Global Burden of Cardiovascular Disease

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Shifting Burden

Between 1990 and 2017, deaths from cardiovascular disease (CVD) increased from 26% to 32% of all deaths globally, a reflection of the rapid epidemiologic transition, particularly in low- and middle-income countries (LMICs). Although the net percentage of deaths caused by CVD overall has increased, this reflects a rise in LMICs and a decline in high-income countries (HICs) ( Fig. 2.1 ). CVD now causes most deaths in all low- and middle-income regions, with the exception of sub-Saharan Africa, where it is the second leading cause of death overall, and the leading cause in those 50 years and older. In absolute numbers, five times as many CVD deaths occurred in the low- and middle-income regions combined than in the High-Income region in 2017 (14.8 million to 3 million). Within the six World Bank–defined low- and middle-income regions, the CVD burden differs vastly ( Fig. 2.2 ), with CVD deaths accounting for as much as 43.7% of all deaths in Europe and Central Asia and as little as 12.3% in sub-Saharan Africa. Cardiovascular disease accounts for 31.8% of deaths in HICs.

Epidemiologic Transitions

The overall increase in the global burden of CVD and the distinct regional patterns result in part from the “epidemiologic transition,” which includes four basic stages ( Table 2.1 ): Pestilence and Famine, Receding Pandemics, Degenerative and Man-Made Diseases, and Delayed Degenerative Diseases. ^, 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 stage of Pestilence and Famine has occurred much later in LMICs, it has also occurred more rapidly, driven largely by the transfer of low-cost agricultural technologies, the overall globalization of world economies, and public health advances.

Humans evolved during the stage of Pestilence and Famine and have lived with epidemics and hunger for most of recorded history. Before 1900, infectious diseases and malnutrition constituted the most common causes of death in virtually every part of the world, with tuberculosis, pneumonia, and diarrheal diseases accounting for a majority of deaths. These conditions, along with high infant and child mortality rates, resulted in a mean life expectancy of approximately 30 years.

Per capita income and life expectancy increased during the stage of Receding Pandemics as the emergence of public health systems, cleaner water supplies, and improved food production and distribution combined to reduce deaths from infectious disease and malnutrition. Improvements in medical education and with other public health changes, contribute to dramatic declines in infectious disease mortality rates. Rheumatic valvular disease, hypertension, and cerebrovascular accident (stroke) cause most CVD. Coronary heart disease (CHD) often occurs at a lower prevalence rate than stroke, and CVD accounts for 10% to 35% of deaths.

During the stage of Degenerative and Man-Made Diseases, continued improvements in economic circumstances, combined with urbanization and radical changes in the nature of work-related activities, led to dramatic changes in diet, activity levels, and behaviors such as smoking. For example, in the United States, deaths from infectious diseases decreased to less than 50 per 100,000 people per year, and life expectancy increased to almost 70 years. The increased availability of foods high in calories, coupled with decreased physical activity, contribute to an increase in atherosclerosis. In this stage, CHD and stroke predominate, and between 35% and 65% of all deaths are related to CVD. Typically, the ratio of CHD to stroke is 2:1 to 3:1.

In the stage of Delayed Degenerative Diseases, CVD and cancer remain the major causes of morbidity and mortality, but CVD age-adjusted mortality rates decline by almost half, accounting for 25% to 40% of all deaths. Two significant advances have contributed to the decline in CVD mortality rates: new therapeutic approaches and prevention measures targeted at people with or at risk for CVD. ^,

Treatments once considered advanced including the establishment of emergency medical systems, coronary care units, and the widespread use of new diagnostic and therapeutic technologies such as echocardiography, cardiac catheterization, percutaneous coronary intervention (PCI), bypass surgery, and implantation of pacemakers and defibrillators have now become the standard of care. Advances in drug development have also yielded major benefits on both acute and chronic outcomes. Efforts to improve the acute management of myocardial infarction (MI) led to the application of lifesaving interventions such as beta-adrenergic blocking agents (beta blockers), PCI, thrombolytics, statins, and angiotensin-converting enzyme (ACE) inhibitors (see Chapter 37, Chapter 38 ). Advances in both heart failure and diabetes management have led to new angiotensin-receptor neprilysin inhibitors, SGLT2 inhibitors, and GLP-1 agonists which reduce cardiovascular events. The widespread use of an “old” drug, aspirin, has also reduced the risk of dying of acute or secondary coronary events. Low-cost pharmacologic treatment for hypertension (see Chapter 26 ) and the development of highly effective cholesterol-lowering drugs such as statins have also made major contributions to both primary and secondary prevention by reducing CVD-related deaths (see Chapter 27 ).

In concert with these advances, public health campaigns have conveyed that certain behaviors increase the risk of CVD and that lifestyle modifications can reduce risk. In this regard, smoking cessation furnishes a model of success. In the United States, for example, 57% of men smoked cigarettes in 1955; in 2018, 15.6% of men smoked. The prevalence of smoking among U.S. women has fallen from 34% in 1965 to 13.7% in 2018. Campaigns from the 1970s dramatically improved the detection and treatment of hypertension in the United States. This intervention likely had an immediate and profound effect on stroke rates and a subtler effect on CHD rates. Public health messages concerning saturated fat and cholesterol had a similar impact on fat consumption and cholesterol levels. Population mean cholesterol levels also declined, from 220 mg/dL in the early 1960s to 191 mg/dL by 2016, with a simultaneous decrease in the prevalence of elevated low-density lipoprotein (LDL) cholesterol.

Different Patterns of Epidemiologic Transition

The HICs have followed different patterns of the CVD transition, which differ in both the peak of death rate from CHD and the time of transition. Three patterns emerge that rely on data from countries with an established death certification system. Countries in Latin America appear to follow the three different patterns as well ( Fig. 2.3 ). One pattern, followed by the United States and Canada, showed a rapid rise and peak in the 1960s and 1970s, followed by a relatively rapid decline through the end of the 2000s. The peak was 300 to 700 CHD deaths per 100,000 population, with current rates between 100 and 200 per 100,000. This pattern also occurred in the Scandinavian countries, the United Kingdom, Ireland, Australia, and New Zealand. In Latin America, Argentina has followed this pattern with a rapid decline from 1985 to 2016 with a CHD-related death rate of 70 per 100,000 at the end of the time period. A second pattern showed a peak in the same period in CHD-related deaths of 100 to 300 per 100,000. Countries such as Portugal, Spain, Italy, France, Greece, and Japan followed this pattern. Some countries did not have the same rapid decline in rate. In central European countries (Austria, Belgium, and Germany), the decline was slower compared to northern European countries (Finland, Sweden, Denmark, and Norway), but had lower peaks of 300 to 350 per 100,000 in the 1960s and 1970s. Colombia appears to follow this pattern with relatively flat to declining levels at 150 deaths per 100,000, with a small decline from 2010 to 2015. Some countries appear to display a third pattern of continued rise (particularly many components of the former Soviet Union), and others have yet to see any significant increase, such as many countries in sub-Saharan Africa (excluding South Africa). Mexico appears to follow this pattern with rates nearly doubling from 80 to 160 per 100,000 from 1985 to 2015. Whether other LMICs will follow a “classic” pattern of significant increases then rapid declines in rates (as happened in North America, Australia, and northwestern European HICs), a more gradual rise and fall (as in southern and central European countries), or some other pattern, will depend in part on cultural differences, secular trends, and responses at the country level with regard to both public health and treatment infrastructures.

Current Variations in the Global Burden

Three phenomena impact the various metrics of disease burden. First, population growth increases the overall number of deaths caused by CVD globally. Second, a trend in general aging of the population has shifted the proportion of deaths caused by CVD in most regions as a result of better control of many communicable diseases that manifest at early stages. Third, prevention of CVD and treatment for those with CVD have both improved, which reduces age-adjusted mortality rates. We rely on data from the Global Burden of Disease (GBD) study data from 2017. Although extensive, data from GBD 2017 have limitations. The availability and reliability of data on the cause of death, especially in LMICs without standardized protocols, are uncertain.

Globally, CVD-related deaths increased by 49% between 1990 and 2017. The increase in overall CVD-related deaths results from both increases in CHD and stroke-related deaths. CHD was the leading cause of death in 2017, accounting for 16% of all deaths worldwide. The second-ranking cause of death was stroke, at 11%. An estimated 15.1 million people died from CHD and stroke, which together accounted for more than a quarter of all deaths worldwide in 2017.

Although still substantial, deaths from communicable, neonatal, and maternal diseases are decreasing worldwide, with a 32.5% decrease between 1990 and 2017. Deaths from noncommunicable diseases increased by 53% in the same period. In 2017, CHD accounted for the largest portion of global years of life lost (YLLs) and the second highest of DALYs. Stroke was the third-ranking contributor to both global YLLs and DALYs. On the other hand, in 1990, communicable diseases accounted for the largest portion of both YLLs and DALYs.

Despite the increase in overall CVD-related deaths, the age-adjusted death rates decreased by 30.4% in the same period, from 335 to 233 per 100,000 population, suggesting significant delays in the age of occurrence and/or improvements in case-fatality rates. Unfortunately, not all countries share in the reductions. Examination of regional trends is helpful in estimating global trends in the burden of disease, particularly CVD. Because 85% of the world’s population lives in LMICs, these countries largely drive global CVD rates. These estimates depend on modeling mortality rates in areas where established death certification–based vital registration systems do not cover the entire country. Even as age-adjusted rates have been falling globally, the pattern is different when assessed by income ( Fig. 2.4 ) or by region ( Fig. 2.5 ).

The magnitude of the peak of the CVD epidemic, and whether the peak has arrived at all, has a great range. Here we describe and highlight trends in the seven regions of the world as defined by the GBD project, which includes HICs as one grouping and divides the remaining LMICs into six geographic regions, further divided by sub-regions: the High-Income, East Asia and Oceania, Central and Eastern Europe and Central Asia, Latin America and Caribbean, Middle East and North Africa, and sub-Saharan Africa regions. All these regions had declines in age-adjusted CVD mortality rates from 1990 to 2017. South Asia had only a slight decrease in its age-adjusted CVD mortality rates.

Much of the variation is related to income, which is one proxy for the stages of the epidemiologic transition. Looking at age-adjusted CVD-related death rates by World Bank, the high-income regions had different trends over the last two and a half decades. In the low-income region, the death rate has decreased from 364 to 285 per 100,000 between 1990 and 2017. The Lower Middle-Income region saw a small increase (368 to 371 per 100,000) between 1990 and 1995, followed by a fall to 317 per 100,000 in 2017. The upper middle-income region saw a 30% decline, from 365 to 254 per 100,000 between 1990 and 2017. The high-income region had a 53% decline, from 272 to 128 CVD deaths per 100,000.

The LMICs have a high degree of heterogeneity with respect to the phase of the epidemiologic transition. First, LMIC sub-regions differ by age-adjusted CVD death rates ( Fig. 2.6 ). Next, low- and middle-income sub-regions are unique, as illustrated by the different CVD disease rates by cause in each region ( Fig. 2.7 ). Lastly, in the East Asia and Oceania region, stroke still exceeds CHD as a cause of CVD-related death. Hypertensive heart disease is the largest single contributor among remaining causes of CVD morbidity and mortality, and sub-Saharan Africa remains the region with the largest contribution from this cause.

Variability in disease prevalence among various regions likely results from multiple factors. First, the countries are in various phases of the epidemiologic transition described earlier. Second, the regions may have cultural and genetic differences that lead to varying levels of CVD risk. For example, per capita consumption of dairy products (and thus consumption of saturated fat) is much higher in India than in China, although it is rising in both countries. Third, certain additional competing pressures exist in some regions, such as war or infectious diseases (HIV/AIDS) in sub-Saharan Africa.

Because CHD affects a younger population in LMICs, the number of deaths is increased in the working population. For some LMICs, the severity of the epidemiologic transition has appeared to follow a reverse social gradient, with members of lower socioeconomic groups having the greatest rates of CHD and the highest levels of various risk factors. Unfortunately, reductions in risk factors do not follow the same trend. Compared with people in the upper and middle socioeconomic strata, those in the lowest stratum are less likely to acquire and apply information on risk factors and behavior modifications or to have access to advanced treatment. Consequently, CVD mortality rates decline later among those of lower socioeconomic status.