Although it is not surprising that cardiovascular disease (CVD) is the leading cause of death worldwide because of its predominance in developed countries, it is surprising that CVD ranked second as a cause of death in all developing countries in 1990, with its burden almost equal to that of the leading cause-lower respiratory infections (see Table A-1). In fact, given the falling rates of infectious and parasitic diseases and the increasing rates of CVD in developing countries, CVD was most likely the developing world's leading cause of death by the mid- 1990s. If ignored, this epidemic will increase drastically in the coming years.
Not only is CVD the largest cause of mortality in older age groups and in men, it is also a very significant contributor to mortality in persons of economically productive ages (i.e., 30-69 years) and in women (see Table A-2). Evidence shows that in 1990, CVD contributed to three times as many deaths worldwide in 30- to 69-year-olds as did infectious and parasitic diseases. This is true for both men and women, and it is true for all regions of the world except Sub-Saharan Africa. In this region, the numbers of deaths from CVD and infectious or parasitic diseases were about equal in 1990, and it is possible that CVD will soon dominate mortality in this region as well. This burden of disease and death in the economically most productive age stratum has important consequences for health care resources and for the economy in general, as indicated in Chapter 2.
Diseases affecting the circulatory system are present during all stages of a country's development. Whereas CVD has been the dominant cause of death in developed countries for more than half a century, it is also emerging as the
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Appendix A Five Steps for Setting Research Priorities STEP 1: DETERMINE THE SIZE OF THE CVD BURDEN Although it is not surprising that cardiovascular disease (CVD) is the leading cause of death worldwide because of its predominance in developed countries, it is surprising that CVD ranked second as a cause of death in all developing countries in 1990, with its burden almost equal to that of the leading cause-lower respiratory infections (see Table A-1). In fact, given the falling rates of infectious and parasitic diseases and the increasing rates of CVD in developing countries, CVD was most likely the developing world's leading cause of death by the mid- 1990s. If ignored, this epidemic will increase drastically in the coming years. Not only is CVD the largest cause of mortality in older age groups and in men, it is also a very significant contributor to mortality in persons of economically productive ages (i.e., 30-69 years) and in women (see Table A-2). Evidence shows that in 1990, CVD contributed to three times as many deaths worldwide in 30- to 69-year-olds as did infectious and parasitic diseases. This is true for both men and women, and it is true for all regions of the world except Sub-Saharan Africa. In this region, the numbers of deaths from CVD and infectious or parasitic diseases were about equal in 1990, and it is possible that CVD will soon dominate mortality in this region as well. This burden of disease and death in the economically most productive age stratum has important consequences for health care resources and for the economy in general, as indicated in Chapter 2. STEP 2: IDENTIFY THE REASONS FOR THE CVD BURDEN Diseases affecting the circulatory system are present during all stages of a country's development. Whereas CVD has been the dominant cause of death in developed countries for more than half a century, it is also emerging as the
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dominant disease in developing countries. Although evidence from developed countries demonstrates that the control of CVD can be approached with measurable benefit through interventions at the individual, community, and national levels, this knowledge and experience have yet to be systematically applied in developing country populations. Thus, one reason the CVD burden persists and will increase in developing countries is because the potential implementation of intervention programs is hampered by the lack of appropriate awareness of cost-effective CVD control options and by concerns that such investments may detract from investments in communicable disease control and childhood, maternal, and reproductive health. TABLE A-1 Ten Leading Causes of Death for 1990 Rank Developed Regions Total Deaths (thousands) Developing Regions Total Deaths (thousands) 1 Ischemic heart disease 2,695 Lower respiratory infections 3.915 2 Cerebrovascular disease 1,427 Ischemic heart disease 3,565 3 Trachea, bronchus, and lung cancer 523 Cerebrovascular disease 2,954 4 Lower respiratory infections 385 Diarrheal diseases 2,940 5 Chronic obstructive pulmonary disease 324 Conditions arising during the perinatal period 2,361 6 Colon and rectum cancers 277 Tuberculosis 1,922 7 Stomach cancer 241 Chronic obstructive pulmonary disease 1,887 8 Road traffic accidents 222 Measles 1,058 9 Self-inflicted injuries 193 Malaria 856 10 Diabetes mellitus 176 Road traffic accidents 777 Total deaths 10,912 Total deaths 39,554 SOURCE: Murray and Lopez, 1996. Another reason for the persistence of the emerging epidemic of CVD in low-and middle-income populations in developing countries is their increasing adoption of behaviors and life-styles that are known to elevate CVD risk. As indicated in Chapter 2, evidence suggests that the prevalence of established CVD risk factors such as tobacco use, elevated blood pressure, high saturated fat intake, obesity, and diabetes is increasing in these populations. The increasing rates of cigarette smoking alone are expected to increase CVD deaths in developing countries more than 18-fold in the next 22 years. These data are projected in
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Table A-3. By the year 2020, the number of CVD deaths attributable to tobacco use is expected to surpass 2.5 million annually. A third reason for the emerging epidemic of CVD in developing countries is largely unavoidable: the aging of populations due to declining fertility and the reduction in infant and childhood mortality (see Chapters 1 and 2). In summary, the emerging epidemic of CVD in low- and middle-income country populations can be attributed to demographic change, rapid adoption of life-styles and habits associated with elevated CVD risk, and lack of current investment in intervention programs directed to the reduction and prevention of CVD risk factors and to the treatment and control of existing cases. STEP 3: EVALUATE THE ADEQUACY OF THE CURRENT KNOWLEDGE BASE Although much is known in developed countries about the distribution and influence of major risk factors for CVD, and lessons in prevention and treatment continue to be learned, there is little experience in applying this rich base of knowledge to the populations of low-and middle-income countries. Data on the nature, extent, and trends in disease occurrence and prevalence of major CVD risk factors are lacking for most regions of the developing world. TABLE A-2 Deaths (thousands) Due to CVD and to Infectious and Parasitic Disease (IPD) in 30- to 69-Year-Olds by Sex and Region-1990 Men Women Region CVD IPD CVD IPD Established market economies 483 42 227 12 Formerly socialist economies 263 20 163 6 India 611 429 481 240 China 576 158 439 89 Other Asian and Pacific Island countries 289 147 226 140 Sub-Saharan Africa 183 215 211 228 Latin American and Caribbean countries 186 62 147 48 Middle Eastern Crescent 285 83 215 85 Worldwide 3,028 1,128 2,201 798 SOURCE: Murray and Lopez, 1996.
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TABLE A-3 Estimated Number of CVD Deaths (thousands) Worldwide Attributable to Cigarette Smoking and Percentage of Total Estimated Global Deaths-1990, 2000, 2010, and 2020 1990 2000 2010 2020 Deaths attributable to cigarette smoking 955 1,399 1,931 2,613 Percentage of total deaths 1.9 2.5 3.2 3.8 SOURCE: Ad Hoc Committee on Health Research Relating to Future Intervention Options, 1996. As a result, little is known about differences in CVD risk factors, clinical presentation, and outcomes in most developing world populations. Such differences may reflect variations in the prevalence of major established risk factors such as cigarette smoking, high blood pressure, hypercholesterolemia, and obesity, and possibly in the genetic predisposition to these risk factors. They may also reflect variations in unidentified risk factors. If governments and health providers are to respond adequately to the challenge of the emerging epidemic of CVD in developing countries, the committee believes they will need reliable data on the current and projected burden of CVD in their regions, as well as information on what they can do to reduce it. Many of the recommendations in this report, therefore, focus on epidemiologic data needs and on assessing the applicability of established CVD interventions in developing country populations. Such knowledge can be of critical importance, either confirming that approaches used elsewhere can be applied effectively or demonstrating that adaptation will be required. STEP 4: EVALUATE THE PROMISE OF R&D EFFORTS As Chapters 1 and 2 demonstrate, epidemiologic studies in developed countries provide abundant evidence for the preventability of CVD. In general, two broad strategies have been employed for CVD prevention in developed countries, namely, the high-risk approach and the population (public health) approach. The high-risk approach seeks to identify those with high levels of CVD risk factors and to treat these high-risk individuals intensively to reduce their risk. Although this approach can be effective for the individuals identified, it has limited the opportunity to reduce the population-wide burden of disease, since the large number of cases is not found in the small proportion at highest risk, but rather in those nearer the center of the distribution. Therefore, the population approach proposes to shift the entire distribution of CVD risk factors toward lower risk, so that substantial reduction of the overall population risk can be realized. Depending on circumstance (see Chapter 2), both strategies can be effec-
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tive and many developed country populations use a combination of high-risk and population strategies. Prevention strategies can be further divided into three categories from the perspective of risk factors: (1) ''primordial prevention" is directed toward prevention of the risk factors themselves; (2) "primary prevention" focuses on reducing the existing risk factors (e.g., lowering blood pressure or the prevalence of cigarette smoking); and (3) "secondary prevention" is directed toward early detection and management of existing clinical disease (e.g., guidelines for management of acute myocardial infarction or heart attack). Although primordial prevention strategies directed toward modifiable risk factors such as cigarette smoking, hypertension, and obesity have been shown to be effective in developed country populations, they have yet to be systematically investigated in developing countries but offer promise as cost-effective approaches. For its part, primary prevention of CVD—which has been shown in developed countries to be effective in randomized trials for elevated low-density lipoprotein (LDL) cholesterol, high-fat or cholesterol diets, hypertension, and especially cessation of cigarette smoking—should be assessed in developing world populations, particularly when low-cost interventions are sought or high-risk subgroups are targeted. Secondary prevention or case management strategies have been investigated extensively in patients in developed countries during both acute events and later phases of coronary heart disease and cerebrovascular disease. Interventions range from relatively inexpensive steps, such as behavioral risk factor control strategies (e.g., smoking cessation, lipid-lowering diet, physical activity, and weight reduction), to more expensive forms of technology (e.g., lipid-lowering drugs, aspirin, beta-blockers, and estrogens), to much more expensive technologies (e.g., thrombolytic therapies, automated internal defibrillators, coronary angiography with or without angioplasty and/or stent placement, coronary bypass surgery, cardiac transplantation). Experience in developed country settings shows that effective interventions need not be costly. For example, marked improvements in survival from acute myocardial infarction after 1980 were largely due to the increasing use of aspirin, low-cost beta-blockers, and to a lesser extent, newer and more expensive clot-dissolving drugs. As indicated in Chapter 2 (Table 2-3), the relatively low-cost combination of aspirin and beta-blockers alone could prevent more than 210,000 deaths annually due to ischemic heart disease (IHD) and stroke in developing countries by the year 2020. In summary, although many interventions with behavioral and inexpensive technologies are highly cost-effective in case management in developed countries, there is a need to assess the feasibility and cost-effectiveness of these management strategies in developing country settings. This same need extends to proven primordial and primary prevention approaches.
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STEP 5: ASSESS THE ADEQUACY OF THE CURRENT LEVEL OF EFFORT Chapters 3 and 4 of this report address current patterns of CVD prevention and care and current levels and types of supporting R&D in developing countries. The message of these chapters is clear and consistent: few international donors or developing country governments recognize the importance of the emerging CVD epidemic in the developing world. In addition, in the majority of countries that have taken initial steps to address the epidemic, the focus has been on technology development, including building and supporting urban care facilities for diagnosis and treatment of CVD. There is little to no emphasis on developing, assessing, or implementing interventions for primordial and primary prevention in developing world populations. In the very few instances where developing country governments have emphasized prevention—see, for example, the successful case study of Zambia cited in Chapter 3—the resulting health benefits have been profound. The committee's recommendations represent a synthesis of the evidence presented in this report and a distillation of the more numerous recommendations detailed in Chapter 5. The committee hopes that these recommendations will result in prompt and effective action to control CVD in developing countries, and that this action will be assisted by the Forum on International Health R&D and by other international donors, national governments, and professional organizations. The potential health and economic benefits of effectively engaging in the global fight against CVD are many. To continue as is, with the current inadequate level of effort, invites significant peril. An alternative future is possible, in which developing countries invest early enough to prevent the enormous costs of a major epidemic of CVD such as that experienced by developed countries in the twentieth century.