The Global Perspective of Ischemic Heart Disease

Introduction

Cardiovascular disease (CVD) and specifically ischemic heart disease (IHD) have long been the leading cause of death in high-income countries (HICs); indeed, “disease of the heart,” in all its manifestations, has topped the Centers for Disease Control and Prevention cause of death list since 1921. Coronary artery disease accounts for the majority of this disease burden.

With the progression of global development, the burden of CVD has increasingly been borne by low- and middle-income countries (LMICs), with up to 80% of CVD deaths worldwide occurring in LMICs. The shifting burden of CVD, first encountered in HICs and increasingly affecting the developing world, is the result of the epidemiologic transition and represents the contribution of sanitation, public health, industrialization, urbanization, and economic advances, leading to a reduction in the burden of infectious disease on the one hand and an increase in CVD risk factors on the other hand.

Epidemiologic Trends

The epidemiologic transition consists of four basic stages ( Fig. 2.1 ): pestilence and famine, receding pandemics, degenerative and man-made disease, and delayed degenerative diseases. The current trend in CVD burden is being driven by the transition of LMICs to stage 3 of this transition, namely the phase of degenerative and man-made disease. In this stage, improvement in economic circumstances, as well as increased urbanization with its attendant sociopsychologic stresses, results in altered dietary patterns, decreased activity levels, and an increase in behaviors associated with CVD, including smoking. These changes lead to an increase in atherosclerosis and resultant CVD; between 35% and 65% of all deaths in this stage are attributable to CVD, with IHD the predominant cause. The majority of CVD deaths in this stage are seen among individuals of higher socioeconomic status, as they are the first to benefit from these improvements in circumstance.

FIG. 2.1, Stages of epidemiologic transition. CVD, Cardiovascular disease; CHF, congestive heart failure; IHD, ischemic heart disease; RHD, rheumatic heart disease; Tx, therapy.

High-income countries currently occupy the fourth stage of the transition: delayed degenerative diseases. In this stage, primary and secondary prevention measures, as well as new therapeutic approaches, lead to significant decreases in age-adjusted mortality rates. CVD still accounts for between 40% and 50% of all deaths in this stage, though largely affecting older individuals. Importantly, the burden of premature CVD in HICs shifts to lower levels of socioeconomic status, as those of higher status are first to benefit from improvements in the measures noted previously.

Importantly, there is mounting evidence of a possible fifth stage: the age of obesity and inactivity. In some HICs, declines in age-adjusted mortality rates of CVD have leveled off, with improvements in rates of smoking and hypertension plateauing and with increasing rates of obesity and its associated consequences, including diabetes and dyslipidemia. Although the trends are for continued age-adjusted declines in mortality, some increases in risk factors particularly evident in children have the potential to reverse gains in age-adjusted CVD mortality in the coming years.

Burden of Disease

With the global advancement through the epidemiologic transition, the primary drivers of global mortality have shifted from malnutrition, infectious disease, and infant and child mortality to more chronic, noncommunicable diseases. In the most recent survey of the Global Burden of Disease (GBD) in 2010, noncommunicable diseases comprised 65.5% of all deaths worldwide and approximately 43% of years of life lost (YLL), a measurement of amount of life lost due to premature mortality. Chief among this advanced class of maladies stands CVD, and within this category, IHD, as the primary cause of mortality worldwide. Indeed, IHD has remained the top-ranked cause of mortality worldwide from 1990 to 2010, and in 2010 overtook lower respiratory tract infections as the top-ranked cause of both YLL and disability-adjusted life years (DALYs). In 2010, IHD was the cause of 13.3% of all deaths globally.

IHD manifests in three clinical presentations: chronic stable angina, ischemic heart failure, and acute myocardial infarction (AMI). Whereas YLL secondary to AMI make up the largest portion of DALYs lost to IHD (94% in men, 92% in women) ( Fig. 2.2 ), IHD drives a growing number of years lived with disability (YLDs) as a result of chronic stable angina, ischemic cardiomyopathy, and nonfatal AMI. The largest proportion of YLD due to IHD is secondary to chronic stable angina, which in 2010 was prevalent in 20.3 per 100,000 males and 15.9 per 100,000 females. Ischemic heart failure, an increasingly important outcome in chronic IHD, was prevalent in 2.7 males and 1.9 females per 100,000. Disability due to nonfatal AMI, consisting of the period up to 28 days post-AMI, was responsible for a small fraction of YLDs due to IHD ( Fig. 2.3 ).

FIG. 2.2, Disability-adjusted life years (DALYs) secondary to ischemic heart disease. YLL, Years of life lost; YLD, years lived with disability.

FIG. 2.3, Cause-specific years lived with disability (YLDs) secondary to chronic ischemic heart disease.

Importantly, the epidemiologic transition underlies the trends in the incidence and prevalence of IHD and its growing burden of disease worldwide. Globally, the number of deaths due to IHD increased from 5.2 million to 7 million from 1990 to 2010, though in the same time period age-adjusted death rates decreased from 131.3 to 105.7 per 100,000, an almost 20% improvement. Similarly, YLDs secondary to all chronic sequelae of IHD increased from 1990 to 2010: chronic angina from 5 million to 7.2 million (44% increase), ischemic cardiomyopathy from 890,000 to 1.5 million (70% increase), and nonfatal AMI from 29,000 to 42,000 (45% increase). As with mortality secondary to fatal AMI, age-standardized prevalence of chronic stable angina and nonfatal AMI fell from 1990 to 2010, though there was a slight increase in the age-standardized prevalence of ischemic cardiomyopathy. Despite the almost universal improvement in age-standardized incidence and prevalence of IHD, the absolute global burden of IHD measured in DALYs increased by 29% from 1990 to 2010. This increase was driven primarily by the aging of the world’s population and increasing size of the population, accountable for 32.4% and 22.1% of the growth of DALYs, respectively. These changes were attenuated by an overall decrease of 25.3% in the age-adjusted IHD DALY rate. Notably, in LMICs, the increase in IHD DALYs was driven primarily by the increasing size of the population, whereas in HICs, the increase was largely due to the increasing age of the population.

Data on incident AMI and prevalent IHD are well documented; however there is a significant body of evidence that suggests that coronary atherosclerosis, the etiology of IHD, has a long detectable preclinical phase. The biologic onset of disease occurs long before the manifestation of symptoms, resulting in a lengthy asymptomatic disease state. Efforts to characterize patients as low-, intermediate-, and high-risk for the development of IHD have been established through the use of risk scores. However, diagnosis prior to clinical onset of disease is largely prohibitive due to the invasive nature of the gold standard for IHD diagnosis, coronary angiography. Recent technical advances have resulted in the introduction of coronary computed tomography (CT) angiography to assess coronary artery calcification and stenosis. The modality has been shown to be highly sensitive and specific for the detection of greater than 50% stenosis versus coronary angiography. In multiple large-scale trials, CT screening of middle-aged patients between 45 and 74 years old with no history of IHD was revealing for any degree of coronary artery calcification in one-half to two-thirds of people screened. These numbers may be reflective only of asymptomatic IHD in HICs, though with the continued advancement of LMICs through the epidemiologic transition, this may soon be representative of larger swaths of the global population. Indeed, in a postmortem study of coronary artery atherosclerosis in northern India, stenosis was found in approximately 30% of cases (mean age 35 years); of these, approximately two-thirds of cases were nonobstructive, with narrowing of less than 50% of the coronary lumen. These results are consistent with the growing disease burden of IHD in LMICs.

Disease Burden by Region

With the progression of societies through the epidemiologic transition, larger proportions of IHD morbidity and mortality are borne by LMICs as previously discussed. In this section, we will detail incidence, prevalence, and trends in IHD in distinct regions as defined by the GBD study. Figs. 2.4 and 2.5 depict regional variation in YLD and total DALYs lost to IHD, respectively. Figs. 2.6 and 2.7 graphically display temporal trends in IHD DALYs and proportion of DALYs driven by YLDs by GBD region, respectively. Data in this section on social and demographic indices in these regions are derived by World Bank World Development Indicators.

FIG. 2.4, Years lived with disability secondary to chronic ischemic heart disease per 100,000 population by region.

FIG. 2.5, Disability-adjusted life years secondary to chronic ischemic heart disease per 100,000 population by region.

FIG. 2.6, Ischemic heart disease disability-adjusted life years per 100,000 persons.

FIG. 2.7, Percent ischemic heart disease disability-adjusted life years secondary to years lived with disability.

High-Income Countries

Social and Demographic Indices

Over 1 billion people live in HICs as defined by the GBD, including the regions of southern Latin America, Western Europe, high-income North America, Australasia, and high-income Asia Pacific. Of these countries, the largest is the United States, with approximately 318 million inhabitants. People in these countries enjoy relatively long life expectancies, with men born in this region in 2013 expected to live approximately 80 years and women 83 years. The median percentage of the population over 65 in these countries is 17%, though there is a significant range, from 10% in southern Latin America to greater than 18% in Western Europe. Notably, greater than 25% of the population of Japan is over the age of 65. The median gross national income (GNI) per capita and health expenditure per capita in this region are $46,550 and $3965, respectively. Median public spending on health expenditures as a percent of total spending is approximately 75%.

Disease Burden and Trends

There is great heterogeneity in the epidemiology of IHD throughout this region. HICs as a group enjoyed the lowest number of DALYs lost to IHD per population in 2010, from a low of 654 per 100,000 persons in high-income Asia Pacific, to 1636 in high-income North America. As a share of total morbidity and mortality, IHD was responsible for 4.7% of DALYs in this region in 2010. By comparison, this number was 7.88% in 1990. High-income Asia Pacific again bears the lowest percent of DALYs attributed to IHD at 2.7%, compared to 6.1% in high-income North America. It is worth noting that the high-income Asia Pacific region bears an aberrantly high stroke burden, with ischemic stroke driving almost half of the CVD burden in this region. This is compared to a greater than 2:1 global ratio in favor of IHD over stroke in CVD mortality.

As previously mentioned, the primary driver of DALYs lost secondary to IHD is YLL due to AMI. Of over 21 million DALYs lost to IHD in HICs in 2010, just over 10% were due to morbidity associated with IHD, including nonfatal AMI, angina, and ischemic cardiomyopathy. In 1990, this number was less than 7%, which belies the shifting burden of IHD from acute events to a chronic condition. YLDs in the high-income Asia Pacific region drove more than 15% of DALYs in 2010, as compared to less than 9% in high-income North America and southern Latin America. The mean age of onset of angina rose from 60.2 to 62.2 from 1990 to 2010, and its mean duration of 14 years did not change in the interceding decades. Mean age of first AMI rose from 69.9 to 71.4.

With advancement through the stages of epidemiologic transition, much of the improvement in IHD morbidity and mortality can be attributed to better preventive and therapeutic measures resulting in the decrease in age-standardized incidence and prevalence of IHD. The age-standardized incidence rates of AMI fell from 245 to 173 males per 100,000 and 119 to 85 females per 100,000 from 1990 to 2010. Incidence rates of angina similarly fell from 24 to 18 in males and 17 to 13 in females per 100,000. Notably, though, prevalence rates of ischemic cardiomyopathy increased during this same time frame, albeit as a less common outcome than either AMI or angina: 3.2 to 3.7 males and 2 to 2.3 females per 1000 persons.

Despite the improvement in age-standardized rates of morbidity and mortality secondary to IHD described, the global burden of IHD continues to rise. The exception to this phenomenon is in HICs, where not only age-adjusted rates of IHD but absolute IHD DALYs have fallen from 1990 to 2010 in three—Western Europe, high-income North America, and Australasia—of five regions in this grouping, with total burden remaining relatively stable in high-income Asia Pacific and southern Latin America. Total burden of DALYs due to IHD has fallen more than 30% in Western Europe, 28% in Australasia, and 17% in high-income North America due to large improvements in age-adjusted incidence; in Australasia, the age-adjusted incidence rate of IHD has been nearly halved in 20 years. High-income Asia Pacific additionally has seen dramatic reductions in age-adjusted incidence rates—approximately a 75% decrease. However, total burden of IHD DALYs has risen 10% due to a sharp increase in aging of the population.

Eastern Europe/Central Asia

Social Indices

There are 400 million inhabitants of the Central and Eastern Europe and Central Asia regions. The population is evenly divided among these three regions, with Russia being the largest individual nation by population with 140 million people. This region has a high median percentage of the population over 65 at approximately 14%; however, this number masks vast differences in the population makeup between regions. Whereas Eastern and Central Europe have greater than 15% and 16% of persons over the age of 65, respectively, this number is only 4.6% in Central Asia. Median life expectancy across the region is approximately 71 years in men and 78 years in women, though men in Central Asia and Eastern Europe have life expectancies of 66 years and 67 years, respectively. Median GNI per capita is $7590, ranging from $13,220 in Eastern Europe to $4020 in Central Asia. Median health expenditure in the region is $462, which represents 6.5% of gross domestic product (GDP). Public spending makes up 60% of total health expenditures in the region.

Disease Burden and Trends

The Eastern Europe/Central Asia region holds the highest burden of DALYs secondary to IHD globally. Age-adjusted DALYs per 100,000 persons numbered 4614 in 2010, a figure that has not seen much change in two decades (4741 per 100,000 persons in 1990). The majority of disease in this region is driven by Eastern Europe and Central Asia, both of which have seen increases in IHD DALY rates from 1990 to 2010 and currently rank first and second in IHD DALY rates by region at 5776 and 5459 IHD DALYs per 100,000, respectively. These numbers represent 12.8% and 15.3% of total DALYs in these regions. Indeed, these are the only two regions globally where the rate of rise of YLLs outpaced increases in YLDs as they contribute to total IHD DALYs. YLDs secondary to IHD account for 3.65% in Eastern Europe and 4.08% in Central Asia. Central Europe, by contrast, has not only seen improvement in its age-adjusted rate of IHD DALYs per 100,000 persons from 3936 to 2608, but also a decrease in total burden of IHD DALYs from 1990 to 2010, the only non-HIC region to earn such a distinction. IHD DALYs account for less than 8% of total DALYs in this region, and an increasing proportion of DALYs is due to YLDs, from 4.11% in 1990 to 5.54% in 2010.

The mean age of onset of angina in this region is 60 years, ranging from 56 years in Central Asia to 62.3 years in Central Europe. The incidence of angina has remained stable overall in the region as a whole, at 30.5 and 22 per 100,000 men and women, respectively, in 2010. The mean age of incident AMI is 69.5, distributed from young (66.6) in Central Asia, to old (71.9) in Central Europe. The incidence of AMI has fallen for the region as a whole from 1990 to 2010 in both men and women from 343 to 338 and 186 to 175 per 100,000 persons, though it has risen for men in both Eastern Europe and Central Asia, as well as for women in Eastern Europe; these trends have been offset by greater improvement in AMI incidence in Central Europe. The prevalence of ischemic cardiomyopathy has increased for both men and women in all regions, and averages 4 per 1000 persons in men (5.5 in Eastern Europe, 3.0 in Central Europe) and 2 per 1000 persons in women.

The gains noted in Central Europe have been made by a decrease in age-adjusted rates of IHD DALYs of greater than 40%, resulting in an actual 12% improvement in IHD DALYs from 1990 to 2010. In contrast, age-adjusted rates in Central Asia have remained flat, and have increased in Eastern Europe by greater than 15%. Increases in actual IHD burden in these two regions total greater than 37% and 31%, respectively. Population growth and aging of the population have combined to result in the increase in actual IHD DALYs in Central Asia, whereas the aforementioned increase in age-adjusted rates of disease and aging of the population has driven the increase in Eastern Europe; notably, this region has seen a net decrease in the population of greater than 6% from 1990 to 2010. Central Europe, too, has seen a net negative decline in total population, with aging of the population offsetting some of the gains made in age-adjusted mortality rates.

Latin America/Caribbean

Social Indices

There are over 550 million people living in the Latin America/Caribbean region, which includes the Caribbean, central, tropical, and Andean regions of Latin America. Median life expectancy in the region is 70 in men and 77 in women, and 6.8% of the population is over 65. Median GNI in the region is $6770, and median health expenditure per capita is $431 annually; this ranges from $76 in Haiti to over $1000 in Brazil, Costa Rica, the Bahamas, and Barbados. Health expenditure represents 6.5% of GDP, and 57% of that figure stems from public spending.

Disease Burden and Trends

The Latin America/Caribbean grouping bears a relatively low rate of IHD DALYs as a region, ranging from 1144 in Andean Latin America to 2169 in the Caribbean. There has been improvement in the age-standardized IHD DALYs as a whole over two decades, from 2216 in 1990 to 1699 per 100,000 persons in 2010, representing 5.25% of total DALYs lost in the region. The percent that IHD DALYs contribute to total DALYs has remained stable over this time period; however this masks changes in disease proportions in subregions. Central and Andean Latin America have seen relative increases in the proportion of DALYs lost secondary to IHD, from 6.1% to 6.7% and 3.5% to 4.2%, respectively, from 1990 to 2010. In contrast, the Caribbean saw a dramatic decline in the percent of DALYs attributable to IHD, from 6.3% to 5.3%; although this region did see improvement in age-adjusted rates of IHD DALYs per population, this likely reflects the large increase in DALYs lost secondary to natural disaster in the setting of the 2010 Haiti earthquake. In addition to overall improvement in age-adjusted IHD DALY rates, an increasing proportion of DALYs in this region is being driven by YLDs, from 6.5% to 8.1% between 1990 and 2010. This percentage is highest in tropical Latin America at 9.3% and lowest in the Caribbean at 5.6%.

The mean age at onset of angina in this region is 57 years, and mean duration is 16 years. Mean age at incident AMI is 67 years. There has been a stable to mildly decreased incidence rate of angina, from 20.9 to 19.2 per 100,000 in men and 17 to 15.3 in women from 1990 to 2010. The AMI incidence rate has similarly trended down, from 219 to 191 in men and 144 to 121 in women per 100,000 over the same time period. Rates of ischemic cardiomyopathy have increased in this region as they have globally, from 1.47 to 1.77 per 1000 in men and 1.32 to 1.51 per 1000 in women.

The region as a whole has seen an increase in absolute DALYs lost to IHD primarily due to an increase in population growth and aging of the population. For instance, despite an improvement by over 30% in the age-adjusted rate of IHD morbidity and mortality in Central Latin America, actual IHD DALYs have jumped 62.2%, with over 50% change due to aging of the population and approximately 40% due to population growth. This story is similar in other parts of the region, with the exception of the Caribbean, which has seen little population growth at 3.4% and thus has had the lowest increase in actual rates of IHD DALYs at 22%.

East Asia/Pacific

Social Indices

Over 2 billion people live in the East Asia, Southeast Asia, and Oceania regions, including 1.36 billion in China alone. Median life expectancy in men is 67 years and in women 73 years. The median percentage of the population over 65 in the region as a whole is 5.18, but it is notably 9.18 in China. Median GNI per capita is $3460, and median health expenditure per capita is $123. Health expenditures represent a median 4.57% of GDP in the region, of which 67% is public spending.

Disease Burden and Trends

The East Asia/Pacific region, including populous China, has a combined IHD DALY rate of 1759 per 100,000 persons, which has been stable for the past two decades. The East Asia region, which includes China, has a lower rate at 1242, whereas Oceania has the highest rate in the region at 2324. IHD DALYs represent 5.2% of total DALYs lost in the superregion, and of them, 9% are due to YLD secondary to IHD. Notably, YLDs in East Asia contribute over 10% to total IHD DALYs, and in total number nearly 1.9 million YLD due to IHD; South Asia and Western Europe also contribute over 1 million YLDs to the global total.

The mean age at incidence of angina in the East Asia/Pacific region is 55.3 years, and mean age at incident AMI is 63.7 years. Oceania has notably earlier onset of disease than other regions in this grouping, with onset of angina at 52.6 and incident AMI at 60.7, compared with 57.5 and 67.5 years, respectively, in East Asia. The incidence rate of angina per 100,000 persons is 19.4 in males and 13.3 in females, and for AMI 179.5 and 103.3 per 100,000 males and females, respectively, both small improvements from the two previous decades. Oceania has nearly double the incident rate of AMI in males and females compared with East Asia: 212 versus 132 per 100,000 males and 130 versus 78 per 100,000 females. The prevalence of ischemic cardiomyopathy has increased in this region as well, from 2.3 to 2.7 and 2.1 to 2.3 per 1000 males and females, respectively. Again, Oceania has a markedly worse burden of disease per population than other regions in this grouping, with 5.22 per 1000 males and 4.53 per 1000 females affected by ischemic cardiomyopathy, compared with 1.19 and 0.83, respectively, in East Asia.

As a superregion, East Asia/Pacific has experienced a 70.9% increase in total DALYs secondary to IHD, which is second only to the South Asia superregion. Despite increases in actual DALYs across the board as a superregion, each region has been affected by different dynamics to arrive at a similar point. East Asia, including China, has seen an increase in actual DALYs by 75.5%, of which 47.1% can be attributed to aging of the population and 11.4% to an increase in age-adjusted DALY rates. Only 17% of this increase is the result of population growth, which coupled with a large effect due to aging can likely be linked to the one-child policy pursued in China over the past three decades. In contrast, Southeast Asia, which has seen a reduction in age-adjusted DALY rates by 16%, nevertheless saw actual disease burden increase by 61.5% due to both aging (44.4%) and population growth (33.2%). Oceania has unfortunately seen a 72.3% increase in actual disease burden due to population growth (31.6%), population aging (29.9%), and an increased age-adjusted DALY rate (10.9%).

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