The Global Burden of Cardiovascular Disease

Stephanie Ounpuu, PhD, RD; Sonia Anand, MD, FRCP(C); Salim Yusuf, MBBS, DPhil, FRCP(UK)

Disclosures

January 24, 2002

Introduction

In 1990 ischemic heart disease (IHD) was the leading cause of mortality and the fifth leading cause of morbidity in the world. Over the next few decades IHD rates are expected to double, and with this, IHD will become the leading cause of both morbidity and mortality worldwide. However, whereas at the end of the 20th century more than 60% of the global burden of IHD already occurs in the developing countries, 82% of the anticipated increase in mortality and 89% of the increase in morbidity will be experienced in these regions.[1]

There are at least 3 contributing factors that account for the increased incidence of cardiovascular disease (CVD) in developing countries:

  • The successes of worldwide public health efforts have resulted in the current trend of decreasing mortality from acute infectious diseases, and this will result in a higher proportion of individuals reaching middle and old age.

  • Current worldwide economic development leads to increasing urbanization, and with this the aging population will be exposed to the higher levels of risk factors that accompany the lifestyle and socioeconomic changes associated with urbanization. Therefore, both the degree and the duration of exposure to the CVD risk factors can be expected to increase as a result of higher risk factor levels coupled with a longer life expectancy.

  • The special susceptibilities of certain populations (eg, due to specific genes), compared with Western populations, may lead to a greater impact on clinical events (Figure 1).

Relationship of genetic background to clinical events, worldwide.

Changes in diet, physical activity, and tobacco use have been observed in countries undergoing transition. Evolution in dietary patterns includes increased consumption of higher-fat foods, a shift from plant to animal protein, and shifts toward refined carbohydrates and sweets[2,3]; these changes appear to be accelerated by urbanization.[2,4] For example, food disappearance data[5] indicate that between 1967 and 1997 in both Asia and the Middle Eastern Crescent, per capita availability of animal protein and fat more than doubled. In Malaysia, while total calories available increased by 24% during this time period, calories available from animal fat increased by 164%. Data from the China Health and Nutrition Surveys indicate that between 1989 and 1991, the prevalence of relatively high fat consumption was increased among adults living in urban areas and among higher-income groups. In Chinese urban areas, 46% of high-income participants, 38% of middle-income participants, and 20% of low-income participants consumed more than 30% energy as fat, compared with 25%, 19%, and 14% of high-, middle-, and low-income participants in rural areas, respectively.[2]

Differences were also observed in activity patterns. Between 1989 and 1991, the prevalence of sedentary activity patterns increased substantially among urban Chinese residents in all income groups, a trend not observed among rural residents. Over the same time period, an increased prevalence of overweight was observed in the high- and middle-income groups but not in the low-income group.[6] In India a higher prevalence of both sedentary lifestyle and obesity in urban compared with rural communities has also been observed,[7] and national nutrition surveys conducted in Brazil have demonstrated a striking increase in the prevalence of overweight and obesity (from 21% of the population in 1974-75 to 33% in 1989), especially among those with higher incomes and urban residence.[8]

Populations in transitional countries account for approximately 85% of the 1.15 billion smokers worldwide,[9] and the trends toward increased tobacco consumption observed in most transitional countries contrast with trends toward decreased smoking rates observed in most developed countries. In the United States, for example, smoking rates have decreased from over 40% of all adults in the 1960s to approximately 23% in 1997. In contrast, overall prevalence of smoking among adult men in developing countries is currently approximately 48%, and is increasing by about 3.4% per year.[9] Results of the 1996 National Prevalence Survey in China indicated that more than 60% of adult men in China currently smoke.[10]

These trends in smoking rates will lead to large increases in chronic disease mortality attributable to tobacco. Indeed it is estimated that annual deaths due to smoking will increase from about 1 million worldwide in 1995 to over 7 million in 2025.[11] During this period, tobacco-related mortality will rise from about 1% to 13% of total mortality in India, and from 14% to 23% of total mortality in the formerly socialist economies of Eastern Europe.[12] The World Health Organization predicts that if the current patterns continue, by 2050 smoking will cause 10 million deaths annually, with greater than 70% of these deaths occurring in developing countries.[9]

Whereas the behavioral responses to the global changes in the socioeconomic environment are remarkably consistent across cultures, the genetically determined metabolic responses to the resulting changes in CVD risk profiles may vary in specific populations. For example, the "thrifty gene hypothesis" describes a process of selective survival, whereby a population that was intermittently exposed to adverse environmental conditions and associated famine acquired a genetically based coping mechanism. According to this hypothesis, a lack of insulin sensitivity in the skeletal muscle may be beneficial to ensure adequate blood glucose levels for the brain in conditions of limited calorie intake and demanding physical challenges. However, as the subpopulation that has acquired the gene during years in the wilderness moves into increasingly urban settings and begins to eat a lot more, the metabolic consequences of the gene's presence may lead to a less desirable response, such as varying degrees of glucose intolerance and hyperinsulinemia.

Such gene-environment interactions may relate to obesity and atherosclerosis (due to selection of a gene that increases the efficiency of fat storage), higher blood pressure levels (eg, salt retention or sensitivity genes), or higher homocysteine levels (due to higher consumption of meats and lower consumption of vegetables interacting with various genes that affect homocysteine synthesis or breakdown).

Studies from Canada, the United Kingdom, Singapore, South Africa, and Mauritius have consistently demonstrated variation in chronic disease rates by ethnicity. Our analysis of 2.6 million deaths from the Canadian National Mortality Database, for example, demonstrated that Canadians of South Asian background have a high rate of CHD mortality but low cancer mortality, whereas Chinese Canadians have low CHD mortality and relatively higher cancer mortality -- and that the rates of both conditions are high among European Canadians.[13,14]

The extent to which these variations by ethnicity are due to genetic factors or environmental factors remains unclear. Recent studies have identified candidate genes that may correlate with CVD and with its risk factors, such as obesity, plasma lipoproteins, elevated blood pressure, and elevated blood glucose; however, the relative frequencies of various genes among different ethnic groups is unknown.

In order to overcome some of the limitations of the currently available data and to obtain standardized information across ethnic groups both within and across many different countries, we have been involved in facilitating 2 studies. We have just completed SHARE (Study of Health Assessment and Risk in Ethnic groups),[15] in which atherosclerosis, clinical CVD, and traditional and emerging risk factors were measured in 997 randomly chosen individuals of 3 ethnic groups (South Asian, Chinese, and European Canadian). Preliminary data indicate marked differences in lipid profile, glucose abnormalities, coagulation parameters, and homocysteine levels between the 3 groups. Although within each ethnic group the degree of carotid atherosclerosis predicted clinical CVD, the relationship varied (steepest among South Asians, least steep among Chinese, intermediate among European Canadians). After controlling for all risk factors and degree of atherosclerosis, ethnicity remained an independent risk factor for presence and/or degree of CVD.

In a second study, a group of scientists is collaborating in a large international, multicenter, incident case-control study (INTER-HEART). Approximately 13,000 incident cases of acute myocardial infarction in men and women who are or will be admitted to the coronary care unit in the multicenters and a similar number of age- and sex-matched controls will be enrolled in the study. The case-control design will enable the determination of the relative importance for both conventional and emerging risk factors in acute nonfatal myocardial infarction. An understanding of the risk factors that lead to the development of CVD in multiple countries is required in order to meet calls to develop global strategies for prevention.[16] Therefore, subjects will be recruited from Eastern and Western Europe, Russia, the Middle Eastern Crescent, South Asia, Southeast Asia, China, Latin America, and North America. INTER-HEART has received sponsorship from the World Health Organization and the World Heart Federation. Data collection for the vanguard phase began in February 1999 for a 1-year period, during which 4000 subjects were enrolled from 47 countries. Full data collection begins in April 2000 and will be complete by October 2003.

These studies are initial steps toward exploring the causes of CVD in different populations across the world. The findings undoubtedly must be explored in further detail in prospective large cohort studies that combine a range of methodologies (eg, nutrition, lifestyle factors, biological markers, and genetic variations) in several of the participating countries. Such an approach will lead to valuable information upon which a global strategy for CVD prevention can be developed that is both ethnically and regionally sensitive.[17]

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