Chapter 1: General Principles

1.1: Global Burden of Cardiovascular Disease

Thomas A. Gaziano, MD, MSc This author has nothing to disclose.
Learner Objectives Upon completion of this module, the reader will be able to: 1. Evaluate the relationship between income and stage in epidemiologic transition in order to prepare for clinical settings in different areas of the world and use resources in an effective manner. 2. Identify risk factors and be familiar with prevalence data to be aware of patients at risk for cardiovascular disease (CVD). 3. Prescribe a combination of therapeutics in secondary prevention. 4. Assess cost-effectiveness of incremental strategies for treatment of myocardial infarction (MI) or stroke in low- and middleincome settings in treatment protocols. 5. Analyze risk factors and effectively employ use of risk scores.

Shifting Burden
Over the last decade, CVD has become the single largest cause of death worldwide. In 2004, CVD caused an estimated 17 million deaths and led to 151 million disability-adjusted life-years (DALYs) lost. In 2001, three-fourths of global deaths and 82% of total DALYs lost due to coronary heart disease (CHD) occurred in low- and middle-income countries.1 Today, CVD accounts for approximately 30% of deaths worldwide, including nearly 40% in high-income countries and about 28% in low- and middle-income countries, and 39% of noncommunicable disease deaths globally (Figure 1).

Proportion of Noncommunicable Disease Deaths Among Those Under 70 Years

27% 4%

39%

Epidemiologic Transitions
The overall increase in the global burden of CVD and the distinct mortality patterns in the various regions (Table 1) result in part from the epidemiologic transition, which includes four basic stages, as follows: 1. 2. 3. 4. Pestilence and famine, Receding pandemics, Degenerative and man-made diseases, and Delayed degenerative diseases.

Cancers Cardiovascular disease Chronic respiratory diseases

Diabetes Digestive diseases Other noncommunicable diseases

Figure 1 Proportion of Noncommunicable Disease Deaths Among Those Under 70 Years

Reproduced with permission from World Health Organization. Global Status Report on Noncommunicable Diseases 2010. Geneva: World Health Organization.

Movement through these stages has dramatically shifted the causes of death over the last two centuries, from infectious diseases and malnutrition in the first stage, to CVD and cancer in the third and fourth stages. Although the transition through the age of pestilence and famine has occurred much later in the low- and middle-income countries, it has also occurred more rapidly, driven largely by the transfer of low-cost agricultural technologies and public health advances. A fifth stage, characterized by an epidemic of inactivity and obesity, may be emerging in some countries.

The first stage, pestilence and famine, is characterized by the predominance of malnutrition and infectious disease and by the infrequency of CVD as a cause of death. Tuberculosis, dysentery, cholera, and influenza are often fatal, resulting in a mean life expectancy of about 30 years. CVD, which accounts for <10% of deaths, takes the form of rheumatic heart disease and other cardiomyopathies due to infection and malnutrition. Approximately 10% of the worlds population remains in the age of pestilence and famine, particularly Sub-Saharan Africa.

1.1: Global Burden of Cardiovascular Disease

1.1.1

Stages of the Epidemiological Transition and Its Global Status, by Region

Stage Description Life Expectancy (years) Dominant Form of CVD Percentage of Deaths Due to CVD Percentage of the Worlds Population in This Stage 11% Regions Affected

Pestilence and famine

Predominance of malnutrition and infectious diseases

35

Rheumatic heart disease, cardiomyopathy due to infection and malnutrition Rheumatic valvular disease, ischemic heart disease (IHD), hemorrhagic stroke

<10%

Sub-Saharan Africa, parts of all regions excluding highincome regions

Receding pandemics

Improved nutrition and public health leads to increase in chronic diseases, hypertension

50

10-35%

38%

South Asia, southern East Asia and the Paci c, parts of Latin America, and the Caribbean Europe and Central Asia, northern East Asia and the Paci c, Latin America and the Caribbean, Middle East and North Africa, and urban parts of most low income regions (especially India) High-income countries, parts of Latin America and the Caribbean

Degenerative and man-made diseases

Increased fat and caloric intake, widespread tobacco use, chronic disease deaths exceed mortality from infections and malnutrition

60

IHD, stroke (ischemic and hemorrhagic)

35-65%

35%

1
Delayed degenerative diseases CVD and cancer are leading causes of morbidity and mortality, prevention and treatment avoids death and delays onset; age-adjusted CVD declines >70 IHD, stroke (ischemic and hemorrhagic), congestive heart failure 40-50% 15%

Table 1 Stages of the Epidemiological Transition and Its Global Status, by Region
CVD = cardiovascular disease. Reproduced with permission from Gaziano TA, Gaziano JM. Global burden of cardiovascular disease. In: Bonow RO, Mann DL, Zipes DP, Libby P. Braunwalds Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia: Saunders; 2011.

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. The change most characteristic of this phase is a precipitous decline in infant and child mortality accompanied by a substantial increase in life expectancy. Deaths due to CVD (rheumatic valvular disease, hypertension, and stroke) increase to between 10% and 35% of all deaths. Almost 40% of the worlds population is currently in this stage. The age of degenerative and man-made diseases is distinguished by mortality from noncommunicable diseasesprimarily CVDsurpassing mortality from malnutrition and infectious diseases. Caloric intake, particularly from animal fat, increases. CHD and stroke are prevalent, and between 35% and 65% of all deaths can be traced to CVD. Typically, the rate of CHD
1.1.2 Chapter 1: General Principles

deaths exceeds that of stroke by a ratio of 2:1 to 3:1. During this period, average life expectancy surpasses age 50. Roughly 35% of the worlds 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, reductions in risk behaviors and factors such as smoking cessation programs and effective blood pressure control make even greater contributions to the decline in age-adjusted rates of death. Further, these reductions are aided by improvements in acute hospital management and technological advances, such as the availability of bypass surgery. CHD, stroke, and congestive heart failure are the primary forms of CVD. About 15% of the worlds 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.

Major Causes of Death in Persons of All Ages for Low- and Middle-Income Regions
60 50

Percent of Total Deaths

40

30

Figure 2 Major Causes of Death in Persons of All Ages for Low- and MiddleIncome Regions
Reproduced with permission from Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ, eds. Global Burden of Disease and Risk Factors. New York: The World Bank and Oxford University Press; 2006.

20

10

Europe & Central Asia

Middle East & North Africa

South Asia

East Asia & Pacic

Malignant Neoplasms Chronic Lung Diseases

Latin America & Caribbean

Injuries HIV/AIDS

Sub-Saharan Africa

Cardiovascular Diseases Respiratory Infections

1
Troubling trends in certain risk behaviors and risk factors may foreshadow a new phase of the epidemiologic transition, the age of inactivity and obesity.2 In the industrialized world, physical activity continues to decline while total caloric intake increases. Rates of type 2 diabetes mellitus, hypertension, and lipid abnormalities are on the rise, trends that are particularly evident in children. If these trends continue, age-adjusted CVD mortality rates, which have declined over the past several decades in developed countries, could level or even increase in the coming years. are in the northern countries, such as Finland, Ireland, and Scotland, with the lowest CVD rates 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.

Current Worldwide Variations in Burden of Cardiovascular Disease

An epidemiologic transition much like the one that occurred in the developed countries is occurring throughout the world, but unique regional features have modified aspects of the transition in various parts of the world. The rate of transition varies widely, leading to large discrepancies in disease burden. 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 worlds population lives in low- and middle-income countries, and it is these countries that are driving the rates of change in the global burden of CVD.

Low- and Middle-Income Countries

The World Bank groups the low- and middle-income countries (gross national income per capita less than US $12,195) into six geographic regions, as follows: 1. 2. 3. 4. 5. 6. 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.

High-Income Countries
Nearly 1 billion people live in the high-income countries, where CHD is the dominant form of CVD, with rates that tend to be two- to five-fold 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 three-fold, with a clear north/south gradient. The highest CVD death rates

Although communicable diseases continue to be a major cause of death, CVD has emerged as a significant health concern in the low- and middle-income countries. In most, an urban/rural gradient has emerged for CHD, stroke, and hypertension, with higher rates in urban centers.

1.1: Global Burden of Cardiovascular Disease

1.1.3

While CVD rates are rapidly rising, vast differences exist among the regions (Figure 2) and countries, and even within the countries themselves. Many factors contribute to this heterogeneity. First, the regions are in various stages of the epidemiological 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 country-wide data on cause-specific mortality are not complete, as death certificate completion is not routine, and most countries do not have a centralized registry for deaths. East Asia and Pacific Region The East Asia and Pacific region, home to nearly 2 billion people, appears to be straddling the second and third phases of the epidemiological transition, with China, Indonesia, and Sri Lankas large combined population driving most of the trends. Overall, CVD is a major cause of death in China, but, like Japan, stroke (particularly hemorrhagic) causes more deaths than CHD, in a ratio of about 3:1. However, age-adjusted CHD mortality increased 40% from 1984 to 1999, suggesting further epidemiologic transition.

Middle East and North Africa The Middle East and North Africa region appears to be entering the third phase of the epidemiological transition, with increasing life expectancy overall and CVD death rates just below 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 past 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 and Iraqis report that they are physically inactive (<10 minutes per day). South Asia 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 will 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 epidemiological 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 lowincome regions, with rates as high as 14% in urban centers. In certain rural areas, the prevalence of CVD and its risk factors are approaching urban rates. Nonetheless, rheumatic heart disease continues to be a major cause of morbidity and mortality. Sub-Saharan Africa For the most part, Sub-Saharan Africa remains in the first phase of the epidemiological transition with CVD rates one-quarter of those in developed nations. This area remains the only region where CVD is not the leading cause of death. Life expectancy has decreased by an average of 5 years since the early 1990s, largely because of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (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 over the age of 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 a prominent challenge.

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 six. Other countries, such as Vietnam and Cambodia, are just emerging from the pestilence and famine transition. Eastern Europe and Central Asia The Eastern Europe and Central Asia region is firmly in the peak of the third phase, with the highest death rates (58%) due to CVD in the world, nearly double the rate of some high-income countries. More troubling is that nearly 35% of the deaths from CHD occur among working-age adults, which is three times the rate of the United States. In Russia, increased CVD rates have contributed to falling life expectancy, particularly for men, whose life expectancy has dropped from age 71.6 years 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. Latin America and the Caribbean In general, Latin America appears to be in the third phase of the epidemiological 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 higher than stroke rates. Like Eastern Europe, some countriesMexico, Costa Rica, and Venezuelacontinued an overall increase in age-adjusted CHD mortality of 310% between 1970 and 2002, while in others-Argentina, Brazil, Chile, and Columbia-rates appear to have declined by as much as 2% per year over the same time period.

1.1.4

Chapter 1: General Principles

Global Trends in Cardiovascular Disease

In 1990, CVD accounted for 28% of the worlds 50.4 million deaths and 9.7% of the 1.4 billion lost 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. 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. 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 worlds population. The modest decline in CVD death rates that began in the high-income countries in the latter third of the 20th 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 portions of the population living in low- and middleincome countries have entered the third phase of the epidemiological 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 the ages of 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 2030up from 2.4 million in 2002with one-half occurring in individuals between 35 and 64 years old.

<145 mm Hg, even as this level is used at the arbitrary threshold for defining hypertension in many national guidelines.3 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 likely contribute to the high prevalence of hemorrhagic stroke in the region.

Tobacco
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 deaths9% of all deathsannually. 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 epidemiological transition due to the availability of relatively inexpensive tobacco products. In South Asia, the prominence of other locally produced forms of tobacco besides manufactured cigarettes makes control of consumption more challenging.

Lipids
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 epidemiological 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 largely driven by greater consumption of dietary fatsprimarily from animal products and processed vegetable oilsand decreased physical activity. In the highincome countries, in general, mean population cholesterol levels are falling, while wide variation is seen in the low- and middleincome countries. Physical Inactivity 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
1.1: Global Burden of Cardiovascular Disease 1.1.5

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 factorssmoking, serum cholesterol, and hypertensionand suggest that many of the regional variations are based on differences in conventional risk factors.

Hypertension
Elevated blood pressure is an early indicator of the epidemiological transition. Worldwide, approximately 54% of strokes and 47% of cases of ischemic heart disease are attributable to suboptimal (>115 mm Hg systolic) blood pressure, which is believed to account for more than 7 million deaths annually. Remarkably, nearly onehalf of this burden occurs among those with systolic blood pressure

Ischemic Heart Disease and Stroke Mortality Versus BMI in the Range 15-50 kg/m2
(excluding the rst 5 years of follow-up)
8.3 7.8

8
5.8

6.6 126 286 646 2.9 2.6 96

Ischemic Heart Disease

Yearly Deaths per 1,000 (95% CI)

5.1 1626 4.1

4
3.0 2.6 675 2.7 2289 4497

3.5 4929

3074

2.2 2.0 1.7 220 100 37 46

Stroke

2
1.3 1.2 1.2 1.2 837

1.3

504

417

1 0.5

1040 1507 1420

0 15

20

25

30

35

40

50

Baseline BMI (kg/m2) Number at Risk

64652 247268 92895 41714 16726 7562 3664 3278 179450 195615

Figure 3 Ischemic Heart Disease and Stroke Mortality Versus BMI in the Range 15-50 kg/m2 (excluding the first 5 years of follow-up)
Relative risks at ages 3589 years, adjusted for age at risk, sex, smoking, and study, were multiplied by a common factor (i.e., floated) to make the weighted average match the Prospective Studies Collaboration mortality rate at ages 3579 years. Floated mortality rates shown above each square and numbers of deaths below. Area of square is inversely proportional to the variance of the log risk. Boundaries of body mass index (BMI) groups are indicated by tick marks. 95% confidence intervals (CIs) for floated rates reflect uncertainty in the log risk for each single rate. Reproduced with permission from Whitlock G, Lewington S, Sherliker P, et al., on behalf of the Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96.

current recommendation). In contrast, in countries like 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.

bilities to diabetes mellitus of various racial and ethnic groups. For example, migration studies suggest that South Asians and Indians tend to be at higher risk than those of European extraction.

Diabetes
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 worlds population, had diabetes. By 2025, this number is predicted to increase 72% to 333 million. By 2025, the number of people with type 2 diabetes is projected to double in three of the six low- and middleincome regions: Middle East and North Africa, South Asia, and Sub-Saharan Africa. There appear to be clear genetic suscepti1.1.6 Chapter 1: General Principles

Obesity
Although clearly associated with increased risk of CVD (Figures 3, 4a, b),4 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 Organizations (WHOs) MONICA Project sampled 48 populations for CV risk factors. In all but one male population (China), and in most of the female populations, between 50% and 75% of adults ages 35-64 years were overweight or obese.

Vascular Risk Factors Versus BMI at Baseline in the Range 15-50 kg/m2 (1 of 2)
A
Blood Pressure
160
151.9

B
Cholesterol Concentration (mmol/L), or Ratio of Cholesterol Fractions
Systolic
141.4 146.2

Blood Cholesterol Fractions

160
4.83 4.71 4.56 4.44 4.39

Non-HDL Cholesterol Ratio of Mean Non-HDL Cholesterol to Mean HDL Cholesterol

4.06

4.30

140
130.1 136.5

140
3.59 3.54 3.94

Blood Pressure (mm Hg)

123.9 125.7

3.46 2.92 3.28

120

122.6

120
2.30

2.35

100
94.4 88.4 89.3

100

2.05 1.75

1.68 1.39 1.39 1.28

Diastolic

1.54

1
HDL Cholesterol

80

78.9 74.9 75.0 76.7

83.8

80

1.12

1.07

Males Females

0 15

25 35 Baseline BMI (kg/m2)

50

0 15

25 35 Baseline BMI (kg/m2)

50

Figure 4a Vascular Risk Factors Versus BMI at Baseline in the Range 1550 kg/m2 (1 of 2)
Adjusted for baseline age, baseline smoking status (apart from the smoking findings), and study. Numerical values are shown for 2022.5 kg/m2, for 3032.5 kg/m2, and for the extreme body mass index (BMI) groups. Boundaries of BMI groups are indicated by tick marks. 95% confidence intervals (CIs) are not shown, but most are narrower than the heights of the plotted symbols. (A) Blood pressure (in 533,242 males and 348,790 females). (B)  Blood cholesterol fractions (in 62,364 males and 52,575 females with total and high-density lipoprotein (HDL) cholesterol both measured); dashed line indicates the ratio of mean non-HDL cholesterol to mean HDL cholesterol (mean of the individual ratios would be about 812% greater). Reproduced with permission from Whitlock G, Lewington S, Sherliker P, et al., on behalf of the Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96.

In addition, the prevalence of extreme obesity (body mass index [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 by the developed countries. According to the latest 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 may be overweight or obese.

Diet
Total caloric intake per capita increases as countries develop. With regard to CVD, 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 <20% of calories in rural China and India, <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
1.1: Global Burden of Cardiovascular Disease 1.1.7

Vascular Risk Factors Versus BMI at Baseline in the Range 15-50 kg/m2 (2 of 2)
C
80

Prevalence in Males
73.2 69.2 71.7 66.5

D
Drinking

80

Prevalence in Females

61.6

60

59.3

60 Females (%)

56.9

Males (%)

48.2

46.4 40.4 37.0 31.0

40
32.8 32.9

Smoking

40

Drinking

21.1

20
11.4 5.8 2.82.9

20
Diabetes
1.8 1.8

17.6 10.3 5.8

Smoking Diabetes Males Females

0 15

25 35 Baseline BMI (kg/m2)

50

0 15

25 35 Baseline BMI (kg/m2)

50

Figure 4b Vascular Risk Factors Versus BMI at Baseline in the Range 1550 kg/m2 (2 of 2)
Adjusted for baseline age, baseline smoking status (apart from the smoking findings), and study. Numerical values are shown for 2022.5 kg/m2, for 3032.5 kg/m2, and for the extreme body mass index (BMI) groups. Boundaries of BMI groups are indicated by tick marks. 95% confidence intervals (CIs) are not shown, but most are narrower than the heights of the plotted symbols. (C) Prevalence in males for alcohol drinking (168,283), cigarette smoking (334,496), and diabetes (378,854). (D) Prevalences in females for alcohol drinking (129,301), cigarette smoking (226,307), and diabetes (319,401). Reproduced with permission from Whitlock G, Lewington S, Sherliker P, et al., on behalf of the Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96.

percentage of calories derived from saturated fat decreased from 13% to 11%.

Scope of Interventions
The large reductions in age-adjusted CVD mortality rates that have occurred in high-income countries result from three complementary types of interventions. One strategy targets those with acute or established CVD. A second entails risk assessment and targeting those at high risk due to multiple risk factors for intervention before their first CVD event. The third strategy uses mass education or policy interventions directed at the entire population to reduce the overall level of risk factors. This section highlights the variety of cost-effective interven1.1.8 Chapter 1: General Principles

tions. Much work remains undone in developing countries to determine the best strategies given limited resources, but if implemented, these interventions could go a long way toward reducing the burden.Table 2 lists the cost-effectiveness ratios for many of the high-yield interventions that could be or have been adopted in developing regions. Those at highest risk are those suffering an MI or stroke; as many as one-half die before they ever receive medical attention. For those who do make it to a hospital, standard medical therapies were examined in a cost-effectiveness analysis.5 Four incremental strategies were evaluated for the treatment of MI and compared to a strategy of no treatment as a base case for the six World Bank low- and middle-income regions. The four strategies compared were: 1) aspirin; 2) aspirin and atenolol; 3)

Cost-Effectiveness for a Selection of CHD Interventions in Developing Regions

Cost-Effectiveness Ratio ($US/DALY)* Drug Treatments
Acute Myocardial Infarction ASA, BB ASA, BB, SK ASA, BB,TPA Secondary Treatment (CHD) Multidrug regimen (ASA, BB, ACEI, statin) Coronary artery bypass grafting (CABG) Primary prevention (multidrug regimen) $300$400 $24,040$72,345 $700$1,200 $11$22 $634$734 $15,860$18,893

Table 2 Cost-Effectiveness for a Selection of CHD Interventions in Developing Regions

ASA = aspirin; BB = beta-blocker; SK = streptokinase; ACEI = angiotensin-converting enzyme inhibitor; tPA = tissue plasminogen activator. *Across six World Bank regions. CHD = coronary heart disease. Range includes different estimates of cost of interventions, as well as blood pressure reduction (<$0.50$1.00). Range includes estimates of cost of interventions (<$0.50$6.00). References 1. Gaziano TA. Cardiovascular disease in the developing world and its cost-effective management. Circulation 2005;112:3547-53. 2. Gaziano TA, Galea G, Reddy KS. Scaling up interventions for chronic disease prevention: the evidence. Lancet 2007;370:1939-46. 3. Gaziano TA, Opie LH, Weinstein MC. Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis. Lancet 2006;368:679-86.

Policy Interventions
Tobacco Price increase of 33% Nonpolicy interventions Salt Reduction 28 mmHg reduction Fat-related interventions Reduced saturated fat intake Trans fat replacement, 7% reduction in CHD Cost saving $2,900 $50$1,500 Cost saving $250 $2$85 $33$1,432

aspirin, atenolol, and streptokinase; and 4) aspirin, atenolol, and tissue plasminogen activator (t-PA). The incremental cost per Quality of Adjusted Life Years (QALY) gained for both the aspirin and beta-blocker interventions was under $25 for all six regions. Costs per QALY gained for streptokinase were between $630 and $730 across the regions. Incremental cost-effectiveness ratios for t-PA were around $16,000/ QALY gained, compared with streptokinase. Minor variations occurred between regions due to small differences in follow-up care based on regional costs. Secondary prevention strategies are equally cost-effective in developing countries. Studies show that a combination of aspirin, an angiotensin-converting enzyme inhibitor, a beta-blocker, and a statin for secondary prevention can lead to acceptable costeffectiveness ratios in all developing regions.5 Use of currently available generic agents, even in the absence of the so-called polypill, could be highly cost-effective, on the order of $300$400 per person per QALY gained.6 Primary prevention is paramount for the large number of individuals who are at high risk for CVD. Given limited resources, finding low-cost prevention strategies is a top priority. Using prediction rules or risk scores to identify those at higher risk in order to target specific behavioral or drug interventions is a well-established primary prevention strategy and has proven to be cost-effective in developing countries.6, 7 Most have included

age, sex, hypertension, smoking status, diabetes mellitus, and lipid values, while others have also included family history.8, 9 Recently, many investigators have examined whether additional laboratory-based risk factors can add to predictive discrimination of the risk factors used in the Framingham Heart Study risk score (Figures 5a, b). The recent analyses in theARIC (Atherosclerosis Risk in Communities) study,10 and the Framingham Offspring Study,11, 12 suggested that little additional information was gained when other blood-based novel risk factors were added to the traditional risk factors. Although the Reynolds Risk Score for women,13 which added family history, high-sensitivity C-reactive protein (hs-CRP), and glycated hemoglobin levels, only had a marginally higher C-statistic (0.808) than the Framingham covariates (0.791), it correctly reclassified many individuals at intermediate risk (Figure 6). Some women deemed low risk by the Framingham risk score were reclassified as intermediate or high risk according to the Reynolds Risk Score and, thus, would have been eligible for more aggressive management. Also, some women who were initially high risk according to Framingham were reclassified as lower risk and, thus, would not have needed treatment. More attention is now focused on developing risk scores that would be easier to use in clinical practice without loss of predictive discrimination in resource-poor countries. In high-income countries, a prediction rule that requires a lab test is an incon1.1: Global Burden of Cardiovascular Disease 1.1.9

Step 1
Years 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74

Assessing 10-Year Coronary Heart Disease Risk in Men (1 of 2)

Step 4 Step 8
Age LDL Pts -1 0 1 2 3 4 5 6 7 Chol Pts [-1] [0] [1] [2] [3] [4] [5] [6] [7] Systolic (mm HG) <120 120-129 130-139 140-159 160 <80 0 [0]pts 0[0] pts 1[1] pts 2[2] pts 3[3] pts Blood Pressure Diastolic (mm Hg) 80-84 85-89 90-99 100 LDL Pts Total <-3 -2 -1 0 1 2 3 4 Smoker Chol Pts [0] [2] No Yes LDL Pts 0 2 Chol Pts [0] [2] 5 6 7 8 9 10 11 12 13 14 1% 2% 2% 3% 4% 4% 6% 7% 9% 11% 14% 18% 22% 27% 33% 40% 47% 56%

(determine CHD risk from point total)

CHD Risk Chol Pts 10 Yr Total CHD Risk

10 Yr CHD Risk

[<-1] [0] [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]

[2%] [3%] [3%] [4%] [5%] [7%] [8%] [10%] [13%] [16%] [20%] [25%] [31%] [37%] [45%] [53%]

Note: When systolic and diastolic pressures provide different estimates for point scores, use the higher number

Step 5
Diabetes LDL Pts

Step 6

Step 2
LDL - C (mg/dl) <100 100-129 130-159 160-190 190 (mmol/L) <2.59 2.60-3.36 3.37-4.14 4.15-4.92 4.92 Cholesterol (mg/dl) <160 160-199 200-239 (mmol/L) <4.14 4.15-5.17 5.18-6.21 6.22-7.24 7.25 Chol Pts [-3] [0] [1] [2] [3] LDL Pts -3 0 0 1 2 Age No Yes

0 2

Step 7

(sum from steps 1 - 6)

Adding up the Points

LDL-C or Chol HDL - C Blood Pressure Diabetes Smoker Point Tool

Step 9
Age (years) 30-34 35-39
* Hard CHD events exclude angina pectoris ** Low risk was calculated for a person the same age, optimal blood pressure, LDL-C 100-129 mg/dL or cholesterol 160-199 mg/dl, HDL-C 45 mg/dL for men or 55 mg/dL for women non-smoker, no diabetes Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian
population in Massachusetts, USA

(compare to average person your age)

Comparative Risk Average 10 Average 10 Yr Yr CHD Risk Hard* CHD Risk 3% 5% 7% 11% 14% 16% 21% 25% 30% 1% 4% 4% 8% 10% 13% 20% 22% 25% Low** 10 Yr CHD Risk 2% 3% 4% 4% 6% 7% 9% 11% 14%

240-279 280

Step 3
HDL - C (mg/dl) <35 35-44 45-49 50-59 60 (mmol/L) <0.90 0.91-1.16 1.17-1.29 1.30-1.55 1.56 LDL Pts 2 1 0 0 -1 Chol Pts [2] [1] [0] [0] [-2]

40-44 45-49 50-54 55-59 60-64 65-69 70-74

Key
Color green white yellow rose red Relative Risk Very low Low Moderate High Very high

Figure 5a Assessing 10-Year Coronary Heart Disease Risk in Men (1 of 2)

Adapted with permission from Wilson PW, DAgostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

venience; in low-income countries, with limited testing facilities, it may be too expensive for widespread screening or preclude its use altogether. In response to this real concern, the WHO recently released risk-prediction charts for the different regions of the world with and without cholesterol.14, 15 A study based on the US National Health and Nutrition Examination Survey (NHANES) follow-up cohort demonstrated that a non-lab-based risk tool that uses information obtained in a single encounter (age, systolic blood pressure, BMI, diabetes status, and smoking status) can predict CVD outcomes as well as one that requires lab testing with C-statistics of 0.79 for men and 0.83 for women that were no different from the Framinghambased risk tool.16 The association between BMI and cholesterol has been confirmed by large cohorts.4 Further, the results of the goodness-of-fit tests suggest that the non-laboratory-based model is well-calibrated across a wide range of absolute risk levels and without changes in classifica1.1.10 Chapter 1: General Principles

tion of risk. A risk score based on the US NHANES follow-up cohort can be used to predict CVD events in regions where cholesterol testing is not available (Figures 7a, b). Education and public policy interventions that have reduced smoking rates, lowered mean blood pressure levels, and improved lipid profiles have contributed to the reduction in CHD rates.17 Education and policy efforts directed at tobacco consumption have contributed substantially to the reductions in CVD. In addition, salt and cholesterol reduction has been evaluated as a cost-effective strategy to reduce stroke and MI in lowand middle-income countries by investigators at the WHO.18 Community interventions have reduced levels of multiple risk factors and, in some cases, CHD mortality.

Tobacco
Tobacco control can be conceptualized in terms of strategies that reduce the supply of, or demand for, tobacco. Most public health and clinical strategies to date focus on reducing demand

Step 1

Assessing 10-Year Coronary Heart Disease Risk in Women (2 of 2)

Step 4 Step 8
Age Blood Pressure Chol Pts [-9] [-4] [0] [3] [6] [7] [8] [8] [8] Systolic (mm HG) <120 120-129 130-139 140-159 160 <80 -3 [-3]pts 0[0] pts 0[0] pts 2[2] pts 3[3] pts Diastolic (mm Hg) 80-84 85-89 90-99 100
LDL Pts Total -2 -1 0 1 2 3 4 5 6 7

(determine CHD risk from point total)

Years 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74

LDL Pts --9 -4 0 3 6 7 8 8 8

CHD Risk Chol Pts 10 Yr Total CHD Risk 1% 2% 2% 2% 3% 3% 4% 5% 6% 7% 8% 9% 11% 13% 15% 17% 20% 24% 27% 32% [-2] [-1] [0] [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]

10 Yr CHD Risk [1%] [2%] [2%] [2%] [3%] [3%] [4%] [4%] [5%] [6%] [7%] [8%] [10%] [11%] [13%] [15%] [18%] [20%] [24%] [27]

Note: When systolic and diastolic pressures provide different estimates for point scores, use the higher number

Step 5
Diabetes LDL Pts Chol Pts [0] [4]

Step 6
Smoker LDL Pts No Yes 0 2 Chol Pts [0] [2]

Step 2
LDL - C (mg/dl) <100 100-129 130-159 160-190 190 (mmol/L) <2.59 2.60-3.36 3.37-4.14 4.15-4.92 4.92 Cholesterol (mg/dl) <160 160-199 200-239 240-279 280 (mmol/L) <4.14 4.15-5.17 5.18-6.21 6.22-7.24 7.25 Chol Pts [-2] [0] [1] [1] [3] LDL Pts -2 0 0 2 2 Age No Yes

8 9 10 11 12 13 14 15 16 17

0 4

Step 7

(sum from steps 1 - 6)

Adding up the Points

LDL-C or Chol HDL - C Blood Pressure Diabetes Smoker Point Tool

Step 9
Age (years) 30-34 35-39
* Hard CHD events exclude angina pectoris ** Low risk was calculated for a person the same age, optimal blood pressure, LDL-C 100-129 mg/dL or cholesterol 160-199 mg/dl, HDL-C 45 mg/dL for men or 55 mg/dL for women non-smoker, no diabetes Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian
population in Massachusetts, USA

(compare to average person your age)

Comparative Risk Average 10 Average 10 Yr Yr CHD Risk Hard* CHD Risk <1% <1% 2% 5% 8% 12% 12% 13% 14% <1% <1% 1% 2% 3% 7% 8% 8% 11% Low** 10 Yr CHD Risk <1% 1% 2% 3% 5% 7% 8% 8% 8%

Step 3
HDL - C (mg/dl) <35 35-44 45-49 50-59 60 (mmol/L) <0.90 0.91-1.16 1.17-1.29 1.30-1.55 1.56 LDL Pts 5 2 1 0 -2 Chol Pts [5] [2] [1] [0] [-3]

40-44 45-49 50-54 55-59 60-64 65-69 70-74

Key
Color green white yellow rose red Relative Risk Very low Low Moderate High Very high

Figure 5b Assessing 10-Year Coronary Heart Disease Risk in Women (2 of 2)

Adapted with permission from Wilson PW, DAgostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

through economic disincentives (taxes), health promotion (media and packaging efforts), restricted access (to advertising and tobacco), or clinical assistance for cessation. The WHO effort to catalyze the creation of a global treaty against tobacco use was a key milestone. In May 2003, the WHO World Health Assembly unanimously adopted the WHO Framework Convention in Tobacco Control (FCTC), the first global tobacco treaty. The FCTC had been ratified by 164 countries as of April 2009, making it one of the most widely embraced treaties in the United Nations. The FCTC has spurred efforts for tobacco control across the globe by providing both rich and poor nations with a common framework of evidence-based legislation and implementation strategies known to reduce tobacco use. Jha and colleagues presented a landmark analysis in 2006 of tobacco control cost-effectiveness 19. They calculated the reductions in future tobacco deaths due to a range of tax, treatment, and nonprice interventions among smokers alive in 2000. They found that a 33% price increase would result in a reduction of

between 19.7 and 56.8 million (5.4-15.9% of total) deaths in smokers from the developing world who were alive in 2000.19 Calculations show that nicotine replacement therapy (NRT) could reduce the number of deaths by between 2.9 and 14.3 million (0.8-4.0%) in the 2000 cohort.19 A range of nonprice interventions such as advertising bans, health warnings, and smoke-free laws would reduce deaths by between 5.7 and 28.6 million (1.6-7.9% of total) in that cohort.19 These reductions would translate into developing world cost-effectiveness values of between $3 and $42 per QALY saved for tax increases (not including tax revenue), $55 to $761 per QALY for NRT, and $54 to $674 per QALY for nonprice measures.19

Salt and Lipid Reductions

The population-based intervention that is most touted as an effective means to lower blood pressure is reduction of salt intake. Average consumption of salt in the United States is 10.4 g/day,

1.1: Global Burden of Cardiovascular Disease

1.1.11

Reclassi cation of Risk Using the Reynolds Risk Score for a Representative Population of 100,000 Intermediate-Risk US Women Without Diabetes
100,000 Women With Intermediate CVD Risk 10-Year CVD Risk Stratication Using Adult Treatment Panel III Covariates45 80% 5% to <10% CVD Risk 80,000 Women 20% 10% to 20% CVD Risk 20,000 Women

Reclassication of 10-Year CVD Risk Using Reynolds Risk Score

15.9%

3.8%

55.7% 19.9% 44,560 Women 3980 Women 5% to <10% CVD Risk Low to Moderate Risk

26.9%

55.1%

1.5%

21.2%

12,720 Women 760 Women <5% CVD Risk Low Risk

21,520 Women 11,020 Women 10% to <20% CVD Risk Moderate to High Risk

1200 Women 4240 Women 20% CVD Risk High Risk

Percentages shown in ovals indicate the proportion of women distributed to risk categories based on Adult Treatment Panel III (top) and the Reynolds Risk Score (bottom). CVD indicates cardiovascular disease.

Figure 6 Reclassification of Risk Using the Reynolds Risk Score for a Representative Population of 100,000 Intermediate-Risk US Women Without Diabetes
Reproduced with permission from Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 2007;297:611-9.

of which 75% comes from processed foods. In the United States, reducing salt intake by 3 g/day (1100 mg/day of sodium) would reduce systolic blood pressure by 3.6-5.61 mm Hg for hypertensives, and in all other patients, the effect was 1.8-3.51 mm Hg.20 Meta-analyses of randomized controlled trials examining the long-term effects of salt reduction in people with and without hypertension have shown that reductions in salt intake can reduce absolute systolic blood pressure by a small but important amount.21 Effect of salt reduction on blood pressure reduction was found to be linear over the range of 0-3 g/day, for an approximate 1:1 ratio in reduction in salt intake (grams/day) and decrease in mean systolic blood pressure (mm Hg). Reducing population-wide salt consumption by only 15%through mass media campaigns and reformulation of food products by industrywould avert up to over 8.5 million deaths in 23 highburden countries over a 10-year period.21 The cost-effectiveness analyses on salt reduction as a result of public education are

quite favorable.22, 23 The intervention ranges from being costsaving to $200 per DALY averted. The results of a campaign for reducing saturated fat and replacing it with polyunsaturated fat is also likely to be cost-effective. In the base case, a 3% decline in cholesterol and $6 per capita education costs were assumed. This resulted in a cost as low as $1,800/ DALY averted in the South Asia region and up to $4,000/DALY averted in the Middle East and North Africa region. However, if the cost for the education plan were halved, the ratio would be approximately $900/DALY and would be cost-saving if the reduction could be achieved for under $0.50 per capita, which may be possible in areas with much less expensive access to media.

Community Interventions
In the 1970s and 1980s, a series of population-based community intervention studies were conducted to reduce risk factors for chronic disease and have been reviewed elsewhere.24 These focused on either changes in health behaviors or risk factors such

1.1.12

Chapter 1: General Principles

Risk Prediction Chart for Cardiovascular Disease Using NonlaboratoryBased Measures (1 of 2)

Systolic Blood Pressure (mm Hg)
171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 15-20 20-25 25-30 30-40 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 15-20 20-25 25-30 30-40

Age 65-74

Age 55-64

Age 45-54

Systolic Blood Pressure (mm Hg)

5 year cardiovascular risk (fatal and non-fatal)

15-20 20-25 25-30 30-40

Non Smoker

No Diabetes

Women
Smoker Non Smoker

Diabetes

15-20 20-25 25-30 30-40

15-20 20-25 25-30 30-40

15-20 20-25 25-30 30-40

Smoker

Low < 5% 5-10% Moderate 10-20% High 20-30% >30%

Age 35-44

How to use the Chart Choose the section with the sex, diabetes and smoking status; Find the cell that matches the patients risk factor pro le using the age, BMI, and blood pressure; Refer to physician those with excessive blood pressure (>180 mm Hg)

BMI (kg/m2)

15-20 20-25 25-30 30-40

BMI (kg/m2)

BMI (kg/m2)

15-20 20-25 25-30 30-40

BMI (kg/m2)

Figure 7a Risk Prediction Chart for Cardiovascular Disease Using NonlaboratoryBased Measures (1 of 2)
Reproduced with permission from Gaziano TA, Young CR, Fitzmaurice G, Atwood S, Gaziano JM. Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort. Lancet 2008;371:923-31.

as tobacco use, bodyweight, cholesterol, and blood pressure, as well as a reduction in CVD morbidity and mortality. In general, they included a combination of communitywide actions, as well as those focused on individuals identified as high risk. One of the earliest and most often cited community interventions is the North Karelia project, which began in 1972. The community-based interventions included health education, screening, a hypertension control program, and treatment. Over the first 5 years of the study, reductions in risk factors as well as a decline in CHD mortality of 2.9%/year versus a 1%/year decline in the remainder of Finland. During the next 10 years, declines were greater in the rest of Finland. Over 25 years of follow-up, a large decline in CHD occurred in both the North Karelia region (73%) and the remainder of Finland (63%).25 While the overall difference in the decline in CHD deaths was not significantly greater in the study area of North Karelia, the reduction in male tobacco-related cancers was significant. A similar study in the Stanford, CA, area showed reductions in risk

factorscholesterol (2%), blood pressure (4%), and smoking rates (13%) when compared to sites without the intervention but no impact on disease endpoints. Later, community interventions in high-income countries showed mixed results, with some showing improvements in risk factors beyond the secular decline that was occurring throughout most of the developed economies, and others with no additional decline. However, a meta-analysis of the randomized multiple risk factor interventions showed net significant decreases in systolic blood pressure (-4.2 mm Hg), smoking prevalence (-4.2%), and cholesterol (-0.14 mmol/L).26 The declines in total and CHD mortality of 3% and 4% were not significant. The limitation to all of the projects includes the challenge of detecting small changes that on a population level may be significant. It is possible that a 10% reduction in mortality could have been missed.26 Several community intervention studies have been conducted in developing countries, including China, Mauritius, and South Africa. The Tianjin Project showed reductions in hypertension and
1.1: Global Burden of Cardiovascular Disease 1.1.13

Risk Prediction Chart for Cardiovascular Disease Using NonlaboratoryBased Measures (2 of 2)

Systolic Blood Pressure (mm Hg)
171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 171-180 161-170 151-160 141-150 131-140 121-130 111-120 15-20 20-25 25-30 30-40

Age 65-74

Age 55-64

Age 45-54

Systolic Blood Pressure (mm Hg)

5 year cardiovascular risk (fatal and non-fatal)

15-20 20-25 25-30 30-40

Non Smoker

No Diabetes

Men
Smoker Non Smoker

Diabetes

15-20 20-25 25-30 30-40

15-20 20-25 25-30 30-40

15-20 20-25 25-30 30-40

Smoker

Low < 5% 5-10% Moderate 10-20% High 20-30% >30%

171-180 161-170 151-160 141-150 131-140 121-130 111-120 15-20 20-25 25-30 30-40

Age 35-44

How to use the Chart Choose the section with the sex, diabetes and smoking status; Find the cell that matches the patients risk factor pro le using the age, BMI, and blood pressure; Refer to physician those with excessive blood pressure (>180 mm Hg)

BMI (kg/m2)

15-20 20-25 25-30 30-40

BMI (kg/m2)

BMI (kg/m2)

15-20 20-25 25-30 30-40

BMI (kg/m2)

Figure 7b Risk Prediction Chart for Cardiovascular Disease Using NonlaboratoryBased Measures (2 of 2)
Reproduced with permission from Gaziano TA, Young CR, Fitzmaurice G, Atwood S, Gaziano JM. Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort. Lancet 2008;371:923-31.

obesity.27 The Mauritius Project, among other interventions, resulted in a government-led program that changed the prime cooking oil from a predominantly saturated fat palm oil, to a soybean oil high in unsaturated fatty acids. Overall total cholesterol levels fell 14% during the 5-year study period from 1987 to 1992. Changes in other risk factors were mixed, with declines in blood pressure and smoking rates and increases in obesity and diabetes.28 The Coronary Risk Factor Study in South Africa compared a control community to two communities receiving two different levels of intensity of interventions. The interventions included mass media messages, group-sponsored educational sessions, and blood pressure screening and follow-up with the health sector when appropriated. Both high- and low-intensity interventions showed improvements in blood pressure, smoking rates, and high-density lipoprotein (HDL) to total cholesterol ratio over the control community, but with little difference between the two intervention communities.29

One other significant reduction of CHD came not through a concerted community intervention but through changes in fiscal policy. In Poland, reductions in subsidies for animal products such as butter and lard led to a switch from saturated to polyunsaturated fats, mainly grape seed- and soya bean-based oils. A decrease in CHD mortality of >25% between 1991 and 2002 could not be explained by increased fruit consumption or declines in smoking.

Key Points
CVD accounts for approximately 30% of deaths worldwide. However, there is great variation in regional CVD mortality rates. Countries have gone through phases of the epidemiologic transition that are characterized by different life expectancies, different rates of CVD mortality, and different levels of CVD risk factors.

1.1.14

Chapter 1: General Principles

The age of degenerative and man-made diseases is distinguished by mortality from noncommunicable diseases, primarily CVD-surpassing mortality from malnutrition and infectious diseases. There is a continuous relationship between blood pressure, cholesterol levels, BMI, physical activity, and risk for CVD despite arbitrary numeric thresholds used in guidelines. Patients may have CVD events despite some individual risk factors being in the normal range, due to the overall combined high risk from all risk factors. Three complementary types of interventions have occurred in high-income countries to result in large reductions in age-adjusted CVD mortality rates: 1. Targeting patients with acute or established CVD, 2. Risk assessment and identifying those at high risk due to
multiple risk factors for intervention before their first CVD event, and

References
1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ, eds. Global Burden of Disease and Risk Factors. New York: The World Bank and Oxford University Press; 2006: 552. Gaziano JM. Fifth phase of the epidemiologic transition: the age of obesity and inactivity. JAMA 2010;303:275-6. Lawes CM, Hoorn SV, Rodgers A. Global burden of blood-pressurerelated disease, 2001. Lancet 2008;371:1513-8. Whitlock G, Lewington S, Sherliker P, et al., on behalf of the Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96. Gaziano TA. Cardiovascular disease in the developing world and its cost-effective management. Circulation 2005;112:3547-53. Gaziano TA, Opie LH, Weinstein MC. Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis. Lancet 2006;368:679-86. Gaziano TA, Steyn K, Cohen DJ, Weinstein MC, Opie LH. Cost-effectiveness analysis of hypertension guidelines in South Africa: absolute risk versus blood pressure level. Circulation 2005;112:356976. Ferrario M, Chiodini P, Chambless LE, et al. Prediction of coronary events in a low incidence population. Assessing accuracy of the CUORE Cohort Study prediction equation. Int J Epidemiol 2005;34:413-21. Wilson PW, DAgostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

2. 3. 4.

5. 6.

7.

8.

3. Mass education or policy interventions directed at the entire

population to reduce the overall level of risk factors. 9.

Primary prevention is paramount for the large number of individuals who are at high risk for CVD. A cost-effective primary prevention strategy includes use of prediction rules or risk scores to identify those at higher risk in order to target specific behavioral or drug interventions. Risk scores typically include age, sex, hypertension, smoking status, diabetes mellitus, and lipid values. Some also include family history. Some risk scores do not require laboratory testing. Education and public policy interventions that have reduced smoking rates, lowered mean blood pressure levels, and improved lipid profiles, have contributed to the reduction in CHD rates.

10. Folsom AR, Chambless LE, Ballantyne CM, et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: The Atherosclerosis Risk in Communities Study. Arch Intern Med 2006;166:1368-73. 11. Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction offirst Major cardiovascular events and death. N Engl J Med 2006;355:2631-9. 12. Ware JH. The limitations of risk factors as prognostic tools. N Engl J Med 2006;355:2615-7. 13. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 2007;297:611-9.

1.1: Global Burden of Cardiovascular Disease

1.1.15

14. Lindholm LH, Mendis S. Prevention of cardiovascular disease in developing countries. Lancet 2007;370:720-2. 15. Mendis S, Lindholm LH, Mancia G, et al. World Health Organization (WHO) and International Society of Hypertension (ISH) risk prediction charts: assessment of cardiovascular risk for prevention and control of cardiovascular disease in low and middle-income countries. J Hypertens 2007;25:1578-82. 16. Gaziano TA, Young CR, Fitzmaurice G, Atwood S, Gaziano JM. Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort. Lancet 2008;371:923-31. 17. Ford ES, Ajani UA, Croft JB, et al. Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000. N Engl J Med 2007;356:2388-98. 18. Asaria P, Chisholm D, Mathers C, et al. Population-wide interventions to prevent chronic diseases. Lancet 2007;370:2044-53. 19. Jha P, Chaloupka FJ, Moore J, et al. Tobacco Addiction. In: Jamison DT, Breman JG, Measham AR, et al. Disease Control Priorities in Developing Countries. 2nd ed. New York: Oxford University Press; 2006. 20. Bibbins-Domingo K, Chertow GM, Coxson PG, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med 2010;362:590-9.

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1.1.16

Chapter 1: General Principles