Stroke is the second leading cause of death and disability in the world.1,2 Over last several decades the burden of stroke in the world has shifted from developed to developing countries.3 Now, 75% of all stroke deaths and 81% of the total disability adjusted life years (DALYs) lost due to stroke occur in developing countries.3 This shift in the burden from the developed to developing countries is thought to be driven by the ageing of population, population growth, and changing patterns of diseases due to changes in risk factors and differences in socioeconomic status and health care.4,5 Stroke, therefore, has emerged as a major public health priority in developing countries.
Challenges to providing healthcare for stroke
While the burden of stroke has increased in developing countries the healthcare services have not caught up. The challenges to provide healthcare services for stroke in developing countries include lack of awareness about stroke and its risk factors, lack of economic resources and publicly-funded well functioning healthcare systems for primary and secondary prevention, lack of ambulance services and facilities for acute stroke management, unaffordable cost of t-PA, lack of rehabilitation facilities, preference for alternative and complementary medicines over modern medicines and poor secondary prevention.6 These challenges often lead to worse outcomes after stroke and studies in some regions of Gambia and India have reported 30-day case fatality as high as 40%.7,8 Also, a large percentage of people in developing countries live in rural areas where healthcare is not accessible. Authors of several studies have shown high mortality and prevalence of stroke in rural regions of developing countries.9–11 The poor population in developing countries are often affected by stroke and stroke perpetuates poverty in these people. Attempts are being made in developing countries to improve stroke services, but these are in very early stages.12 Therefore, urgent attention is needed to reduce the burden of stroke in developing countries.
Need for an emphasis on prevention
Stroke is preventable. While attempts should be made to improve acute stroke care services in developing countries, data from the developed countries suggests that a strong emphasis on prevention would be needed to reduce the burden of stroke. From a public health point of view, preventive measures to reduce the risk of stroke would provide additional cross-cutting benefits. For example, reducing blood pressure or cholesterol using pharmacological and lifestyle interventions would also reduce mortality due to other chronic diseases such as coronary artery disease, chronic kidney disease and reduce the risk of dementia.
Risk factors for stroke in developing countries
Are the risk factors for stroke different in developing countries than in developed countries? INTERSTROKE, the largest international case-control study on stroke which included participants from developing countries in Africa, Asia, America and the Middle East provided important insights in this regard.13 The study identified ten modifiable risk factors for stroke and calculated their population-attributable risk which is the percentage of stroke cases that would not occur if the risk factor is eliminated (Table 1). The risk factors identified were hypertension, lack of physical activity, abnormal lipids, unhealthy diet, abdominal obesity, psychological factors, current smoking, cardiac causes, alcohol consumption and diabetes. Together, these ten risk factors accounted for close to 90% risk of stroke. Although there were geographical variations in the extent of the risk (odds ratios) due to each risk factor, the overall direction of association of risk factors with the risk of stroke was similar except for diet in south Asian countries. A recent large case-control study from Africa also confirmed the association of risk factors identified in the INTERSTROKE study with the risk of stroke.24 Therefore, by and large the risk factors for stroke seem to be similar in the developing and developed countries. Few additional stroke risk factors were identified by the Global Burden of Disease study.25 These include low glomerular filtration rate, ambient and household air pollution and lead exposure.
Table 1.
Risk factor | Population attributable risk of stroke (%) | Preventive strategies for stroke being used or trialled in developing countries |
---|---|---|
High blood pressure | 47.9 | Mass screening and treatment of hypertension,14,15 community-based hypertension control using community health workers16,17, polypill18, community-based lifestyle change program19, mass health promotion strategies19–21 |
Physical inactivity | 35.8 | Mass health promotion strategies19–21 |
Dyslipidemia (Apolipoprotein Apo B/ApoA1 ratio) | 26.8 | Polypill18, mass health promotion strategies19–21 |
Diet risk score (unhealthy cardiovascular diet) | 23.2 | Mass health promotion strategies19–21 |
Abdominal obesity | 18.6 | National program targeting obesity22 |
Psychosocial factors | 17.4 | - |
Current smoking | 12.4 | Mass health promotion strategies19–21, anti-tobacco measures by the state21,23, |
Cardiac causes | 9.1 | Polypill18, national programs to control cardiac diseases22 |
Alcohol consumption | 5.8 | Mass health promotion strategies19–21 |
Diabetes | 3.9 | National programs to control diabetes22 |
In developing countries, the other stroke risk factors that operate include infections (e.g. tuberculosis, syphilis, Human Immunodeficiency Virus infection, malaria, schistosomiasis, gnathostomiasis, rheumatic heart disease, infective endocarditis, mycotic aneurysms), sickle cell disease, Takayasu's disease, snake bites and scorpion sting.26 Many of these risk factors are being controlled due to gradually improving awareness, healthcare services, screening for those with rheumatic heart disease and sickle cell disease in the school health programs as well as mass infectious disease eradication programs and likely to contribute to a smaller number of stroke cases at the population level. However, more progress needs to be made in Africa where these risk factors are still prevalent. For example, in the INTERSTROKE study the ten risk factors discussed above contributed to 82% of the total risk of stroke as compared to 90% or more in the other continents.13
Strategies for stroke prevention
Two major strategies have been proposed for reducing risk of cardiovascular diseases. The first one is the high risk strategy and the other one is the mass strategy.27
High risk strategy
The high risk strategy identifies those at a higher risk of developing a disease. For stroke prevention, those with modifiable risk factors (Table 1) can be targeted for primary prevention of stroke under the high risk strategy. Additionally, a new approach of prevention based on projected overall cardiovascular disease (CVD) risk has been proposed.28,29 This approach posits that an individual may not have a specific disease or a health condition e.g. hypertension or diabetes but may have a higher overall cardiovascular risk due to presence of multiple risk factors such as pre-hypertension and dysglycemia which do not meet treatment thresholds as per the current standards of care. The support for this argument comes from the observation that cardiovascular risk increases linearly above the systolic blood pressure (SBP) of 115mm Hg.30 The prevalence of individuals with higher cardiovascular risk could be quite high in communities. For example, in the INTERHEART, a case control study conducted in 52 countries, which included developing countries, 99% of the control subjects had at least one cardiovascular risk factor.31 Based on these findings it is proposed that preventive approach based on CVD risk needs to be applied to a larger segment of population.
The interventions under the high risk strategy can be classified as those related to changes in lifestyle and those related pharmacological treatment.
Lifestyle change
Most of the clinical guidelines on prevention of cardiovascular diseases focus on individual patient recommendation and emphasize lifestyle change as the first line prevention strategy. Evidence from cohort and interventional studies supports the role of reduced salt intake, increased fruit and vegetable consumption, physical activity, weight loss, tobacco cessation, limited alcohol intake and management of psychosocial stress in reducing cardiovascular risk.32 Therefore, such measures need to be emphasized to prevent stroke in developing countries as well. A recent cluster randomised controlled trial from Nepal showed that lifestyle change program implemented through community health workers successfully reduced blood pressure demonstrating the feasibility of this approach.33 However, one of the major limitations of individual-based lifestyle and behavioural change approach is that it is difficult to sustain34 and scale. The emergence of global epidemic of obesity highlights the limitations of individual-based preventive strategies.
Pharmacological interventions
Hypertension is the leading risk factor for stroke (Table 1) and its control remains one of the most effective interventions to reduce the risk of stroke. Screening for hypertension at population-level and making treatment available and affordable has resulted in reduced stroke incidence, prevalence and mortality in Japan and Taiwan.14,15,35 Shortage of doctors in developing countries can create a barrier to screening and treatment of hypertension but the emerging evidence from randomised controlled trials from Argentina, China and India suggests that community-level interventions involving community health workers can lead to improved hypertension control.16,17
Under the CVD risk reduction approach, use of medicines to lower blood pressure and lipids along with use of anti-platelet agents has been suggested. Several recent randomised controlled trials show evidence to support this strategy. In the SPRINT trial, targeting systolic blood pressure (SBP) to a lower threshold of 120mm Hg compared to the standard threshold of 140mm Hg in those with increased cardiovascular risk reduced the risk of a composite primary outcome which included stroke.36 This approach also reduced the risk of death. HOPE-3 trial also showed a beneficial effect of cholesterol lowering37, cholesterol and blood pressure lowering38 but not blood pressure lowering alone39 on the risk of developing stroke in those with an intermediate risk of cardiovascular diseases. Furthermore, a recent meta-analysis using individual participant data from 47,872 participants from 11 trials in the Blood Pressure Lowering Treatment Trialists' Collaboration from 1995 to 2013 also showed that compared to treating everyone with SBP ≥150 mmHg or ≥ 140mm Hg, a CVD risk reduction strategy could prevent 16% or 3.1 % more cardiovascular events respectively for the same number of persons treated.40 There is some criticism of this strategy that it will medicalize prevention. Also, there could be several practical difficulties in the use of CVD risk scores in developing countries, particularly in rural areas. These include lack of risk scores which are calibrated for the local population41 and a need for laboratory tests for some risk scores. However, one study conducted in Bangladesh, Guatemala, Mexico, and South Africa showed that community health workers could successfully categorize cardiovascular risk using a risk score which does not need laboratory tests.42 Another potential limitation of this approach could be that people in rural areas of developing countries may find it hard to understand the concept of CVD risk as they might be more accustomed to having a disease diagnosed and treated. This may lead to resistance to the use of medications based on such a risk. Similarly, medication compliance can become a limiting factor while targeting a large segment of a population with use of multiple medications on a daily basis. A new approach of polypill, a single pill containing a combination of multiple drugs either at full or half the normal can potentially address this limitation.18,28 It is proposed that a polypill can be given to a large segment of at risk population such as those above a specified age (e.g. 55 years) to increase medication compliance and reduce CVD risk.28
Population-based strategy
The second preventive strategy is the one where mass (population-based) approaches are used to target entire population to reduce cardiovascular risk. It is argued that even a small but population-wide reduction in the level of risk factor results in large overall beneficial effects.27 It needs health systems approach with a mass mobilisation, policy and legislative changes. Despite limited hard evidence to support such approaches, given the limitation of individual-based lifestyle change strategy, there is increasing interest in population-based strategies for cardiovascular risk reduction. A successful example of mass health promotion strategy in a developing country is from Mauritius, where an intervention involving use of mass media, legislative measures as well as health education in community, school and workplace was used to promote healthy nutrition, increase exercise, smoking cessation and reduction in alcohol intake20. The prevalence of hypertension, tobacco smoking and heavy alcohol consumption reduced, moderate physical activity increased and serum cholesterol levels were reduced.19 Lack of physical activity is emerging as an important cardiovascular risk factor in developing countries. Active travel such as walking, bicycling and using public transport has been suggested as a strategy to increase physical activity. In a cross-sectional study of a cohort in India, those bicycling to work were 50% less likely to have hypertension and 35% less likely to have diabetes indicating that promoting active travel in communities could potentially help in reducing cardiovascular risk.43 Reducing salt intake in the community is another strategy which is thought to reduce the risk of CVDs44 and the World Health Organisation recommends restricting daily salt intake to less than 5 grams per day.45 However, a large population in developing countries lives in rural areas where the climate is hot and loss of sodium through sweating may be high. Therefore, such recommendations for developing countries need to be backed by evidence from these countries. Tobacco control is another important way to reduce the risk of CVD. Uruguay instituted a series of comprehensive anti-smoking policies resulting in substantial reduction in tobacco use from 2005 to 2011.23 Other suggestions for mass approaches include use of technology. With increasing access to digital information in developing countries, such a strategy may be used to give health messages, provide information about primary and secondary prevention and sources of healthcare for treatment and prevention of stroke in developing countries. Innovative examples of such an approach include Stroke Riskometer a mobile phone based tool46 and use of soap operas47. The Government of India is planning to reach out to billions of people through its “Digital India” 48 campaign and such a platform can be potentially used to provide information about stroke prevention.
Current efforts towards prevention of stroke
Several developing countries are taking steps to reduce the risk of stroke. The Chinese Center for Disease Control and Prevention has drafted a China National Plan for Non-Communicable Diseases (NCD) Prevention and Treatment to increase awareness about non-communicable diseases, increase hypertension and diabetes control, reduce smoking and salt consumption and improve disease surveillance.49 Similarly, a large scale programme called the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) was launched by the Government of India in 2010 for early diagnosis and treatment of these diseases, promoting lifestyle modification and capacity building at various levels including training of manpower.22 Also, several developing countries in Latin America and the Caribbean have implemented national non-communicable diseases programmes and have taken policy measures to reduce tobacco and alcohol use, increase physical activities and encourage healthy dietary practices.21 More such commitments from governments of developing countries will be needed. At the same time the impact of national programmes for cardiovascular disease prevention on stroke mortality will need to be monitored so that corrective measures could be taken in time. The Sustainable Development Goals (SDGs) adopted in a United Nations General Assembly in 2015 calls for one third reduction in premature mortality due to non-communicable diseases by 2030 and this should provide impetus to developing countries to remove the barriers to cardiovascular diseases prevention.50
The way forward
The available evidence favours use of strategies for primary and secondary prevention in developing countries to reduce the risk of stroke. While lessons learned from developed countries would be important, developing countries would have to develop their own systems which work in the local context. In terms of achieving quick results, control of hypertension remains the most proven strategy. Lifestyle change would take longer time to implement but will bring sustainable results. Both need to be implemented simultaneously in developing countries. Use of community health workers to promote hypertension control, cardiovascular risk assessment and polypills are interesting emerging concepts and more evidence regarding acceptability and effectiveness is needed in developing countries. Table 1 provides a list of risk factors identified in the INTERSTROKE study and various interventions that are used or being trialled in developing countries. Several initiatives can potentially help improve stroke prevention. These include 1) national programs within health ministries for non-communicable diseases20–22; 2) development of culturally appropriate awareness, risk factor screening and treatment interventions with community participation20; 3) effective school health programs to educate the newer generations about the cardiovascular risks and promote healthy lifestyle at an early age20; 4) emphasis on health promoting environments e.g. availability of parks and biking or walking tracks; 5) implementation of successful governmental actions such as tobacco control policies21,23, banning of advertisements of alcohol21, promoting healthy diet21 and sin taxes (e.g. sugar taxes); 6) effective delivery of primary health care to control hypertension and other risk factors for stroke21 preferably through Universal Health Coverage and inclusion of medicines for stroke prevention in essential drug lists21 to make care affordable and accessible; 7) development of evidence-based guidelines and promoting adherence to the guidelines among medical practitioners as well increasing awareness among people about stroke risk factors by professional medical societies; and 8) effective use of existing and emerging technologies e.g. making digital blood pressure monitors widely available to screen for hypertension, use of social media, tools such as Stroke Riskometer43 and wearable technology (e.g. pedometers) to promote lifestyle changes.
Addressing knowledge gaps and prioritization
Significant knowledge gap exists regarding effectiveness of various stroke prevention strategies in developing counties. For example, it is unknown as to which interventions would be acceptable and cost–effective to reduce strokes in developing countries. Therefore, more research is urgently needed in this area. One of the major limitations for making policy and planning decisions, allocate resources and track the progress of stroke prevention in developing countries is the lack of good quality data on stroke epidemiology. Therefore, stroke surveillance needs to be significantly improved to generate high quality data on stroke mortality, incidence and prevalence. A recent nation-wide population-based study to estimate incidence, prevalence and mortality in China10 and a study in India to monitor trends in stroke mortality using verbal autopsies51 are good examples of attempts to improve stroke surveillance in developing countries. Efforts through the Global Burden of Disease Study have also helped to identify countries with high stroke burden. Several countries in Africa (e.g. Madagascar, Ghana, Liberia, Ivory Coast, Gabon, Republic of Congo), Asia (e.g. Russia, Kazakhstan, Afghanistan, Kyrgyzstan, Bangladesh, Myanmar, Vietnam, Cambodia, Indonesia, Philippines), South America (e.g. Guyana and Surinam) have higher DALYs lost due to stroke.52 Strengthening local health systems and providing Developmental Assistance for Health (DAH), can help reduce the burden of stroke expeditiously in many of these countries.
Role of the developed world
The developed world needs to be part of these efforts. Global clinical trials of stroke prevention will need to include more subjects from the developing world for results to be generalisable. Additionally, the genetic, ethnic and cultural diversity of the developing world can provide explanations regarding stroke pathogenesis that have not been found from studies on stroke in the largely Caucasian populations. For example, studies on secondary prevention strategies for stroke subtypes more prevalent in developing countries like intracranial atherosclerosis would be more feasible in these countries.53 Also, developed countries can help build local capacity to improve research and surveillance of stroke in developing countries. Working together to prevent strokes in developing countries can help both the developing and developed countries.
Sources of Funding
Dr Kalkonde is a Wellcome Trust/DBT India Alliance Fellow in Public Health.
Footnotes
Disclosures
None
References
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