Introduction
Cardiovascular disease (CVD) was the single most important cause of death worldwide in 2013, when it was responsible for 17 million deaths and the loss of 329 million disability-adjusted life-years (DALYs). Of all causes of CVD, ischemic heart disease (IHD) remains the major contributor, accounting for half of all CVD-associated morbidity and mortality. IHD as measured by the Global Burden of Disease project is driven predominantly by acute myocardial infarction (MI) and, to a lesser extent, angina. Over the past two decades, while age-standardized IHD mortality in most world regions has decreased, the global burden of IHD has increased by 29 million DALYs (representing a 29% increase), owing in large part to overall population growth and to the aging of the population.
This chapter presents a review of the global burden of IHD, with an emphasis on low- and middle-income countries (LMICs). Also considered are the trends in management of acute MI. Concluding the chapter is a discussion of challenges that IHD poses to the global community and solutions that may help to reduce IHD morbidity and mortality.
Data Sources
Data for mortality and DALYs come from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD), which obtained and analyzed mortality data for 187 countries from 1980 to 2010, and the World Health Organization (WHO) Mortality Data Base. Although the GBD study made extensive efforts to standardize mortality data, these estimates should be interpreted cautiously, because the methodology of coding deaths varies globally, potentially leading to significant misclassification. The World Bank has divided the world into seven regions: one region consisting of high-income countries (HICs) and six geographic regions consisting of low- and middle-income countries (LMICs). The information on demographic and social indices presented here is from the World Bank’s World Development Indicators (WDIs), and data on gross national income (GNI) per capita were derived using the Atlas method in 2011 U.S. dollars (USD).
Mortality and Morbidity Due to Myocardial Infarction
Age-adjusted IHD death rates in HICs are declining; however, the current high burden of IHD is primarily the consequence of deaths among 85% of the world’s population living in LMICs ( Figure 2-1 ). Globally, between 1990 and 2010, the age-adjusted death rate decreased by 21% from 131/100,000 to 106/100,000, but the number of IHD-associated deaths is increasing. In this same period, the number of deaths increased by 35%. Approximately a third of the increase in DALYs attributable to IHD is due to aging of the world population, and another 22% is due to population growth. Globally, the incidence of acute MI declined over the period 1990 to 2010, dropping from 222.7/100,000 to 195.3/100,000 for males and from 136.3/100,000 to 115.0/100,000 for females ( Figure 2-2 ). The greatest declines occurred in HICs, with only modest declines in LMICs, whereas increases in acute MI incidence were observed in Eastern Europe ( Figure 2-3 ). Despite a meaningful decline in age-adjusted IHD deaths, the DALYs lost due to IHDs have decreased only marginally, by 0.6%, from 1895/100,000 to 1884/100,000.
The reduction in MI mortality appears to be a result of a reduction in both the age-adjusted MI incidence and the case-fatality rate. In a study of the four communities in the Atherosclerosis Risk in Communities (ARIC) Study in the United States, rates in both in-hospital and out-of-hospital mortality declined. Over the period 1987 to 2008, the age-adjusted MI incidence decreased in black and white men and in women, but at different rates. Adjusted for biomarkers, the rates of decline were 4.3%, 3.8%, 2.9%, and 1.5% among white men, white women, black women, and black men, respectively. Age-adjusted in-hospital deaths declined annually by an average of 7.2% for men and 6.9% for women, with most of the reductions coming in the later years (1997 to 2008) compared with the earlier time period (1987 to 1996). Out-of-hospital mortality also declined by 4.9% and 3.7% per year for men and women, respectively. The Kaiser Permanente Northern California health care system reported a 24% decline in MI incidence from 1999 to 2008. This reduction was almost entirely driven by reductions in ST-elevation MIs (STEMIs) from 133 per 100,000 person-years in 1999 to 50 per 100,000 person-years in 2008 ( Figure 2-4 ). Thirty-day mortality also declined, with an odds ratio of 0.76 on comparing 2008 rates to 1999 rates. Over a similar time period in the Worcestor, Massachusetts area, STEMI incidence declined by nearly 50%, with no significant change in that of non ST-elevation MI (NSTEMI). In England, the reduction in MI mortality appears to be split between reductions in MI incidence and in case-fatality rate. From 2000 to 2010, MI case-fatality rates dropped by approximately 3.6% and 4.2% annually, respectively, for men and women, and MI incidence declined by 4.8% and 4.5%, respectively, for men and women. Similarly, over a 25-year period (1984 to 2008) in a large Danish study of more than 234,000 patients with first-time MI, MI incidence declined by 48% and 37% for men and women, respectively, and 30-day mortality declined by greater than 50% in both men and women in the same time period ( Figure 2-5 ).
In addition to the decline in incidence and case-fatality rates over recent decades, the morbidity associated with MI also has changed. For example, patients with MI in Olmsted County, Minnesota, presented with lower severity of heart failure despite more comorbid conditions. Furthermore, the incidence of heart failure (HF) developing both early (within 7 days of MI) and late (8 days up to 5 years later) declined dramatically by 5.7% and 5.8%, respectively, in absolute terms over the time frame 1990 to 1996, compared with 2004 to 2010 (see Chapter 25 ). The entire decline was accounted for by a decreased frequency of HF associated with reduced ejection fraction, because no decline was observed in the risk of HF with preserved ejection fraction after MI. An analogous decline in HF during the index admission for MI also was seen in Worcester, Massachusetts, after 1991.
Variation in the Global Burden of Ischemic Heart Disease
Although global trends show a larger IHD burden in LMICs in comparison with HICs, significant variation in IHD burden is evident across the six LMIC regions, and among countries within a given region or World Bank income category. Described next are those regional variations in acute MI incidence and burden.
High-Income Countries
For the GBD 2010 Study, HICs were divided into five regions: Asia Pacific, High Income; Europe, Western; Australasia; North America, High Income; and Latin America, Southern. Among males in 2010, the regions from highest to lowest in terms of MI incidence per 100,000 were Latin America, Southern (194.47), North America (191.28), Western Europe (191.04), Australasia (185.21), and Asia Pacific, High Income (106.84). Among females the MI incidence rates were lower with the rate per 100,000 females in each region: Latin America, Southern (95.15), North America (98.91), Western Europe (88.24), Australasia (93.61), and Asia Pacific, High Income (50.77). In all regions the male-to-female ratio was approximately 2:1 ( Figure 2-6 ). All of these regions had declines of approximately 22% (Asia Pacific) to 40% (Europe, Western) from 1990 rates. The age-standardized loss in DALYs attributed to IHD decreased, with Japan, South Korea, and France reporting the lowest DALYs lost among high-income countries.
Low- and Middle-Income Countries
East Asia and the Pacific
In 1990, IHD was the fourth major cause of death in the East Asia and Pacific (EAP) region, but by 2010, it was the leading cause. The MI incidence varied among the EAP subregions in 2010, ranging from highest at 212/100,000 males in Oceania, to167/100,000 males in Southeast Asia, and lowest at 133/100,000 males in East Asia. The rates mildly declined by approximately 10% in Oceania and Southeast Asia and remained similar to those reported in 1990 in East Asia. For women, as in the HICs, overall incidence was lower than in men. Rates of MI/100,000 females were 130, 101, and 78 for Oceania, Southeast Asia, and East Asia, respectively. Southeast Asian women had a 20% decline, and East Asian women saw only mild declines in their incidence rates. Oceanian women saw a mild increase compared with 1990. Furthermore, CVD accounts for the largest proportion of DALYs lost in the region, with 26 million lost in Southeast Asia and 67 million lost in East Asia.
Central and Eastern Europe and Central Asia
The highest CVD mortality rate occurs in this region and was 866/100,000 in Eastern Europe and 604/100,000 in Central Europe. As seen in other regions, the number of CVD-related deaths varies across countries. In Ukraine, Bulgaria, Belarus, and Russia, CVD rates have reached an alarming 800/100,000 for men. Also as in other regions, the largest component of CVD mortality is acute MI. MI incidence is highest in the world, at 410/100,000 males in Eastern Europe, followed by 341/100,000 males in Central Asia and 265/100,000 males in Central Europe. Rates for males increased by 16% in Eastern Europe, mildly increased in Central Asia, and declined by 30% in Central Europe. The incidence rates per 100,000 females were 199, 189, and 138 for Eastern Europe, Central Asia, and Central Europe, respectively. Like the males, females in Central Europe demonstrated a large 25% decline in incidence, with 10% increase in Eastern Europe and a minimal decline of 3% in Central Asia.
Latin America and the Caribbean
The Latin America and Caribbean (LAM) region has a high CVD burden ; in 2010, CVD was responsible for 29% of all deaths, and IHD was the leading cause of DALYs lost, representing a 36% increase over 1990 rates. Rates of MI incidence in 2010 were similar per 100,000 males in Central America (198), Tropical Latin America (205), and Caribbean Latin America (210) and considerably lower in the Andean subregion (149). Declines in incidence in this region ranged from nearly 20% in Tropical Latin America to only approximately 7.5% in Central America. For women, the Caribbean rate was highest at 140/100,000, compared with 124/100,000, 119/100,000, and 102/100,000, respectively, for Central America, Tropical Latin America, and the Andean subregion. Declines were similar to those for males across the region compared with 1990 data.
North Africa and the Middle East
In 2010, IHD accounted for 93 deaths per 100,000 population, representing a 15% increase in IHD mortality rates. In addition to increased mortality, CVD and IHD were responsible for 17.2 million and 6.8 million DALYs lost, respectively. Individual country data show that 12 of the 19 countries in North Africa and the Middle East are ranked in the top 50 countries worldwide for age-adjusted IHD mortality rates. Overall, the region had an MI incidence rate of 257/100,000 males and 153/100,000 females in 2010. These rates represented 20% and 15% decreases, respectively, for males and females since 1990.
South Asia
CVD accounts for 20% of all deaths in the South Asian Region (SAR), of which IHD is responsible for more than 50%. In 2010, IHD was responsible for 1.8 million deaths, or 10.6% of all fatalities. In addition to mortality, CVD also was responsible for 60.5 million of DALYs lost in 2010. India, with a population of 1.2 billion, is the largest country within this region and has an extremely high burden of IHD. In 1990, 1.18 million people died from IHD; this increased to 2.03 million in 2010, and it is estimated that CVD represents 25% of deaths in India. South Asia has the third highest MI incidence of all regions, with 245/100,000 in males and 155/100,000 in females. Women have seen an approximately 8% decline, whereas the rate for men declined by little over 3% compared with 1990 rates.
Sub-Saharan Africa
Of all the subregions in sub-Saharan Africa, Southern Africa has the highest number of CVD deaths, currently at 13%; in Western Africa, CVD accounts for 7.5% of all deaths. Overall, across sub-Saharan Africa, the mortality rates are lower than global averages, with the exception of Southern Africa, where the rates have increased from 129/100,000 to 136/100,000. Sub-Saharan Africa is divided into Central, East, Southern, and West subregions. For men, the MI incidence rates per 100,000 are 223, 172, 174, and 181, respectively. For women, the rates are 165, 139, 118, and 147, respectively. For both men and women in West and Central Africa, there was either no change or mild increases in MI incidence compared with 1990 rates. Men and women in East and Southern sub-Saharan Africa saw drops in MI incidence of approximately 10% from 1990 rates. As part of the WHO’s Global Action Plan for Prevention and Control of Noncommunicable Diseases 2013-2020, it is estimated that a combination of cost-effective health interventions, with an implementation cost of $1 per capita in low-income countries (LICs) and up to $3 per capita in HICs, could help to reduce the burden of CVD and diabetes in Africa.
Economic Burden of Ischemic Heart Disease
The economic burden of IHD is significant and can be measured in at least three ways: first, by financial costs incurred in the health care system and described in “cost-of-illness” studies; second, by microeconomic studies that assess the household impact of health events such as MIs; and, third, by macroeconomic analyses that assess worker productivity or loss of economic growth from individual patients or their caregivers being partially or completely out of work as a consequence of illness. The literature on the first and second measures in LMICs is sparse, and no published microeconomic studies have focused exclusively on IHD. Many LMICs lack extensive insurance plans, and government-funded plans may be inadequate, requiring people to pay out of pocket for health services in the acute setting, for medications, and for outpatient follow-up care.
Relatively more information is available on the economic burden from a macroeconomic perspective. The LIMCs are earlier in the epidemiologic transition, so IHD occurs at younger age than in HICs. Accordingly, although data are limited, the macroeconomic burden for each IHD event is likely to be higher. In China, annual direct costs of CVD are estimated at more than $40 billion, which translates into 4% of their GNI. In South Africa, 25% of the health care expenditure is devoted to CVD. Relatively few cost-of-illness studies have been done in other regions of the world, but information on the costs associated with risk factors for IHD is available. Globally, health care costs related to hypertension were estimated at $370 billion in 2001, a staggering figure that was estimated to increase to $1 trillion in direct costs and up to $4 trillion for indirect costs by 2011, or nearly a doubling over a decade. Although the cost of managing risk factors is immense, the cost of long-term management of IHD is equally high. Heart failure, the most common sequela of IHD, is estimated to cost $108 billion annually.
Interventions
Success in reducing CVD mortality rates depends on improved primary and secondary prevention strategies (see Chapter 34 ). Approximately 25% to 50% of the reduction in CVD-associated mortality is related to treatments, and the remainder is due to changes in risk factors. Improvements in acute care reduce case fatality but also increase the chronic IHD population in need of secondary prevention. Considered next are individual-level interventions for management of MI globally and their cost-effectiveness ( Table 2-1 ).
| Intervention | Source for Estimate: Country or World Bank Regions Studied | Low-Income Countries (GNI per capita ∗ : ≤$1045) | Middle-Income Countries (GNI per capita ∗ : $1045 to $12,746) | ||
|---|---|---|---|---|---|
| Very Cost-Effective Up to 1× GNI/QALY | Cost-Effective Up to 3× GNI/QALY (up to $3135) | Very Cost-Effective Up to 1× GNI/QALY | Cost-Effective Up to 3× GNI/QALY (up to $38,238) | ||
| Aspirin + beta blocker | All non–high-income regions | $11 to $22 | |||
| Aspirin + beta blocker + SK | All non–high-income regions | $634 to $734 | |||
| Aspirin + beta blocker + tPA | All non–high-income regions | $15,860 to $18,893 | |||
| Aspirin + beta blocker + statin + ACE inhibitor | All non–high-income regions | $300 to $400 | |||
| † Aspirin + beta blocker + statin + ACE inhibitor | China | $ 3100 | $ 3100 | ||
| † Clopidogrel | China | $17,600 | |||
| † Primary PCI | China | $9000 to $23,000 | |||
| Coronary artery bypass graft surgery | South Asia, sub-Saharan Africa, and East Asia and the Pacific | $24,040 to $33,846 (ICER compared with four medications: aspirin, beta blocker, statin, and ACE inhibitor) | |||
| Nicotine replacement therapy | All non high-income regions | $55 to $761 | |||
| Community pharmacist–based smoking cessation program | Thailand | Men : $500 with 0.18/LY gained Women : $614 with 0.24/LY gained | |||
| Nicotine-based gum | Seychelles | $599 | |||
| Bupropion-based | Seychelles | $227 | |||
| ICD | United States | $17,000 | |||
| CRT in heart failure | Brazil | I$15,723 | |||
| CRT | Argentina | I$34 (ICER compared with medical therapy) | |||
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