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Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

10

Stroke

DEFINITION

A stroke occurs when blood vessels in the brain rupture or become occluded. Deficits resulting from stroke are usually maximal at onset (rather than steadily worsening, like the symptoms of a brain tumor), last more than 24 hours, and coincide with injury to the brain's vasculature as demonstrated by neurological and neuroimagining examination. Typical symptoms include muscular weakness, loss of sensation, problems with vision, and impaired speech. Depending on the location and severity of neuronal damage, additional symptoms, including loss of consciousness, may occur.

There are two main types of stroke: hemorrhagic and thrombotic (also known as ischemic). A hemorrhagic stroke may be caused by a ruptured cerebral blood vessel, a ruptured intracranial aneurysm, or an arterio-venous malformation leading to an intracerebral hemorrhage in or near the brain. (In this report, we do not address hemorrhage from arterial aneurysms and arterio-venous malformations, as their epidemiology differs significantly from that of other types of stroke). A thrombotic stroke results from the occlusion of one or more cerebral blood vessels. A thrombus may form directly on a diseased small vessel, or a large-vessel atherosclerotic plaque may embolize and block a smaller cerebral artery.[1]

A temporary interruption of the blood supply to a region of the brain, called a transient ischemic attack (TIA), usually results from narrowing of the carotid arteries due to plaque accumulation (carotid stenosis). Patients with TIAs experience a sudden onset of stroke symptoms and a focal loss of brain function lasting less than 24 hours. Studies from the United States and Europe indicate that within 2 to 5 years of their first TIA, between 8 and 33 percent of patients go on to have a full stroke.[2]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

SCOPE OF THE PROBLEM

Mortality

Stroke is a leading cause of disability and mortality throughout the world.[3,4] According to the World Health Organization (WHO), stroke kills approximately 4.6 million people (9 percent of all deaths) each year, and ranks as the second most common cause of mortality worldwide. The 1996 Global Burden of Disease study revealed that cardiac and cerebral vascular diseases have surpassed infectious and parasitic diseases to become the leading causes of death in the developing world, India and sub-Saharan Africa excepted.[ 5] In the People's Republic of China (PRC) alone, more than 1 million people die from stroke each year—three times the number of those who die from ischemic heart disease in that country.[6]

Among men and women aged 30–69, cardiac and cerebral vascular diseases cause three times as many deaths worldwide as infectious and parasitic diseases.[3] This age group generally comprises the most economically productive members of the workforce, a situation that serves to amplify the toll of death and disability associated with stroke and related disorders.[ 2,7] In South Africa, for example, stroke accounts for between 8 and 10 percent of all reported deaths and 7.5 percent of deaths among people of prime working age, 25 to 64 years old.[8]

Table 10-1 lists several additional reports describing stroke mortality in diverse populations. While the wide range of mortality rates shown may to some extent reflect population differences in exposure to risk factors for stroke (as discussed further below), the variation probably results as well from methodological differences among studies.[ 9] For example, in sub-Saharan Africa, most data on stroke mortality have been hospital-based, although the majority of stroke deaths in that region are thought to occur at home.[10] Box 10-1 describes an attempt to take this situation into account and produce more accurate measures of stroke mortality in urban and rural Tanzania.

Some studies in developing countries have found significant geographic [11] and ethnic [12,13] variations in stroke mortality within the same nation.[14,15] Other researchers, however, point out that such results need to be interpreted with caution as no standards exist for classifying ethnic groups.[16] Comparative data for more than 30 countries from 1950 to 1990 show increasing mortality from stroke in Eastern Europe, contrasting with declines seen in the United States; Europe; and Argentina, Chile, Uruguay, and Venezuela.[17]

Social and Economic Costs

In addition to causing early death, stroke results in significant nonfatal illness and disability. In the 1996 Global Burden of Disease study, stroke ranked as the sixth leading cause of lost years of healthy life and was responsible for about 2.4 percent of disability-adjusted life years (DALYs) worldwide.[5] Projections for 2020 place cerebrovascular disease—a more general term that describes any abnormality

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

BOX 10-1 Stroke Mortality in Urban and Rural Tanzania

Measuring stroke mortality in sub-Saharan Africa presents numerous problems. General mortality rates in this region are not well known because of the lack of reliable death certification systems, and few data are available on cerebrovascular disease or its risk factors. Community-based research in developed countries indicates that many people die of a first stroke before reaching a hospital, a scenario that appears even likelier to occur in Africa. A recent study by Walker and co-workers attempted to circumvent these problems through the use of key informants and so-called verbal autopsies in three contrasting regions of Tanzania, with a total population of more than 300,000. The three surveillance areas were urban Dar-es-Salaam; Hai district, a relatively prosperous rural area; and Morogoro district, an impoverished rural area.

Over a 3-year period, key informants provided mortality information for an annual or semiannual census. For each reported death, clinical officers identified the cause through the use of a standard questionnaire presented to family members of the deceased; the results were coded by physicians and further validated through a variety of measures. The study determined age-specific stroke mortality rates for men and women in the three areas, compared with 1993 rates for England and Wales. Stroke mortality rates for each of the Tanzanian communities were higher than rates in England and Wales for all age bands up to 65 years. The total number of adults dying from stroke in Tanzania is low in comparison with similar figures from other developing countries, however, since only about 6 percent of the Tanzanian population is older than 65. it appears likely that as increasing numbers of people in sub-Saharan Africa survive to old age, there will be a significant increase in mortality due to stroke.

Source: [10]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

TABLE 10-1 Stroke Mortality: Selected Studies

Country

Population

Method

Rates (per 100,000)

China (PRC) [18]

Urban and rural (29 provinces, 5,800,000)

Door-to-door survey with follow-up neurological examination

77 (crude)

81 (age-adjusted)

China (PRC) [6]

Rural (Inner Mongolia)

Door-to-door survey with follow-up neurological examination

45 (age-standardized)

China (PRC) [6]

Rural (Tibet)

Door-to-door survey with follow-up neurological examination

370 (age-standardized)

Mexico [19]

Urban and rural; multiple sites in Mexico

Population-based; epid emiological surveillance data from hospital records and surveys

25 (crude)

Philippines [20]

Urban and rural

Vital statistics records from ministry of health, 1963-76

32

Singapore [21]

Urban and rural

Population-based; annual death registries, 1970–1994

50–60 (crude)

59 (age-standardized)

South Africa [22]

Rural; 35 years and older (932 deaths)

Community-based study; census, death records, and verbal auto psies

127 (over 35 years) 80 (35 to 64 years) 338 (over 64 years)

Tanzania [10]

Three regions (urban poor and prosperous rural); 307,820 popul ation (181,888 aged 15 or older)

Death and hospital records confirmed with verbal autopsies

95–420 for men, 55–317 for women (age-adjusted; 15 years and older); 35–65 for men, 27–88 for women (age-adjusted; 15–64 years)

Venezuela [23]

All ages

Ministry of health records

30

Vietnam [24]

Three regions (Ho Chi Minh City and two rural areas) with a total population of 52, 649

Door-to-Door survey with follow up examination

131 (age-adjusted)

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

of the brain resulting from blood vessel pathologies—fifth among the causes of disease burden as measured in DALYs for developing countries, and fourth worldwide.[25]

The extensive and intensive care frequently required by stroke victims places disproportionate demands on limited resources for health care in many developing countries.[26] For example, in one Zambian bush hospital during a 6-month period, stroke patients comprised less than 5 percent of total admissions but consumed 14 percent of all intensive care unit bed days.[27]

When a person dies or becomes disabled as a result of stroke, the negative repercussions of that event extend beyond the victim's family to the community, the nation, and the global economy. The death of an adult family member can have a devastating impact on the household. Caring for a family member disabled by stroke can harm the caregiver 's own health, productivity, and ability to earn money.[28] The resulting losses in production, earnings, investment, and consumption affect local, regional, national, and global economies. Among many developed-country populations, 0.2 percent suffer a stroke each year. Of those afflicted, one-third remain permanently disabled, and one-third make a reasonable recovery. The two-thirds who do not die form a large pool (about 1 percent of the population) of stroke survivors, of whom at least half are disabled, making stroke the most important single cause of severe disability among people living in their homes.[ 29] Unfortunately, such studies have not attempted to assess or document the social and economic costs of stroke in developing countries, where more than two-thirds of all strokes are thought to occur.[ 9]

The social and economic costs of stroke in developing countries are expected to persist—and probably increase—over the next two decades.[30] The following factors are most frequently cited to explain this trend [31]:

  • Reductions in infant and childhood mortality, allowing greater proportions of people in developing countries to survive beyond age 64, when 75 percent of all strokes occur.[2,9,30]

  • The growing adoption of behaviors and lifestyles known to elevate stroke risk, such as tobacco use and high saturated fat intake, that can lead to hypertension, obesity, and diabetes (see the discussion of risk factors below). For example, current predictions indicate that by 2020, 12 percent of all deaths and 9 percent of all DALYs will be attributable to tobacco alone; the vast majority of this increased burden is projected to arise in developing countries.[ 32,33]

  • Although evidence from industrialized countries demonstrates that stroke and other vascular disorders can be significantly reduced through interventions at the individual, community, and national levels, this knowledge and experience have yet to be applied systematically among the populations of developing countries.[34,35]

  • There is a lack of awareness of cost-effective options for reducing the impact of stroke, as well as concern in some quarters that such investments may

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

detract from efforts to control communicable diseases and to promote maternal, child, and reproductive health.[30]

Along with the above factors, which influenced the rise of stroke and other cardiovascular and cerebrovascular diseases in developed countries and are now becoming prominent in the developing world, there appear to be additional factors specific to developing populations that could exacerbate the pending epidemic of these diseases. For example, researchers have documented relatively high rates of obesity, hypertension, glucose intolerance, and ischemic heart disease—all risk factors for stroke—among adults whose growth was stunted during childhood. Among populations where food has been historically scarce, “thrifty genes” appear to predispose bearers to obesity and diabetes when food is plentiful.[30]

The seriousness of the threat posed by cerebro- and cardiovascular disease must be clearly demonstrated to the governments of developing countries. Stroke deserves particular attention as a preventable and treatable illness with profound medical, economic, and social consequences. Confronting the epidemic of stroke that threatens developing countries will require a better understanding of the origins of the disease, prediction of its magnitude, and timely implementation of preventive and case-management strategies.[30]

PREVALENCE AND INCIDENCE

Prevalence and incidence rates for stroke vary dramatically from one population to another. The reasons for this heterogeneity are not completely understood and are currently being explored in several large-scale epidemiological studies. Three broad sets of factors have been proposed as likely explanations for differences in the prevalence and incidence of stroke [2]:

  • The stage of economic development, which appears to play a role not only in the prevalence and incidence figures for a given geographic region, but also in the specific type of stroke present.

  • Differences in behavior and lifestyle that expose populations to varying types and degrees of risk factors, such as smoking, physical inactivity, obesity, ethanol use and abuse, and high sodium and saturated fat intake.

  • Differences in hereditary predisposition to cerebral and cardiovascular diseases. Although the results of research to determine specific genetic risk factors for stroke have been inconclusive, epidemiological data suggest the existence of significant differences in the cause, type, and prevalence of stroke among different ethnic populations.[ 36] Genetic studies in diverse populations could provide a new perspective on the basic pathogenic mechanisms underlying the vascular disease process.

Developing countries have recently begun to join the developed world in experiencing the so-called epidemiological transition of diseases. Control of infectious and parasitic diseases, along with improvements in nutrition, have

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

lengthened the average life span in many parts of the world. As a result, the spectrum of disease is shifting away from communicable diseases and perinatal and nutritional disorders to predominantly noncommunicable diseases, most notably cardiovascular disease.[37,38] Early in the epidemiological transition, most strokes tend to be hemorrhagic. Hypertension is an important risk factor for this type of stroke, which often occurs in people with low blood cholesterol levels. As the transition progresses, thrombotic strokes account for an increasing fraction of mortality, and ultimately become the most prevalent stroke type.[2]

During the 1980s, WHO undertook a major international effort to monitor stroke prevalence and incidence in 10 countries of Asia and Europe: the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project.[3,39] Unfortunately, neither Latin American nor African countries were studied. Despite this limitation, the MONICA Project, through the use of uniform and statistically valid procedures, provided comparisons across populations in areas as different as Novosibirsk in the Russian Federation and Fruili in Italy. In the ideal, community-based settings in which MONICA was conducted, over-all stroke occurrence and mortality rates were found to be twice as high among men than women, and higher in Finland, Lithuania, the Russian Federation, and the PRC than in western and central Europe.

MONICA populations were defined as all residents of the study areas according to geographic and administrative boundaries. Stroke events were identified through standard protocols, and cases were coded according to the International Classification of Diseases (ICD). Death certificates provided the major source of data on stroke mortality; hospitalized cases were identified from admission lists, discharge diagnoses, and other available medical record information. While considerable effort was made to ensure the quality of the data, researchers have noted some discrepancies, as well as a general need to interpret multinational comparisons of stroke statistics with caution.[4]

Prevalence

Table 10-2 shows the broad range of stroke prevalence reported in studies conducted throughout the developing and developed worlds. Similar variation in stroke prevalence has also been reported within single countries. In India, for example, neuroepidemiological data on stroke collected over the past 30 years have revealed prevalence rates as low as 44 in rural areas and as high as 842 per 100,000, among the urban Parsi community in Bombay.[40] Studies conducted across many regions of India indicate that stroke accounts for 2 percent of hospital registrations, 1.5 percent of medical registrations, and 9 to 30 percent of neurological admissions.[ 41,42,43 and 44]

Reliable studies of stroke prevalence would be particularly valuable in estimating the impact of the disease since, as noted above, many stroke patients survive with some disability for many years. However, most studies on stroke prevalence in developing countries have been based on hospital records, and thus describe only those patients —a minorityin many low-income communi-

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

ties—who received hospital treament. Community-based research, while difficult to perform in developing countries, represents the best means of obtaining accurate estimates of stroke prevalence—information that could be used not only for health care planning, but also for clues to risk factors, preventive strategies, and treatments.[22,45] Two examples of the few existing studies of this type were conducted in the Hai district of Northern Tanzania [22] and the island of Kinmen in the Republic of China (Taiwan).[45] Although the focus of each study was quite different, both employed door-to-door surveys, followed by neurological examination to confirm diagnoses.

Incidence

As is the case with studies of stroke mortality and prevalence, reports of stroke incidence rates indicate wide variation throughout the developing world (see Table 10-3). Rates of 200 per 100,000 or higher have been reported in several Asian countries [6,24,26] and in Russia,[47] while stroke appears to be nonexistant in Kitava, New Guinea.[48] Researchers have offered a variety of explanations for low stroke incidence, including young populations, lack of influence of Western diets, low diastolic blood pressure, and low cholesterol levels.[ 49,50] A substantial decrease in stroke mortality noted over recent years in the United States remains unexplained, but appears to be due to individual lifestyle modifications, as well as improvements in the general environment and in medical care.[51]

Several studies have revealed high rates of stroke incidence among young people in low-income countries as compared with the developed world. In India, for example, an analysis of the Stroke Registry established at NIMHANS showed that 20 percent of strokes occurred in people younger than age 40. Stroke among children, while comparatively rare relative to adults, may prove more common among developing populations prone to sickle cell anemia, an apparent risk factor for stroke,[ 52] as well as other conditions discussed below.

Incidence studies have also revealed variation in the occurrence of the two types of stroke among different populations in the developing world. In several West African countries, approximately two-thirds of all stroke cases are ischemic, and one-third are hemorrhagic.[ 53,54,55 and 56] In Iran, two-thirds of strokes were found to be ischemic in origin.[ 57] In the PRC, hemorrhagic stroke is as common as ischemic. Consistently, 30 percent of stroke cases are hemorrhagic in Singapore, Malaysia, Thailand, Indonesia, Hong Kong, the Philippines, Taiwan, and South Korea.[58,59]

Comparing stroke incidence in different countries and observing incidence trends in specific populations may increase our understanding of the disease. However, such comparisons cannot be made until studies of stroke incidence use the same definitions, methods, and mode of data presentation. While MONICA and other recent studies have begun to address this problem in some parts of the world, the profound lack of comparable incidence data for Africa, Asia, and South America largely excludes the developing world from such analyses.[60,61]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

TABLE 10-2 Stroke Prevelance: Selected Studies

Country

Population

Method

Rate (per 100,000)

China (PRC) [18]

Urban and rural sites (5,800,000)

Door-to-door survey with follow-up neurological examination

260 (age-adjusted) 246 (crude)

Colombia [62]

Urban (13,588)

Door-to-door survey

559

Ecuador [63]

Rural (1,113)

Door-to-door survey; questionnaire; neurological screening examina tion

360

Ethiopia [64]

Rural (60,820)

Door-to-door survey

15 (disability due to stroke only)

India [40]

Urban; Parsis living in Bombay (14,010)

Detailed neuroepidemiological study

842

India [65]

Rural; Kashmir

House-to-house census

143

Nigeria [66]

Rural (18,594)

Questionnaire; examination

58

Peru [67]

Rural (3,246)

Door-to-door survey

647

Saudi Arabia [68]

Hospital-based (500)

Review of records; diagn osis confirmed by computed tomography

186

Taiwan (ROC) [45]

3,915 residents of the islet of Kinmen, age 50 and over

Door-to door interview; neurological examination of all partici pants

2,450 (lifetime prevalence

Tanzania [10]

Rural; Hai District 148,135 (82,152 age 15 and over)

House-to-house census, interview, examina tion

73 (127 age 15 and over)

Tunisia [69]

Urban (34,874)

Community-based survey; follow-up control survey

140

Vietnam [24]

Three regions (Ho Chi Minh City and two rural areas) with a total population of 52, 649

Door-to-door survey with follow-up neurological examination

608 (age-adjusted)

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

TABLE 10-3 Stroke Incidence: Selected Studies

Country

Population

Method

Rate (per 100,000)

China (PRC) [18]

5,800,000

Door-to-door survey with follow-up neurological examination

116 (standardized to world populations) 110 (crude)

Singapore [70]

Urban and rural (5,920)

Cohort study examining three previous cross-sectional surveys and longitudinal follow-up from national registry data

Chinese: 230 (male); 120 (female)

Malay: 160 (male); 280 (female)

Indian: 220 (male); 150 (female)

Iran [57]

   

44 (men)

59 (women)

Kuwait [49]

Urban

Hospital and primary care clinic registries with clinical evaluation

28 (crude)

145 (age-adjusted)

Libya [71]

Benghazi (52,000)

 

63

Nigeria [72]

Urban (Ibadan)

Hospital-based; stroke registry

74.8 (standardized to world population)

Papua New Guinea [50]

Kitava Island; traditional horticulturalists uninfluenced by Western diets (220)

Cardiovascular and neurological screening examinations

0

Russia [73]

Novosibirsk (150,000)

Population-based; stroke registry

232

Saudi Arabia [74]

545,000

Stroke registry (1989–93)

30 (crude); 126 (standardized to 1976 U.S. population)

Taiwan (ROC) [75]

3,915 residents of the islet of Kinmen, age 50 and over

Door-to door interview; neurological examination of all partici pants

527

Tunisia [76]

Tunis

Stroke registry

192 (age-adjusted, 45 years and older)

Vietnam [24]

Three regions (Ho Chi Minh City and two rural areas) with a total population of 52,649

Door-to-door survey with follow-up neurological examination

250 (age-adjusted)

Zimbabwe [77]

Urban (black residents of Harare; total population 887,768)

Prospective community-based

68 (standardized to world population); 30.7 (crude)

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

Recommendation 10-1. Data collection should be improved to provide accurate information about stroke mortality, morbidity, incidence, prevalence, and mechanisms in developing countries using culturally sensitive tools and diagnostic techniques. Pathological studies of stroke should be conducted to determine the relative prevalence of various stroke subtypes among several diverse representative populations in developing countries. This research would be greatly enhanced if conducted in collaboration with research centers in high-income countries utilizing other existing data and research mechanisms.

RISK FACTORS

The term “risk factor” was coined by investigators in the Framingham Heart Study, one of the largest, longest-running, and best-known epidemiological studies of its kind. Considerable data on risk factors for stroke have come from the 850 participants who have experienced a stroke since the U.S. study began in 1950.[78] While several of the predominant modifiable risk factors for stroke identified in the Framingham study—most notably hypertension, diabetes, and smoking—appear generalizable to many populations, data documenting the relative impact of these factors in developing countries are sparse. This represents fertile ground for future epidemiological studies, as does the possibility that new stroke risk factors of particular significance in developing countries might be identified (for example, infectious agents, nutritional factors, or developmental syndromes that rarely occur in developed countries).[30] At present, the risk factors described in this section represent the most promising targets for preventing and treating stroke in the developing world. Additional factors associated with stroke outcome are subsequently discussed.

Physiological
Hypertension

The foremost risk factor for stroke throughout the industrialized world, hypertension may play an even greater role in causing stroke in low-income communities. Epidemiological studies among populations of East Asia, including the PRC [79] and Africa [80,81], indicate that controlling elevated blood pressure in these populations could prevent proportionately more strokes than equivalent measures in Western populations.[44] The reasons for the apparently stronger influence of hypertension on strokes among East Asian and black African populations remain to be identified, but may include both genetic and environmental effects, as well as longer exposure to untreated conditions of hypertension. Both populations were found to suffer a far higher proportion of hemorrhagic strokes as compared with Western populations.

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

Hypertension increased the risk of stroke threefold among both men and women in every age group monitored in the Framingham study.[ 82] A statistical overview of prospective epidemiological studies of middle-aged individuals with no previous history of vascular disease, examining the relationship between diastolic blood pressure and stroke, showed a doubling of the risk of stroke for every 7.5 (mm Hg) rise in blood pressure.[83] Similarly, among East Asians, projections indicate that a population-wide reduction in diastolic blood pressure of 3mm Hg would reduce stroke mortality by one-third.[79] In the PRC, carefully conducted epidemiological studies revealed a north–south gradient in stroke mortality and incidence that was shown to be due mainly to differences in the prevalence of hypertension, which was higher in the northern provinces.[6] The highest prevalence of hypertension was 22.3 percent in the province of Tibet, and the lowest was 4.8 percent in the province of Qinghai. A 10 percent higher prevalence of hypertension was associated with a 2.8-fold higher incidence of stroke, even after adjustment for differences in prevalence of cigarette smoking and alcohol consumption.[ 6,46]

Hypertension is a major public health problem in African countries, where it may affect up to 10 percent of the population and contributes to coronary heart disease, as well as to hemorrhagic and thrombotic stroke. Studies from Nigeria, Ivory Coast, and Zimbabwe found hypertension to be the main risk factor for both ischemic and hemorrhagic stroke.[ 22,72,77] The condition frequently goes unrecognized, however, in part because many African health care providers lack reliable equipment for measuring blood pressure.[27]

The results of controlled clinical trials of treatments for hypertension in developed populations may inform research in the developing world. Clinical studies in developed populations indicate that blood pressures of less than 140/83 mm Hg are optimal for stroke prevention. Therefore, the goal of antihypertensive therapy should be to normalize rather than just reduce blood pressure.[84] Additionally, recent studies and resulting data from both developed and developing countries indicate that high systolic blood pressure is equally or more important, especially in older adults (over age 65), as a predictor for stroke.[85,86,87,88,89 and 90] Antihypertensive therapy for systolic hypertension will be important for reducing the risk of stroke in elderly populations. Antihypertensive therapy has been found to reduce the risk of stroke by about 42 percent in people younger than age 65 suffering from high blood pressure.[ 88] Unfortunately, studies of patients who received antihypertenstion medication through urban clinics in both South Africa [89] and Saudi Arabia [91] indicate that many patients who receive the medication use it incorrectly, and few recognize that uncontrolled hypertension can lead to stroke.

Diabetes

Several studies in developed countries—notably the Framingham study [82] and the Honolulu Heart Study [92]—have documented diabetes as a risk factor for stroke. The Framingham study found a 10 percent increase in risk for having a

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

stroke among males with diabetes; this proportion rose to over 20 percent when the patient was also hypertensive.[82] In Africa, studies from Senegal, Ivory Coast, Tunisia, and Nigeria link diabetes mellitus with stroke in 2-27 percent of cases.[56,72,93] A community-based study in rural and urban areas of Tanzania revealed that stroke accounted for approximately one-third of all deaths among those with diabetes. The researchers also discovered that, although the prevalence of diabetes in Tanzania was low in comparison with developed countries, mortality rates attributed to diabetes were on a par with those in the United States.[94] This result suggests that untreated diabetes, like untreated hypertension, represents a major contributor to stroke mortality in the developing world. Moreover, the number of adults with diabetes is projected to rise from 135 million in 1995 to 300 million in 2025, with 75 percent of those affected being expected to reside in developing countries.[2] If this increased prevalence of diabetes is not met with a comcomitant increase in access to medication, many of those affected will be at significantly increased risk for stroke.

Cardiac Disease

Cardiac disease has been shown to be a major predisposing factor for stroke among elderly people in developed countries, and is expected to rise in prominence in developing countries as increasing numbers of people reach old age. Most participants in the Framingham study who suffered stroke were found to have such comorbid conditions as congestive heart failure, coronary artery disease, or atrial fibrillation; the last condition appeared most significant among elderly populations, where it was found to account for approximately 30 percent of all strokes.[95]

In developing countries, cardiac diseases are also recognized risk factors for stroke; however, there are variations in the type of cardiac disease and the affected age groups.[96] Though not common in developed countries, rheumatic heart disease (and causal rheumatic fever) is especially predominant in sub-Saharan Africa and rural India, affecting mainly those aged 5-15. Rheumatic heart disease is frequently a risk factor for stroke in both children and adults who suffer the chronic and deteriorating affects of that disease.[97,98,99 and 100] A recent study of hospitalized black South African stroke patients (mean age 55 for men, 60 for women) found coronary artery disease to be much more prevalent than had previously been reported in similar groups, as well as in the general nonstroke black population. Such patients, the researchers concluded, may have a risk for coronary artery disease similar to that of white South Africans.[101] The difference in findings between this South African study and other studies conducted in Africa may be explained by two factors: (1) a lack of accurate data due to the absence of adequate data collection tools and proper diagnosis, and (2) increasing rates of coronary artery disease due to the demographic transition occurring in many African countries.[102,103] The prevalence of coronary artery disease in India and China continues to increase.[104,105,106, and 107]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×
Elevated Serum Cholesterol

Although elevated serum cholesterol is a well-documented risk factor for ischemic heart disease, which in turn is a risk factor for thrombotic stroke, several studies in developed countries have failed to demonstrate a relationship between cholesterol levels and stroke risk. The Honolulu Heart Study indicated that elevated serum cholesterol predicts a higher stroke rate when stroke is assessed 15 years after the cholesterol measurement.[108] Interestingly, clinical studies indicate that statins, cholesterol-lowering agents, reduce stroke risk by 30 percent, although this result may be due to other effects of these drugs, such as reduction of smooth muscle proliferation, reduction of inflammation, and restoration of impaired endothelial function.[109,110]

Few researchers have examined the relationship between stroke and serum cholesterol in developing countries. Among East Asians, elevated cholesterol appears to be a far less potent risk factor for stroke than hypertension. In these populations, elevated serum cholesterol appears to influence primarily stroke type, rather than occurrence.[ 79] Such a relationship might also be expected to occur in populations that experience relatively high rates of hemorrhagic stroke.

Elevated Serum Homocysteine

A recent study found that elevated serum homocysteine (15.4 mmol/liter or more) is associated with a fourfold increase in stroke risk among men.[111] Several recent studies indicate that elevated serum homocysteine is a risk factor for stroke in both adults and children.[112,113,114 and 115] Studies indicate that a deficiency of B-complex vitamins is attributable to elevated serum homocysteine.[111,116,117,118 and 119] How chronic, low-grade, or severe malnutrition and/or hypovitaminosis relate to the homocysteine/stroke issue is not known presently, but has significant implications for both children and adults in developing countries. Findings on this relationship would indicate the potential for preventing stroke by treatment with vitamins B6, B12, and folic acid.[111,120,121] More data are needed from developing countries to establish the likely causal relationships among vitamin deficiency, elevated levels of serum homocysteine, and the occurrence of stroke in these settings.

HIV/AIDS

Several clinical and autopsy studies have suggested an increase in stroke among those with HIV/AIDS. These studies, however, were conducted in populations with confounding factors, such as drug abuse and coexistent opportunistic infection.[122,123,124,125 and 126] A retrospective case-controlled study of young (below age 50) black African stroke patients in the KwaZulu Natal Province of South Africa found a higher rate of large-vessel stroke in patients who had HIV.[ 127] A recent study in Thailand has also shown stroke in children to be an indicator of undiagnosed HIV infection.[128]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Postpartum Cerebral Venous Thrombosis

Studies in both developed and developing countries indicate that postpartum cerebral venous thrombosis (CVT) is a risk factor for stroke.[129,130,131 and 132] In developed countries, postpartum (or puerperium) CVT accounts for 5 to 20 percent of all cases of CVT, but the figure in developing countries is estimated to be as high as 60 percent.[131,132 and 133] In developing countries, several risk factors, including low nutritional status, anemia, and dehydration resulting from the cultural practice of restraining fluids during the first days after delivery, are thought to account for this trend.[43,133] Postpartum CVT occurs frequently among the poorest Indian women; nearly 30 percent of those affected die from the disorder.[43,134] The administration of properly dosed anticoagulants immediately following the occurrence of CVT-induced stroke can reduce mortality to less than 20 percent and often reverses most of the initial disabling conditions (motor, vision, speech impairment).[129,130]

Risk Factors for Stroke in Children

As noted earlier, stroke in children is uncommon worldwide, but may occur at higher levels in some developing communities as a result of the presence of several known and suspected risk factors, including sickle cell disease, congenital heart disease, intracranial infections, and metabolic disorders.[43,52,135,136 and 137] Nearly one-third of the strokes suffered by a group of 35 Cameroonian children between 5 months and 15 years of age were attributable to sickle-cell disease; other identified risk factors included heart disease, cerebral malaria, and meningitis.[138]

Behavioral
Cigarette Smoking

Findings on the effect of cigarette smoking as a contributor to stroke have been variable in some populations. However, many studies have found an association between cigarette smoking and stroke risk, either directly or through smoking-related increases in blood pressure.[ 139,140,141,142 and 143] In the Framingham study, heavy smokers (> 40 cigarettes/day) were found to have a relatively high risk of stroke—twice that of light smokers (< 10 cigarettes/day). Participants (both men and women of all ages) who quit smoking, however, appeared to revert to risk levels near those of nonsmokers within 2 to 4 years.[141]

Cigarette smoking may prove an especially important risk factor for stroke in developing countries,[142] where nearly three-quarters of the more than 1 billion people who use tobacco regularly currently reside.[143] Moreover, the annual tobacco-related death toll in developing countries is predicted to triple by 2030, resulting in a yearly loss of 10 billion lives.[34] Epidemiologists already estimate that the rate of smoking among blacks in South Africa, for example,

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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has doubled over the past 10 years, contributing to an increased risk of stroke in that population.[89]

Diet

Dietary change represents an important component of the epidemiological transition [30]. Increased consumption of foods high in saturated fat, cholesterol, and salt in developing populations is expected to produce concomitant increases in hypertension, obesity, and diabetes, all of which contribute to stroke risk.[144]

Alcohol Abuse

Alcohol has been reported to have a dose-dependent effect on the risk of hemorrhagic stroke.[145,146,147 and 148] Some studies have indicated that low to moderate levels of alcohol consumption may actually offer some protection against ischemic stroke, [147, 149] while others [150,151] have found no such benefit. A prospective study of Chinese men aged 45 to 64 found an association between the consumption of small amounts of alcohol and lower overall mortality, including death from ischemic heart disease, but no beneficial effect of alcohol on death due to stroke; a study of elderly Taiwanese reached a similar conclusion.[ 152,153] The differing results of these studies may be influenced by genetic predisposition among different ethnic groups, indicating a need for more research on the relationship between moderate alcohol consumption and risk for ischemic stroke.

Physical Inactivity

The evidence is not conclusive on the role played by exercise in preventing stroke. Previous studies have found either no or a positive effect of exercise.[154,155 and 156] In the Framingham study, physical activity was found to be negatively correlated with stroke risk among men. Studies have shown that those who maintained moderate or high levels of exercise had a lower stroke risk than those who were inactive.[157,158] Insofar as even moderate levels of exercise contribute to maintaining normal weight, controlling diabetes, and improving cardiovascular health, it can be surmised to serve as a preventive against other risk factors.[159,160]

The remarkable reduction in stroke mortality achieved in several Western countries since 1970 suggests that population-wide efforts to educate people about causes and risk factors for stroke and other cardio- and cerebrovascular diseases are effective in reducing the impact of these disorders.[51] The concept of stroke as a serious condition may be highlighted at the public level using terms such as “brain attack,” applied in the same context as heart attack. One such campaign was recently carried out in India (March 2000) as part of Brain

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Awareness Week. The campaign was conducted by neurologists and featured a special education program in neurosciences for public audiences, as well as high school and college students. Presentations given on stroke introduced the concept of brain attack to emphasize the significant risk posed by stroke to overall health and functioning.[ 161] Indian medical professionals and government officials, as well as those from other developing countries, have begun to recognize that the evidence on stroke clearly indicates an impending public health disaster. Therefore, as a first step toward blunting the effects of these trends, the committee makes the following recommendation.

Recommendation 10-2. Public education strategies to raise awareness of stroke and of environmental and behavioral risk factors for the disease should be designed and implemented in developing countries by national public health agencies and community-level health care services. These strategies should be accompanied by urgent primary health care initiatives (see Recommendations 10-8 and 10-9) focused on the early detection and treatment of hypertension, diabetes, and other known risk factors for stroke.

Although the available scientific evidence suggests that most of the risk factors for stroke identified for industrialized countries are also applicable to developing countries, the special genetic and environmental conditions prevalent in Africa, Asia, and Latin America call for specific case-control studies on risk factors for stroke among these populations. The scientific knowledge gained from these studies could be applicable to African-, Hispanic-, and Asian-American populations that at present are at higher risk of stroke morbidity and mortality in the United States.[95,162] The Countrywide Integrated Noncommunicable Diseases Intervention (CINDI) Program and Conjunto de Acciones para la Reduccion Multifactorial de las Enfermedades No Transmisibles (CARMEN) protocols could serve as a basis for conducting such studies in African, Asian, and Latin American countries.

Recommendation 10-3. Case-control studies should be designed and conducted to assess risk factors for stroke in Africa, Asia, and Latin America. To make the findings of this research widely available and inform efforts for ethnic populations worldwide, developing countries should become involved in existing international networks, such as the MONICA and CARMEN strategies sponsored by WHO and the Pan-American Health Organization (PAHO), respectively.

Factors Affecting Course and Outcome

Extensive studies of stroke outcome have been limited largely to the developed world, but may be somewhat generalizable to developing populations as well. Overall, these studies indicate that stroke outcome depends primarily on

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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the type of stroke and the presence of comorbid conditions.[36,113,145] Stroke outcomes are commonly described using the terminology of the National Institutes of Health (NIH) Stroke Scale.[163,164]

Stroke worsening occurs most frequently following large-vessel strokes. Early worsening must be distinguished from conditions such as cerebral edema, mass effect, hemorrhagic transformation, and metabolic disturbances.[ 164]

Stroke recurrence most frequently follows large-vessel and atherosclerotic strokes. The risk of recurrence has been found to be one to four percent in the first 30 days after a stroke, increasing to between 8 and 25 percent at 1 year (depending on stroke subtype and comorbidity), and climbing to 20 to 45 percent at 5 years.[165] Additional predictors of recurrence include elevated blood glucose, hypertension, age, coronary artery disease, atrial fibrillation, congestive heart failure, prior transient ischemic attacks, a low albumin/globulin ratio, and heavy alcohol consumption. Congestive heart failure also appears to be a strong predictor of stroke recurrence, and has been associated with about a 26 percent risk of recurrence at 3 years. Hyperglycemia is associated with about a 17 percent risk of 3-year recurrence.[164,165]

Functional disability is an approximate measure of a stroke's effect on a patient's daily activities. One simple scale, developed in France, classifies patients into four groups: Class 1, no sequelae, with the patient being able to return to previous work activities; Class 2, functional sequeleae, where the patient is autonomous but slightly impaired; Class 3, important sequelae, denoting severe impairment; and Class 4, bedridden.[166]

Quality of life reflects a combination of a patient's clinical status with social and psychological aspects of health. After a stroke, patients in developed countries are frequently unable to return to work, unwilling or unable to continue their rehabilitation once discharged from the hospital, and clinically depressed.[167] Many experience sexual dysfunction and stressful relationships and demonstrate abnormal social behavior.

Morbidity due to stroke is usually assessed as 30-day case fatality, which is greatest after intracerebral hemorrhage (48-82 percent) and lowest after ischemic infarct (8-15 percent). About 8 percent of patients experiencing ischemic strokes die within 30 days, about 21 percent within 1 year, 31 percent within 3 years, and 44 percent within 5 years. Approximately half of early deaths are attributable to the stroke itself, whereas recurrent stroke and cardiac disease have a greater impact on long-term mortality.[165] Large-volume strokes, decreased level of consciousness, and major basilar or hemispheric infarcts are associated with the highest case fatality, whereas patients with lacunar syndromes have the highest survival rates. Cardioembolic stroke is associated with about 15 percent of 30-day mortality, but with the worst long-term mortality.[ 166] Other predictors for long-term mortality due to stroke are age, cardiac disease, congestive heart failure, and elevated blood glucose.[ 167]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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INTERVENTIONS

Prevention

Because of the high risk for death, long-term disability, and recurrence after a first stroke, prevention is key to reducing the public health impacts of cerebrovascular disease. Moreover, the relatively high costs and limited benefits of treatment and rehabilitation for stroke underscore the importance of efforts to prevent the disease in areas where health care resources are limited. Prevention strategies can be divided into three categories from the perspective of risk factors: (1) primordial prevention is directed toward the prevention of risk factors themselves; (2) primary prevention focuses on reducing the impact of existing risk factors; and (3) secondary prevention is directed toward early detection and management of existing clinical diseases (e.g., hypertension, diabetes, heart disease, and stroke itself).[2]

Primordial prevention tends to focus on entire populations. At this level, stroke prevention is best undertaken through a broad preventive health program for vascular disease that promotes a healthy lifestyle encompassing diet, exercise, and the avoidance of smoking and excess alcohol consumption.[ 8] Targeted campaigns may be directed at general, modifiable risk factors for cardioand cerebrovascular disease, most notably smoking. Research indicates that community-wide education programs can result in a significant reduction in the prevalence of smoking and other cardiovascular risk factors and may be very cost-effective.[168] More specifically, in a randomized controlled trial, simple advice to give up smoking with a minimum of supportive counseling was found to reduce mortality from lung cancer and coronary heart disease, although the incidence of stroke was not analyzed separately.[169] Cost-effectiveness analyses demonstrate that tobacco-control campaigns cost US $20–70 per year of life saved.[2] Since smoking represents not only a significant modifiable risk factor for vascular disease, but also a growing drain on personal and public resources in developing countries, the committee makes the following recommendation.

Recommendation 10-4. Governments should develop, strengthen, and enforce legislation intended to reduce tobacco use. This could include tariffs or other programs designed to limit use of tobacco by raising its price, as well as legislation that protects nonsmokers from exposure to cigarette smoke in public places.

Primary prevention of stroke has been found effective in randomized trials in industrialized countries aimed at lowering stroke risk factors, such as high-fat, high-cholesterol, or high-sodium diets; hypertension; and cigarette smoking. As a first step toward undertaking similar efforts in developing countries, provisions must be made for the detection of conditions that represent risk factors for stroke at the level of primary care. This is particularly true of hypertension and diabetes, which frequently go undiagnosed in developing populations because of a lack of adequate medical services.[27]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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Recommendation 10-5. Primary care providers in developing countries should be provided with the training and equipment necessary to conduct preventive monitoring of conditions that are known risk factors for stroke, including hypertension, diabetes, and coronary artery disease.

Secondary strategies for stroke prevention include treatment for conditions that are known risk factors for stroke, such as hypertension, diabetes, coronary artery disease, and TIAs, as well as measures to prevent stroke recurrence. Case-management strategies have been investigated extensively among patients with stroke. Recent projections from epidemiological data in the United States suggest that adequate control of hypertension, warfarin treatment for atrial fibrillation cases, and cessation of smoking could prevent more than half of the estimated 731,000 strokes that occur in the U.S. each year.[170] Other strategies that have been successful in industrialized countries involve sophisticated and expensive technologies, such as thrombolytic therapies, automated internal defibrillation, and cardiac surgery, that are unlikely to become available in developing countries in the near term.

On the other hand, several low-cost treatments for hypertension and other conditions are likely to significantly reduce the incidence and severity of stroke and stroke-related vascular disease in developing countries. These include low-dose thiazide, aspirin, and beta blockers (and, where costs permit, ACE inhibitors); sulfonylureas (with metformin if needed) for diabetes [171]; and low-cost statins for cholesterol control.[2] Indeed, it has been estimated that the relatively low-cost combination of aspirin and beta-blockers after acute myocardial infarction could prevent about 300,000 deaths due to ischemic heart disease and stroke in low- and middle-income countries in the year 2020 if coverage were increased from 30–40 percent to 85 percent of the patient population.[ 2,172] It will be important for health care personnel who administer and monitor antihypertensive drug treatments to be aware of the side effects of these drugs.

Hypertension deserves particular attention in developing countries because of its prominence as a risk factor for cardio- and cerebrovascular disease. Community-based hypertension control programs in rural Japan [173] and urban China [104] (see Box 10-2) have been shown to reduce stroke incidence, suggesting that similar programs would be both feasible and effective in many developing countries. Patient education should be a primary objective of such community-based programs, to ensure proper and continuous use of antihypertensive medication.[79,80] Sample guidelines for patient education at the primary care level, developed by the Hypertension Society of Southern Africa, appear in Box 10-3.

According to current guidelines, patients with a first cerebrovascular event due to cardioembolism should be treated with oral anticoagulants if there are no contraindications. Patients with atherothrombotic strokes should typically receive antiplatelet agents. For the best-studied agent, aspirin, the currently rec-

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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BOX 10-2 Stroke Prevention in Urban China

Stroke incidence has risen rapidly in the PRC over the past two decades, along with risk factors such as hypertension and smoking. Public understanding of healthy lifestyles appears to be poor; however, researchers have reason to believe that community-level efforts to reduce risk factors for stroke could be effective. Medical scientists from the Beijing Neurosurgical Institute, along with collaborators at the University of Washington, Seattle, established pilot intervention programs in seven Chinese cities to provide health education and treatment for hypertension, heart disease, and diabetes.

Beginning in May 1997, two geographically separated communities of approximately 10,000 people within each of the cities were selected as either intervention or control populations. Within each community, a cohort of 2,700 subjects age 35 or older and free of stroke were selected as subjects or controls for medical intervention. In the intervention community, subjects were treated for hypertension, diabetes, and heart disease as considered appropriate by their physicians, and a preventive education program was provided for all 10,000 residents.

After 3.5 years of intervention, the incidence rates for fatal and nonfatal stroke, as well as for ischemic and hemorrhagic stroke, were found to be significantly lower in the intervention cohort than in the control cohort. The. sharp reduction in stroke incidence appeared to be due primarily to a blunting of the expected rise in hypertension as residents aged, as well as to earlier treatment of hypertension, especially borderline cases. Increased general health awareness and knowledge derived from health education may also have played a role in preventing some individuals from developing hypertension.

Source: [104]

ommended dose is 50–325 mg daily.[174] Other anticoagulant drugs require blood monitoring and standardization in dosing (which increases the overall cost of administration) to control adverse side effects, yet some may prove cost-effective in certain developing-country settings for the prevention of stroke recurrence or full stroke following a TIA. However, aspirin appears to be the more cost-effective option in many cases.[175]

Aspirin has been shown in clinical studies to reduce the relative risk of stroke or death by approximately 20 percent per year after a TIA or minor ischemic stroke.[168,176] This translates into an absolute benefit of 12 strokes prevented per 1000 patients treated for 1 year, at a cost of approximately one intracerebral hemorrhage. Recently, three other antiplatelet agents—ticlopidine, clopidogrel, and a combination of aspirin and extended-release dipyridamole—have been shown to be effective for stroke prevention. Ticlopidine and clopidogrel appear to be slightly more effective than aspirin in clinical trials, but they are also more

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×

BOX 10-3 Education Guidelines for Patients with Hypertension

The following guidelines were developed by the Hypertension Society of Southern Africa, and endorsed by the Medical Association of South Africa and the Medical Research Council:

  • Teach patients the distinction between having a risk factor (hypertension) and having a disease.

  • Teach patients to understand hypertension and its consequences if not treated adequately.

  • Inform patients of their blood pressure reading at every visit, and tell them whether it is controlled or otherwise.

  • Teach patients to tell any medical practitioner they visit about their hypertension and what drugs they are taking, and encourage them to request a blood pressure measurement at each visit.

  • Tell patients the name and dose of the drug(s) they are prescribed, the frequency of dosing, and the necessity of regular ongoing use. Ensure that patients know this at every visit.

  • Provide reassurance as needed for patients with mild hypertension who have excess fear of stroke or other consequences of hypertension.

Source: [177]

expensive.[57,176] Cost comparisons, safety profiles, and availability will influence the choice of antiplatelet agent for patients in developing countries.

While drug combinations such as aspirin and beta-blockers may currently provide cost-effective prevention of stroke in emerging market economies, more expensive drugs, such as the cholesterol-lowering statins and ACE inhibitors, may not prove cost-effective for years to come. One means of increasing access to such useful but costly medications may be to negotiate pricing strategies and partnerships with pharmaceutical manufacturers (either individually or through collective agreements), which could supply a range of commonly prescribed medicines at reduced cost. For example, essential medicines for treating hypertension and hyperlipidemia could be offered in economical “vascular packages ” that could be widely accessible.[2] Recognizing that the secondary prevention of hypertension, diabetes, and a variety of other comorbid conditions is key to stroke prevention, the committee makes the following recommendation.

Recommendation 10-6. Treatment, including essential medications, should be made available through primary care to all individuals with conditions such as hypertension, diabetes, and postpartum cerebral venous thrombosis that represent risk factors for stroke, as well as for those who have experienced TIAs. Medicines of proven cost-effectiveness should be used whenever possible; pricing strategies and partnerships should be undertaken to enable resource-limited developing countries to purchase costly essential medications.

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
×
Treatment

Stroke is a particularly challenging condition to treat because of its sudden onset and the rapid tissue damage that ensues. Because of these limitations, the best option for managing stroke in developing countries is prevention, both of first stroke and of recurrence. A particularly thorny issue in the treatment of acute stroke is the need to diagnose stroke subtype, because existing treatments for ischemic stroke, such as aspirin, heparin, and recombinant tissueplasminogen activator (rtPA) (see below), can worsen the outcome of hemorrhagic stroke and vice versa.[8] Currently, the only reliable means of diagnosing stroke subtype is through the use of computed tomography (CT) brain scans, a rare option in developing countries.[15,178] Accurate, affordable clinical methods for diagnosing stroke subtype are thus urgently needed for use by the majority of the world's population.

The long search for a drug that can dissolve vascular obstruction and restore cerebral circulation following ischemic stroke appears to offer some promise with the success of rtPA in a clinical trial conducted by the National Institute of Neurological Disorders and Stroke. Patients suffering from an ischemic stroke who were treated with rtPA were significantly more likely to have minimal or no disability at 3 months after treatment than were those given placebos.[179] However, another large-scale study, conducted by the European Cooperative Acute Stroke Study (ECASS), did not show a significant benefit as compared with controls.[180] Although promising, not all countries have approved the use of rtPA, and further studies are necessary. For developing countries, there are additional limitations that may make this treatment option a lower priority, including (1) the need to begin treatment within 3 hours of stroke onset, which may limit use of rtPA where the technology is too distant and/or transportation is unavailable; (2) the limited availability of expensive CT scanning machines; (3) the limited availability and relatively high cost of rtPA; (4) the limited availability of special stroke teams with expertise in the use of the drug; (5) and the need to manage complications, especially the increased risk of hemorrhage.[181]

The above limitations apply to most of the available stroke treatment methods. These limitations point to areas in which additional resources for health spending would contribute to improvements in access to diagnostic tools, the availability of specialists who can interpret their results, and a better supply of cost-effective drug treatments for stroke.

Rehabilitation

The rehabilitation process has six major elements: (1) preventing, recognizing, and managing comorbid illnesses and medical complications; (2) providing training for maximum independence; (3) facilitating maximum psychosocial coping and adaptation by patient and family; (4) preventing secondary disability by promoting community reintegration, including resumption of home, family, recreational, and vocational activities; (5) enhancing quality of life in view of any residual disability; and (6) preventing recurrent stroke and other

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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vascular conditions, such as myocardial infarction, that occur with increased frequency in patients with stroke.[182] Because depression and other mental disorders rank among the most prevalent and disabling consequences of strokes of all severity, mental health care represents an important component of stroke rehabilitation (see Chapter 10).[167,183,184]

No conclusive evidence demonstrates the cost-effectiveness of stroke rehabilitation in developed or developing countries. Where resources are limited, support for preventive efforts is a priority. However, if local communities have rehabilitation programs for other disabling conditions such as cerebral palsy or mental retardation, coordination and integration of stroke-related rehabilitation could prove to be cost-effective, (see Chapter 5 for detailed information about community-based rehabilitation). Research on home-based rehabilitation could also yield promising strategies for cost-effetive post-stroke care.

Recommendation 10-7. Existing community-based rehabilitation programs for developmental disabilities should explore cost-effective extension of care for stroke-related disabilities. Research on rehabilitation approaches in developing countries should examine home-based strategies and other potentially cost-effective means of supporting stroke patients and their families.

Cost Analysis

Determination of the monetary costs of mortality, morbidity, disability, and handicap due to stroke is difficult, if not impossible, and many such studies performed to date have serious inadequacies. The principles of costing illness emphasize the importance of incorporating estimates of the direct costs to health services, social agencies, and patients, as well as the indirect costs to society and patients due to lost productivity and distress.[185] When prevention and treatment strategies involve drugs, their cost-effectiveness depends on the costs of these medications and their availability at the community level.

The costs of stroke have been studied in many countries, all developed. These studies have verified the huge economic impact of stroke, revealing that stroke-related costs account for 3–5 percent of the annual health care budget in some industrialized countries.[186,187] Because of the high rate of mortality associated with stroke and the equally high level of disability, prevention is the most cost-effective approach, although some forms of prevention—particularly medications such as cholesterol-lowering drugs—are unlikely to prove cost-effective in developing countries at this time (a sample cost analysis for various drug treatments for the prevention of stroke in the United States appears in Box 10-4). More promising strategies for developing countries lie in the promotion of behavioral changes (smoking cessation, fat- and sodium-reduced diets, lipid-lowering diets, physical activity, and weight reduction), as well as inexpensive drug interventions (lipid-lowering medications, aspirin, beta-blockers) that have been demonstrated to be highly cost-effective in developed countries.[168,175]

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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While several antihypertensive drugs appear likely to be cost-effective for preventing stroke even where health care resources are scarce, the initial investment required to purchase them may be prohibitive in some low-income settings. For many developing countries, the only cost-effective alternatives to drug therapy for lowering blood pressure are interventions such as sodium restriction, potasium supplementation, fish-oil supplementation, and a combination of these therapies with weight reduction and increased exercise over a longer period.[168] There is also evidence that a paramedical intervention program, including advice on diet, stress reduction, exercise, and smoking cessation, could result in net savings in drug costs among treated hypertensive patients: it is estimated that 25 percent of patients could cease drug therapy, and another 25 percent could reduce their drug requirements by half.[168,175] Dietary change may turn out to be the primary means of controlling hypertension in the developing world, where the cost of drug treatment for hypertension could amount to up to 5 percent of total health care costs.[168]

Where health care resources are limited, research is needed to ensure optimal allocation of funds and human capital to interventions for stroke. The Asia Pacific Consensus Forum on Stroke Management has pointed out the relevance of developing databases for use in assessing and evaluating (1) the needs of the community, (2) the accessibility of stroke care, (3) the effectiveness of acute stroke care, (4) the effectiveness of rehabilitation, (5) the adequacy of education programs, and (6) the key indicators of process and outcome.[58,90]

Recommendation 10-8. Research to assess local needs for stroke prevention, treatment, and rehabilitation should be conducted in developing countries to inform the planning and allocation of health care resources aimed at reducing the burden of illness associated with stroke. International support for such efforts should include the development of information technology and databases to aid research and multinational collaboration.

CAPACITY

This chapter has emphasized that prevention is key to reducing death and disability due to stroke. At the community level, health care workers and other paramedical personnel should provide basic education regarding stroke risk factors and promote a healthy diet, smoking cessation, and other lifestyle modifications, as well as regular checkups to test for hypertension and diabetes. Guidelines for accomplishing these tasks have been developed by WHO and PAHO [188]; training programs should be established to distribute such

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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BOX 10-4 Sample Cost Analysis of Medications for Stroke Prevention

The following figures estimate the benefit and cost of providing appropriate stroke-preventive drugs for 1 year to a population of 1 million people in the United States, who would otherwise be expected to experience 2,400 strokes. The total cost of such an initiative was estimated to be $2.6 million; however, the cost of treatment and rehabilitation for the strokes prevented was estimated to be $25 million. Thus, according to this scenario, an annual investment of $1 in stroke-preventing medicines would be expected to result in a savings of nearly $10.

Drug Type

Cost/Patient/Year (US$)

Strokes Prevented

Antihypertensive (bendrofluazide)

132

21

Anticoagulant (warfarin)

85

70

Anticholesterol (statin)

81

500

Antiplatelet (aspirin)

80

14

Source: [39]

information to health care workers. Primary health care workers, nurses, and physicians play an important role in detecting, diagnosing, and treating hypertension, hypercholesterolemia, and atrial fibrillation, and in ensuring compliance with treatment. Their training, too, should emphasize the importance of stroke prevention through both patient education and the management of conditions known to be risk factors for stroke.

Recommendation 10-9. Training guidelines for stroke prevention should be developed and established as part of basic education for both primary medical and paramedical personnel in developing countries. Medical school curricula for both general practitioners and neurological and psychiatric specialists should include training in the use of diagnostic tools and assessment methods that reflect the local and regional presentation of stroke in both primary care and secondary/tertiary care centers, as well as knowledge about local pathways to care for stroke.

Beyond primary care, key resources for stroke services include stroke units in major hospitals, rehabilitation facilities, and post-stroke community support

Suggested Citation:"10 Stroke." Institute of Medicine. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World. Washington, DC: The National Academies Press. doi: 10.17226/10111.
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programs.[189] While such amenities are likely to serve a small minority of stroke patients in a developing country, they can play an important role in the development and introduction of appropriate, cost-effective methods and technology for stroke prevention, treatment, and rehabilitation.[ 29,190] Facilities such as national and regional training and research centers proposed elsewhere in this report (see Chapter 4) should provide training and employment for greater numbers of neurologists, who could establish programs of secondary and tertiary stroke care.

Recommendation 10-10. Regional and national centers for training and research on brain disorders should include facilities and specialists for secondary and tertiary stroke care, research on locally appropriate interventions for stroke, and expert support for stroke-related training of primary health care workers.

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4. K. Asplund, R. Bonita, K. Kuulasmaa, A-M Rajakangas, V. Feigin, H. Schaedlich, et al. Multinational comparisons of stroke epidemiology. Evaluation of case ascertainment in the WHO MONICA study. Stroke 26:355–360, 1995.

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×

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Brain disorders—neurological, psychiatric, and developmental—now affect at least 250 million people in the developing world, and this number is expected to rise as life expectancy increases. Yet public and private health systems in developing countries have paid relatively little attention to brain disorders. The negative attitudes, prejudice, and stigma that often surround many of these disorders have contributed to this neglect.

Lacking proper diagnosis and treatment, millions of individual lives are lost to disability and death. Such conditions exact both personal and economic costs on families, communities, and nations. The report describes the causes and risk factors associated with brain disorders. It focuses on six representative brain disorders that are prevalent in developing countries: developmental disabilities, epilepsy, schizophrenia, bipolar disorder, depression, and stroke.

The report makes detailed recommendations of ways to reduce the toll exacted by these six disorders. In broader strokes, the report also proposes six major strategies toward reducing the overall burden of brain disorders in the developing world.

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