2016). A systematic review & meta-analysis (Peters et al. 2013) reported sex-specific risks of current smokers vs. non-smokers including the results from 81 prospective cohort studies, which represented 3,980,359 persons. The prevalence of current smoking ranged from 8% to 59% in men and from 1% to 51% in women. Most studies reported higher smoking rates among men. Over the duration of follow up, which ranged from 6-40 years, there were 42,401 strokes.  The risk of stroke was higher in current smokers compared with non-smokers in both women: (RR=1.83, 95% CI 1.58-2.12) and men (RR=1.67, 95% CI 1.49-1.88). The risk of stroke was also higher in former smokers compared with never smokers (women: RR=1.17, 95% CI 1.12-1.22; men: RR=1.08, 95% CI 1.03-1.13). The risk of hemorrhagic, but not ischemic stroke, was significantly increased in women who smoked compared with men who smoked (RR=1.17, 95% CI 1.02-1.34, p=0.02). In phase I of the INTERSTROKE study (O’Donnell et al. 2010), there was an increased risk of all stroke (OR=2.09, 99% CI 1.75-2.51), ischemic stroke (OR=2.32, 99% CI 1.91-2.81) and hemorrhagic stroke (OR=1.45, 99% CI 1.07-1.96) associated with current smoking. In phase 2 of the study (O’Donnell et al. 2016), which included a larger sample size (26,919), the risk of ischemic stroke was higher among current smokers compared with the risk of hemorrhagic stroke (OR=1.93, 99% CI 1.69-2.21 vs. OR=1.14, 99% CI 0.95-1.36). The risk of both stroke types increased with the number of cigarettes smoked daily. 

Both pharmacological agents and behavioural intervention strategies have proved effective as smoking cessation interventions. A Cochrane review (Hartmann-Boyce et al. 2018) included the results of 136 RCTs (n=64,640) of current smokers who were people motivated to quit. Trials compared nicotine replacement therapy (NRT) including chewing gum (n=56), transdermal patches (n=51), nasal (n=4) or oral spray (n=5), inhalators and tablets or lozenges (n=8), and combinations of NRTs to placebo or no treatment. Overall, the use of all forms of NRT was associated with a significantly increased likelihood of successful smoking cessation (RR=1.55, 95% CI 1.49 to 1.61), with little effect of type of NRT, while intensive behavioural support was not found to be essential for NRT to be effective. Another Cochrane review (Stead et al. 2015) examined the use of behavioral therapy support as an adjunct to pharmacotherapy and reported that more intensive behavioural support was associated with a better chance of long-term abstinence from smoking when combined with pharmacotherapy, as compared to pharmacotherapy combined with less intensive behavioural support (RR= 1.17, 95% CI 1.11 to 1.24).
An earlier Cochrane review of reviews examined the effectiveness of pharmacological treatments to promote smoking cessation in adults included the results of 12 Cochrane reviews, aggregating the results from 267 RCTs, 101,804 participants (Cahill et al. 2013). Treatments evaluated included nicotine replacement products, such as gums, transdermal patches, nasal sprays or inhalers, the non-tricyclic antidepressant, bupropion and varenicline, a nicotinic receptor partial agonist. Compared with placebo, all forms of therapies significantly increased the odds of sustained smoking cessation (odds ratios ranged from 1.82-2.88). Varenicline was superior to single forms of nicotine replacement therapy (OR= 1.57, 95% Credible interval [Cred I] 1.29 to 1.91) and was also superior to bupropion (OR= 1.59, 95% CredI 1.29 to 1.96). The odds of serious adverse events (chest pains and heart palpitations) associated with nicotine replacement therapy were significantly increased (OR= 1.88, 95% CI 1.37- 2.57). The most common side effects associated with bupropion were insomnia, occurring in 30% to 40% of patients, dry mouth (10%) and nausea. The main serious adverse event was seizures. The main adverse event for varenicline was mild-moderate nausea, which subsided over time and was rarely reported. Typical drop-out rates due to adverse events ranged from 7% to 12%. 
Mullen et al. (2016) examined the use of the Ottawa Model’ for Smoking Cessation (OMSC), a systematic approach to tobacco dependence treatment delivered within healthcare settings, which included in-hospital counselling, and pharmacotherapy follow-up support post hospitalization. At one and two years, the cumulative incidences of death and all-cause re-hospitalizations, and smoking-related readmissions were significantly lower in the OMSC group. All-cause emergency department visits were also significantly reduced in the intervention group. In this trial patients in the control group were randomized to usual care, which generally consisted of a self-help pamphlet.

The use of electronic cigarettes (e-cigarettes) has increased in recent years. They may be used as an alternative to conventional cigarettes or as an aid in smoking cessation programs. The use of e-cigarettes has been shown to significantly reduce the use of conventional cigarettes, compared with nicotine-replacement products (Hajek et al. 2019).  In this RCT that randomized 886 adult smokers to receive nicotine patches or e-cigarettes, provided for up to three months, the one-year abstinence rate was significantly higher in the e-cigarette group (18.0% vs. 9.9%; RR=1.83; 95% CI, 1.30 to 2.58; p<0.001). A Cochrane review (Hartmann-Boyce et al. 2016) included the results of two RCTs and 11 cohort studies including participants who were current smokers who may/may not have been motivated to quit. Participants using nicotine e-cigarettes were more likely to quit smoking compared with those using placebo e-cigarettes (RR=2.29, 95% CI 1.05-4.96, p= 0.037). Among 657 participants who were current smokers (>10 cigs/day) and who wanted to quit smoking, persons randomized to an e-cigarette group had reduced their mean daily tobacco use significantly more compared with persons in the nicotine patch group or the placebo e-cigarette group (1.9 vs 9.7 vs. 7.7 cigs/day, p=0.002); however, the superiority of nicotine e-cigarettes over nicotine patches or placebo e-cigarettes could not be established due to lower than expected quit rates (10% was anticipated)(Bullen et al. 2013). Nevertheless, the safety of e-cigarettes remains unclear. There is evidence that the use of e-cigarette devices may expose the user to substances which may increase vascular inflammation and cause the development of pulmonary changes.

Birth Control/Hormone Replacement Therapy
Women taking oral contraceptive or hormone replacement therapy (HRT) may be at an increased risk of stroke. In a Cochrane review (Roach et al. 2015) that included the results of 24 studies, combined oral contraception users were found to be at increased risk of MI or ischemic stroke (RR=1.6, 95% CI 1.3-1.9), MI (RR=1.6, 95% CI 1.2 to 2.1) and ischemic stroke (RR=1.7, 95% CI 1.5 to 1.9) compared with non-users. The risk of both events increased with increasing doses of estrogen. In a large cohort study including the results of over 1.6 million women between the ages of 15 and 49 years, Lidegaard et al. (2012) reported that current use of ethinyl estradiol at doses of 20 to 50 μg was associated with an increased risk of thrombotic stroke, compared with nonusers, while current use of progestin only was not.

Hormone replacement therapy was not found to significantly increase the risks of all-cause mortality, nonfatal MI, angina or need for revascularization when used for primary or secondary CVD prevention in a Cochrane review (Boardman et al. 2015); however, the risk of stroke was increased significantly (RR=1.24, 95% CI 1.10 to 1.4), as were the risks of venous thromboembolism and PE (RR=1.92, 95% CI 1.36 to 2.69 and RR=1.81, 95% CI 1.32 to 2.48, respectively). Similarly, Renoux et al. (2010) reported that, compared to non-users, women using oral HRT within the previous year had a higher risk of stroke (RR= 1.28, 1.15-1.42). Use of oral HRT for >1 year was associated with increased risk of stroke (RR=1.35, 95% CI 1.20-1.52), but not for a duration of ≤1 year. High dose transdermal patch use was associated with an increased risk of stroke (RR=1.89, 95% CI 1.15-3.11), although low- dose patches were not (RR=0.95, 0.75-1.20). The risk of stroke was also significantly increased in the Women's Health Initiative, among women in the combined estrogen/progesterone group compared with placebo (HR=1.31, 95% CI 1.02-1.68).

Compliance with Secondary Prevention Measures
Since rates of recurrent stroke, and other vascular disorders are known to be significantly elevated during the first four years after hospitalization for first stroke (Feng et al. 2010), and potentially modifiable risk factors represent approximately 90% of the population-attributable risk for stroke (O’Donnell et al. 2016), secondary prevention measures represent an important opportunity to reduce the risk. While the effectiveness of many of the interventions designed to prevent recurrent stroke, including medications associated with hypertension, diabetes, dyslipidemia and cardiac conditions (described in other sections of the guidelines) are well-established, their protective effects are diminished by poor compliance. Efforts aimed at improving compliance through behavioral or educations interventions have been disappointing in several recent RCTs. Fukuoka et al. (2019) reported no difference between groups in mean Framingham risk score after a 6-month nurse-led disease management program (DMP) or usual care. A Cochrane review (Bridgwood et al. 2018), which included the results from 42 trials examining interventions to improve modifiable stroke risk factors, also reported no differences in blood pressure, serum cholesterol, HbA1c or BMI between intervention and usual care groups at the end of treatment. 

Emerging Risk Factors
i) Influenza
Seasonal influenza has been shown to increase the risk of stroke and heart disease (Kwong et al. 2018, Boehme et al. 2018). In a case-crossover study involving 36,975 patients hospitalized for ischemic stroke, the odds of stroke were increased by 288% given prior influenza exposure within the previous 15 days, decreasing to 168% given exposure within the previous 60 days. The risk was highest among persons aged 18-45-years with influenza exposure within the previous 15 days (OR= 9.28, 95% CI 1.72–50.2). Field et al. (2004) examined data from hospital stroke admissions in a large Canadian city from 1994-2001, and reported that during that period, as influenza rates increased, so did stroke rates. The slope of the β co-efficient for total stroke was 0.63 (95% CI 0.58-0.67). 

The influenza vaccine can reduce the added risk of stroke. Tsivgoulis et al. (2018) reported the risk of ischemic stroke was reduced significantly among persons who received influenza vaccine, a portion of whom had a previous stroke (RR=0.87, 95% CI 0.79-0.96, p=0.004). Lee et al. (2017) also reported the overall risk of stroke was reduced significantly in vaccinated persons (OR= 0.82; 95% CI 0.75–0.91; p < 0.001). Decreased risks of cardiovascular events and deaths associated with influenza vaccination has been reported elsewhere (Clar et al, 2015, Udell et al. 2013).

ii) Air Pollution
Pollutants such as particulate matter (PM), ozone, sulphur dioxide, carbon monoxide, nitrogen dioxide, and nitrogen oxide, represent a significant risk to health. For example, long-term exposure to PM with an aerodynamic diameter of ≤ 2.5 μm (PM 2·5) contributed to 4.2 million deaths and to a loss of 103.1 million disability-adjusted life years (DALYs) in 2015, representing 7.6% of total global deaths and 4.2% of global DALYs (Cohen et al. 2017).  However, in 2015, data from the same study revealed that Canada was among the countries with the lowest exposure to PM2·5 with concentrations ≤8·0 μg/m³. A recent systematic review (Yang et al. 2019), included the results from 35 studies, of which 17 were from the USA and 6 were from Canada. Each 10 μg/m3 increase in PM2.5 was associated with a significantly increased risk of stroke (RR=1.12, 95% CI 1.02–1.16), and stroke mortality (RR=1.11, 95% CI 1.07–1.14). Data from 2,145,400 persons included in the 1991-2001 Canadian mortality follow-up study indicated the risks of mortality associated with long-term exposure to PM 2.5 significantly increased the risks of cardiovascular diseases, circulatory diseases, and ischemic heart disease, while the risk of mortality-related cerebrovascular disease, was not (Crouse et al. 2012).

 

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