The global rise in CVD is the result of an unprecedented transformation in the causes of morbidity and mortality during the twentieth and twenty-first centuries. Known as the epidemiologic transition, this shift is driven by industrialization, urbanization, and associated lifestyle changes and is taking place in every part of the world among all races, ethnic groups, and cultures. The transition is divided into four basic stages: pestilence and famine, receding pandemics, degenerative and human-made diseases, and delayed degenerative diseases. A fifth stage, characterized by an epidemic of inactivity and obesity, may be emerging in some countries (Table 225-1).
Table 225–1. Five Stages of the Epidemiologic Transition |Favorite Table|Download (.pdf)
Table 225–1. Five Stages of the Epidemiologic Transition
|Stage||Description||Deaths Related to CVD, %||Predominant CVD Type|
|Pestilence and famine||Predominance of malnutrition and infectious diseases as causes of death; high rates of infant and child mortality; low mean life expectancy||<10||Rheumatic heart disease, cardiomopathies caused by infection and malnutrition|
|Receding pandemics||Improvements in nutrition and public health lead to decrease in rates of deaths related to malnutrition and infection; precipitous decline in infant and child mortality rates||10–35||Rheumatic valvular disease, hypertension, CHD, and stroke (predominantly hemorrhagic)|
|Degenerative and human-made diseases||Increased fat and caloric intake and decrease in physical activity lead to emergence of hypertension and atherosclerosis; with increase in life expectancy, mortality from chronic, noncommunicable diseases exceeds mortality from malnutrition and infectious disease||35–65||CHD and stroke (ischemic and hemorrhagic)|
|Delayed degenerative diseases||CVD and cancer are the major causes of morbidity and mortality; better treatment and prevention efforts help avoid deaths among those with disease and delay primary events; age-adjusted CVD morality rate declines; CVD affecting older and older individuals||40–50||CHD, stroke, and congestive heart failure|
|Inactivity and obesity||Overweight and obesity increase at alarming rate; diabetes and hypertension increase; decline in smoking rates levels off; a minority of the population meets physical activity recommendations||Possible reversal of age-adjusted declines in mortality||CHD, stroke, and congestive heart failure, peripheral vascular disease|
Malnutrition, infectious diseases, and high infant and child mortality rates that are offset by high fertility mark the age of pestilence and famine. Tuberculosis, dysentery, cholera, and influenza are often fatal, resulting in a mean life expectancy of about 30 years. Cardiovascular disease, which accounts for less than 10% of deaths, takes the form of rheumatic heart disease and cardiomyopathies due to infection and malnutrition. Approximately 10% of the world's population remains in the age of pestilence and famine.
Per capita income and life expectancy increase during the age of receding pandemics as the emergence of public health systems, cleaner water supplies, and improved nutrition combine to drive down deaths from infectious disease and malnutrition. Infant and childhood mortality rates also decline, but deaths due to CVD increase to between 10% and 35% of all deaths. Rheumatic valvular disease, hypertension, coronary heart disease, and stroke are the predominant forms of CVD. Almost 40% of the world's population is currently in this stage.
The age of degenerative and human-made diseases is distinguished by mortality from noncommunicable diseases—primarily CVD—surpassing mortality from malnutrition and infectious diseases. Caloric intake, particularly from animal fat, increases. Coronary heart disease and stroke are prevalent, and 35%–65% of all deaths can be traced to CVD. Typically, the rate of CHD deaths exceeds that of stroke by a ratio of 2:1 to 3:1. During this period, average life expectancy surpasses 50 years. Roughly 35% of the world's population falls into this category.
In the age of delayed degenerative diseases, CVD and cancer remain the major causes of morbidity and mortality, with CVD accounting for 40% of all deaths. However, age-adjusted CVD mortality declines, aided by preventive strategies such as smoking cessation programs and effective blood pressure control, acute hospital management, and technological advances such as the availability of bypass surgery. Coronary heart disease (CHD), stroke, and congestive heart failure are the primary forms of CVD. About 15% of the world's population is now in the age of delayed degenerative diseases or is exiting this age and moving into the fifth stage of the epidemiologic transition.
In the industrialized world, physical activity continues to decline while total caloric intake increases. The resulting epidemic of overweight and obesity may signal the start of the age of inactivity and obesity. Rates of Type 2 diabetes mellitus, hypertension, and lipid abnormalities are on the rise, trends that are particularly evident in children. If these risk factor trends continue, age-adjusted CVD mortality rates could increase in the coming years.
The Epidemiologic Transition in the United States
The United States, like other high-income countries, has proceeded through four stages of the epidemiologic transition. Recent trends, however, suggest that the rates of decline of some chronic and degenerative diseases have slowed. Because of the large amount of available data, the United States serves as a useful reference point for comparisons.
The Age of Pestilence and Famine (before 1900)
The American colonies were born into pestilence and famine, with half the Pilgrims who arrived in 1620 dying of infection and malnutrition by the following spring. At the end of the 1800s, the U.S. economy was still largely agrarian, with more than 60% of the population living in rural settings. By 1900, average life expectancy had increased to about 50 years. However, tuberculosis, pneumonia, and other infectious diseases still accounted for more deaths than any other cause. CVD accounted for less than 10% of all deaths.
The Age of Receding Pandemics (1900–1930)
By 1900, a public health infrastructure was in place: Forty states had health departments, many larger towns had major public works efforts to improve the water supply and sewage systems, municipal use of chlorine to disinfect water was widespread, pasteurization and other improvements in food handling were introduced, and the educational quality of health care personnel improved. Those changes led to dramatic declines in infectious disease mortality rates. However, the continued shift from a rural, agriculture-based economy to an urban, industrial economy had a number of consequences on risk behaviors and factors for CVD. Owing to a lack of refrigerated transport from farms to urban centers, consumption of fresh fruits and vegetables declined and consumption of meat and grains increased, resulting in diets that were higher in animal fat and processed carbohydrates. In addition, the availability of factory-rolled cigarettes made tobacco more accessible and affordable for the mass population. Age-adjusted CVD mortality rates rose from 300 per 100,000 people in 1900 to approximately 390 per 100,000 during this period, driven by rapidly rising CHD rates.
The Age of Degenerative and Human-Made Diseases (1930–1965)
During this period, deaths from infectious diseases fell to fewer than 50 per 100,000 per year and life expectancy increased to almost 70 years. At the same time, the country became increasingly urbanized and industrialized, precipitating a number of important lifestyle changes. By 1955, 55% of adult men were smoking, and fat consumption accounted for approximately 40% of total calories. Lower activity levels, high-fat diets, and increased smoking pushed CVD death rates to peak levels.
The Age of Delayed Degenerative Diseases (1965–2000)
Substantial declines in age-adjusted CVD mortality rates began in the mid-1960s. In the 1970s and 1980s, age-adjusted CHD mortality rates fell approximately 2% per year and stroke rates fell 3% per year. A main characteristic of this phase is the steadily rising age at which a first CVD event occurs. Two significant advances have been credited with the decline in CVD mortality rates: new therapeutic approaches and the implementation of prevention measures. Treatments once considered advanced, such as angioplasty, bypass surgery, and implantation of defibrillators, are now considered the standard of care. Treatments for hypertension and elevated cholesterol along with the widespread use of aspirin have also contributed significantly to reducing deaths from CVD. In addition, Americans have been exposed to public health campaigns promoting lifestyle modifications effective at reducing the prevalence of smoking, hypertension, and dyslipidemia.
Is the United States Entering the Fifth Age?
The decline in the age-adjusted CVD death rate of 3% per year through the 1970s and 1980s tapered off in the 1990s to 2%. However, CVD death rates declined by 3–5% per year during the first decade of the new millennium. In 2000, the age-adjusted CVD death rate was 341 per 100,000. By 2006, it had fallen to 263 per 100,000. Competing trends appear to be in play. On the one hand, the well-recognized increase in the prevalence of diabetes and obesity, a slowing in the rate of decline of smoking, and a leveling off in the rate of detection and treatment for hypertension are in the negative column. On the other hand, cholesterol levels continue to decline in the face of increased statin use.
Current Worldwide Variations
An epidemiologic transition much like that which occurred in the United States is occurring throughout the world, but unique regional features have modified aspects of the transition in various parts of the world. In terms of economic development, the world can be divided into two broad categories, (1) high-income countries and (2) low- and middle-income countries, which can be further subdivided into six distinct economic/geographic regions. Currently, 85% of the world's population lives in low- and middle-income countries, and it is those countries which are driving the rates of change in the global burden of CVD (Fig. 225-1). Three million CVD deaths occurred in high-income countries in 2001, compared with 13 million in the rest of the world.
CVD data compared with other causes of death. CVD: cardiovascular disease. (Based on data from CD Mathers et al: Deaths and Disease Burden by Cause: Global Burden of Disease Estimates for 2001 byWorld Bank Country Groups. Disease Control Priorities Working Paper 18. April 2004, revised January 2005.)
Approximately 940 million people live in high-income countries, where CHD is the dominant form of CVD, with rates that tend to be twofold to fivefold higher than stroke rates. The rates of CVD in Canada, New Zealand, Australia, and Western Europe tend to be similar to those in the United States; however, among the countries of Western Europe, the absolute rates vary threefold with a clear north/south gradient. The highest CVD death rates are in the northern countries, such as Finland, Ireland, and Scotland, and the lowest rates are in the Mediterranean countries of France, Spain, and Italy. Japan is unique among the high-income countries: stroke rates increased dramatically, but CHD rates did not rise as sharply over the last century. This difference may stem in part from genetic factors, but it is more likely that the fish- and plant-based low-fat diet and resulting low cholesterol levels have played a larger role. Importantly, Japanese dietary habits are undergoing substantial changes, reflected in an increase in cholesterol levels.
Low- and Middle-Income Countries
The World Bank groups the low- and middle-income countries (gross national income per capita less than US $9200) into six geographic regions: East Asia and the Pacific, (Eastern) Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, South Asia, and Sub-Saharan Africa. Although communicable diseases continue to be a major cause of death, CVD has emerged as a significant health concern in low- and middle-income countries. In most, an urban/rural gradient has emerged for CHD, stroke, and hypertension, with higher rates in urban centers.
Although CVD rates are rapidly rising, there are vast differences among the regions and countries and even within individual countries (Fig. 225-2). Many factors contribute to this heterogeneity. First, the regions are in various stages of the epidemiologic transition. Second, vast differences in lifestyle and behavioral risk factors exist. Third, racial and ethnic differences may lead to altered susceptibilities to various forms of CVD. In addition, it should be noted that for most countries in these regions, accurate countrywide data on cause-specific mortality are not complete, as death certificate completion is not routine and most of those countries do not have a centralized registry for deaths.
CVD death as a percentage of total deaths and total population in seven economic regions of the world defined by the World Bank (Based on data from CD Mathers et al: Deaths and Disease Burden by Cause: Global Burden of Disease Estimates for 2001 by World Bank Country Groups. Disease Control Priorities Working Paper 18. April 2004, revised January 2005.)
The East Asia and Pacific region, home to nearly 2 billion people, appears to be straddling the second and third phases of the epidemiologic transition, with China, Indonesia, and Sri Lanka's large combined population driving most of the trends. Overall, CVD is a major cause of death in China, but as in Japan, stroke (particularly hemorrhagic) causes more deaths than does CHD, in a ratio of about 3:1. However, age-adjusted CHD mortality increased 40% from 1984 to 1999, suggesting further epidemiologic transition. China also appears to have a geographic gradient like that of Western Europe, with higher CVD rates in northern China than in southern China by a factor of 6. Other countries, such as Vietnam and Cambodia, are just emerging from the pestilence and famine era.
The Eastern Europe and CentralAsia region is firmly at the peak of the third phase, with the highest death rates (58%) due to CVD in the world, nearly double the rate of high-income countries. More troubling is that nearly 35% of deaths from CHD occur among working-age adults, which is three times the rate in the United States. In Russia, increased CVD rates have contributed to falling life expectancy, particularly for men, whose life expectancy dropped from 71.6 in 1986 to 59 years today. In Poland, by contrast, the age-adjusted mortality rate decreased by approximately 30% for men during the 1990s and slightly more among women. Slovenia, Hungary, the Czech Republic, and Slovakia have had similar declines.
In general, Latin America appears to be in the third phase of the epidemiologic transition, although as in other low- and middle-income regions, there is vast regional heterogeneity, with some areas in the second phase of the transition and some in the fourth. Today, approximately 28% of all deaths in this region are attributable to CVD, with CHD rates (35%) higher than stroke rates (29%). As in Eastern Europe, some countries—Mexico, Costa Rica, and Venezuela—continued an overall increase in age-adjusted CHD mortality of 3%–10% between 1970 and 2002, whereas in others—Argentina, Brazil, Chile, and Columbia—rates appear to have declined by as much as 2% per year over the same period. The Middle East and North Africa region appears to be entering the third phase of the epidemiologic transition, with increasing life expectancy overall and CVD death rates just below those of developed nations. CHD is responsible for 17% of all deaths, and stroke for 7%. The traditional high-fiber diet, low in fat and cholesterol, has changed rapidly. Over the last few decades, daily fat consumption has increased in most of these countries, ranging from a 13.6% increase in Sudan to a 143.3% increase in Saudi Arabia. Over 75% of Egyptians are overweight or obese, and the rate is 67% in Iraq and Jordan. Nearly 60% of Syrians of physical activity and Iraqis report that they are physically inactive (less than 10 min per day).
Most people in South Asia live in rural India, a country that is experiencing an alarming increase in heart disease. CVD accounted for 32% of all deaths in 2000, and an estimated 2 million deaths were expected to occur due to CHD by 2010, representing a 30% increase over the preceding decade. The transition appears to be in the Western style, with CHD as the dominant form of CVD. In 1960, CHD represented 4% of all CVD deaths in India, whereas in 1990 the proportion was >50%. This is somewhat unexpected because stroke tends to be a more dominant factor early in the epidemiologic transition. This finding may reflect inaccuracies in cause-specific mortality estimates or possibly an underlying genetic component. It has been suggested that Indians have exaggerated insulin insensitivity in response to the Western lifestyle pattern that may differentially increase rates of CHD over stroke. The South Asia region has the highest overall prevalence of diabetes in the low-income regions, with rates as high as 14% in urban centers. In certain rural areas, the prevalence of CVD and its risk factors is approaching urban rates. Nonetheless, rheumatic heart disease continues to be a major cause of morbidity and mortality.
For the most part, sub-Saharan Africa remains in the first phase of the epidemiologic transition, with CVD rates half those in developed nations. Life expectancy has decreased by an average of 5 years since the early 1990s largely because of HIV/AIDS and other chronic diseases, according to the World Bank; life expectancies are the lowest in the world. Still, CVD accounts for 46% of noncommunicable deaths and is the leading cause of death among adults >age 35. As more HIV/AIDS patients receive antiretroviral treatment, managing CVD risk factors such as dyslipidemia in this population requires more attention. However, hypertension continues to be the major public health concern and has resulted in stroke being the dominant form of CVD. Rheumatic heart disease is still an important cause of CVD mortality and morbidity.
Global Trends in Cardiovascular Disease
In 1990, CVD accounted for 28% of the world's 50.4 million deaths and 9.7% of the 1.4 billion lost disability-adjusted life years (DALYs), and by 2001, CVD was responsible for 29% of all deaths and 14% of the 1.5 billion lost DALYs. By 2030, when the population is expected to reach 8.2 billion, 33% of all deaths will be the result of CVD (Table 225-2). Of these, 14.9% of deaths in men and 13.1% of deaths in women will be due to CHD. Stroke will be responsible for 10.4% of all male deaths and 11.8% of all female deaths.
Table 225–2. Estimated Morbidity Related to Heart Disease: 2010-2030 |Favorite Table|Download (.pdf)
Table 225–2. Estimated Morbidity Related to Heart Disease: 2010-2030
|Deaths||By 2010||By 2030|
|CVD deaths: annual number of all deaths||18.1 million||24.2 million|
|CVD deaths: percentage of all deaths||30.8%||32.5%|
|CHD deaths: percentage of all male deaths||13.1%||14.9%|
|CHD deaths: percentage of all female deaths||13.6%||13.1%|
|Stroke deaths: percentage of all male deaths||9.2%||10.4%|
|Stroke deaths: percentage of all female deaths||11.5%||11.8%|
In the high-income countries, population growth will be fueled by emigration from the low- and middle-income countries, but the populations of high-income countries will shrink as a proportion of the world's population. The modest decline in CVD death rates that began in the high-income countries in the latter third of the twentieth century will continue, but the rate of decline appears to be slowing. However, these countries are expected to see an increase in the prevalence of CVD, as well as the absolute number of deaths as the population ages.
Significant proportions of the population living in low- and middle-income countries have entered the third phase of the epidemiologic transition, and some are entering the fourth stage. Changing demographics play a significant role in future predictions for CVD throughout the world. For example, between 1990 and 2001, the population of Eastern Europe and Central Asia grew by 1 million people per year, whereas South Asia added 25 million people each year.
CVD rates will also have an economic impact. Even assuming no increase in CVD risk factors, most countries, but especially India and South Africa, will see a large number of people between 35 and 64 die of CVD over the next 30 years as well as an increasing level of morbidity among middle-aged people related to heart disease and stroke. In China, it is estimated that there will be 9 million deaths from CVD in 2030—up from 2.4 million in 2002—with half occurring in individuals between 35 and 64 years old.
Regional Trends in Risk Factors
As indicated earlier, the global variation in CVD rates is related to temporal and regional variations in known risk behaviors and factors. Ecological analyses of major CVD risk factors and mortality demonstrate high correlations between expected and observed mortality rates for the three main risk factors—smoking, serum cholesterol, and hypertension—and suggest that many of the regional variations are based on differences in conventional risk factors.
Every year, more than 5.5 trillion cigarettes are produced, enough to provide every person on the planet with 1,000 cigarettes. Worldwide, 1.3 billion people smoked in 2003, a number that is projected to increase to 1.6 billion by 2030. Tobacco currently causes about 5 million deaths—9% of all deaths—annually. Approximately 1.6 million are CVD-related. If current smoking patterns continue, by 2030 the global burden of disease attributable to tobacco will reach 10 million deaths annually. A unique feature of the low- and middle-income countries is easy access to smoking during the early stages of the epidemiologic transition due to the availability of relatively inexpensive tobacco products. In South Asia, the prominence of locally produced forms of tobacco other than manufactured cigarettes makes control of consumption more challenging.
Total caloric intake per capita increases as countries develop. With regard to cardiovascular disease, a key element of dietary change is an increase in intake of saturated animal fats and hydrogenated vegetable fats, which contain atherogenic trans-fatty acids, along with a decrease in intake of plant-based foods and an increase in simple carbohydrates. Fat contributes less than 20% of calories in rural China and India, less than 30% in Japan, and well above 30% in the United States. Caloric contributions from fat appear to be falling in the high-income countries. In the United States, between 1971 and 2000, the percentage of calories derived from saturated fat decreased from 13% to 11%.
The increased mechanization that accompanies the economic transition leads to a shift from physically demanding agriculture-based work to largely sedentary industry- and office-based work. In the United States, approximately one-quarter of the population does not participate in any leisure-time physical activity and only 22% report engaging in sustained physical activity for at least 30 minutes on 5 or more days per week (the current recommendation). In contrast, in countries such as China, physical activity is still integral to everyday life. Approximately 90% of the urban population walks or rides a bicycle to work, shopping, or school daily.
Worldwide, high cholesterol levels are estimated to cause 56% of ischemic heart disease and 18% of strokes, amounting to 4.4 million deaths annually. As countries move through the epidemiologic transition, mean population plasma cholesterol levels tend to rise. Social and individual changes that accompany urbanization clearly play a role because plasma cholesterol levels tend to be higher among urban residents than among rural residents. This shift is driven largely by greater consumption of dietary fats—primarily from animal products and processed vegetable oils—and decreased physical activity. In the high-income countries, in general, mean population cholesterol levels are falling, whereas wide variation is seen in the low- and middle-income countries.
Elevated blood pressure is an early indicator of the epidemiologic transition. Worldwide, approximately 62% of strokes and 49% of cases of ischemic heart disease are attributable to suboptimal (>115 mmHg systolic) blood pressure, which is believed to account for more than 7 million deaths annually. Remarkably, nearly half of this burden occurs among those with systolic blood pressure <140 mmHg, even as this level is used at the arbitrary threshold for defining hypertension in many national guidelines. Rising mean population blood pressure is apparent as populations industrialize and move from rural to urban settings. Among urban-dwelling men and women in India, for example, the prevalence of hypertension is 25.5% and 29.0%, respectively, whereas it is 14.0% and 10.8%, respectively, in rural communities. One major concern in low- and middle-income countries is the high rate of undetected, and therefore untreated, hypertension. This may explain, at least in part, the higher stroke rates in these countries in relation to CHD rates during the early stages of the transition. The high rates of hypertension, especially undiagnosed hypertension, throughout Asia probably contribute to the high prevalence of hemorrhagic stroke in the region.
Although clearly associated with increased risk of CHD, much of the risk posed by obesity may be mediated by other CVD risk factors, including hypertension, diabetes mellitus, and lipid profile imbalances. In the mid-1980s, the World Health Organization's MONICA Project sampled 48 populations for cardiovascular risk factors. In all but one male population (China) and in most of the female populations, between 50% and 75% of adults age 35–64 years were overweight or obese. In addition, the prevalence of extreme obesity (BMI >40 kg/m2) more than tripled, increasing from 1.3% to 4.9%. In many of the low- and middle-income countries, obesity appears to coexist with undernutrition and malnutrition. Obesity is increasing throughout the world, particularly in developing countries, where the trajectories are steeper than those experienced in the developed countries. According to the latest World Health Organization (WHO) data, this is equivalent to about 1.3 billion overweight adults in the world. A survey undertaken in 1998 found that as many as 58% of African women living in South Africa might have been overweight or obese.
As a consequence of, or in addition to, increasing body mass index and decreasing levels of physical activity, worldwide rates of diabetes—predominantly Type 2 diabetes—are on the rise. In 2003, 194 million adults, or 5% of the world's population, had diabetes. By 2025, this number is predicted to increase 72 percent to 333 million. By 2025, the number of people with Type 2 diabetes is projected to double in three of the six low- and middle-income regions: Middle East and North Africa, South Asia, and Sub-Saharan Africa. There appear to be clear genetic susceptibilities to diabetes mellitus in various racial and ethnic groups. For example, migration studies suggest that South Asians and Indians tend to be at higher risk than are people of European ancestry.
Although CVD rates are declining in the high-income countries, they are increasing in virtually every other region of the world. The consequences of this preventable epidemic will be substantial on many levels: individual mortality and morbidity rates, family suffering, and staggering economic costs.
Three complementary strategies can be used to lessen the impact. First, the overall burden of CVD risk factors can be lowered through populationwide public health measures such as national campaigns against cigarette smoking, unhealthy diets, and physical inactivity. Second, it is important to identify higher-risk subgroups of the population that stand to benefit the most from specific, low-cost prevention interventions, including screening for and treatment of hypertension and elevated cholesterol. Simple, low-cost interventions, such as the "polypill," a regimen of aspirin, a statin, and an anithypertensive agent, also need to be explored. Third, resources should be allocated to acute as well as secondary prevention interventions. For countries with limited resources, a critical first step in developing a comprehensive plan is better assessment of cause-specific mortality and morbidity, as well as the prevalence of the major preventable risk factors.
In the meantime, the high-income countries must continue to bear the burden of research and development aimed at prevention and treatment, being mindful of the economic limitations of many countries. The concept of the epidemiologic transition provides insight into methods to alter the course of the CVD epidemic. The efficient transfer of low-cost preventive and therapeutic strategies could alter the natural course of this epidemic and thereby reduce the excess global burden of preventable CVD.