Cardiovascular disease (CVD) is the number one cause of death in both sexes and in all races and ethnicities throughout the world today . Contrary to popular myth, CVD is of greater burden in the developing countries (countries with developing economies) than it is in developed countries (countries with advanced, industrial economies) [2, 3] (Figure 1). The understanding of CVD as a global phenomenon is a relatively new concept. Much of the CVD research in the developing world in the early and mid-20th century focused on answering the question of why patients in these countries seemed to be shielded from the effects of CVD . A vast majority of relief efforts and charitable contributions to developing countries are allocated towards the prevention of nutritional disorders and infectious diseases, with a relative sparsity of funding for prevention and treatment of CVD [2, 5, 6].
The burden of CVD in the developing countries has risen dramatically in the last 50 years, and is anticipated to continue to rise [1, 7]. This increase in CVD burden has been driven by two important factors. The first is “modernization” of the developing world, which has led to increased exposure to known risk factors for CVD (unhealthy diet, sedentary lifestyle, and tobacco). The second is a demographic age shift known as the “modern epidemiological transition.” Efforts to combat nutritional, perinatal, and infectious diseases in the developing world have allowed many more patients to survive to middle and old age, increasing the number of patients at risk for CVD. Patients who are no longer dying from infectious disease or starvation are now living long enough to develop CVD and its complications [1, 8–10].
CVD places an extremely large burden on both individual and public health, as well as the global economy. Patients afflicted with CVD are in general younger in the developing world than in the developed world, creating a deficit in the available work force which hurts both the local and global economies [11, 12]. In response to these concerns, large international organizations such as the World Health Organization (WHO) and World Heart Federation (WHF) have made formal recommendations to help combat the problem of CVD in the developing world [1, 13]. Two key components of CVD, atherosclerosis and hypertensive heart disease, develop slowly over time and in response to modifiable risk factors, presenting an opportunity to implement changes that may decrease the burden of CVD [11, 14].
Perspectives on the global burden of CVD have evolved over the last 100 years. As knowledge of the pathogenesis of atherosclerosis and hypertensive heart disease has blossomed, so has the understanding of the true epidemiological burden of heart disease. Once thought to be a disease not prevalent in the developing world, CVD is now known to be the number one cause of death worldwide . Indeed, atherosclerotic CVD and hypertensive heart disease claim more lives, account for more disability, and result in a greater economic burden in the developing world than in the developed world [2, 3, 11]. The potential health and economic impacts of CVD in the developing world are enormous, and appropriate action is necessary to thwart the ever-growing problem .
In the early 20th century, many scientists thought CVD to be a malady of “civilization” that would not be found in the developing world. Donnison observed very little cardiovascular pathology during his time studying near Lake Victoria in Kenya in the 1920s. He wrote, “The results of this investigation thus lend support to the view that hyperpiesia (essential hypertension) and arteriosclerosis are diseases associated with civilization” . The model of a transition from the infectious diseases of poverty to degenerative diseases of affluence framed the problem of heart disease in the developing world at that time.
Understanding of CVD and its importance in Africa, Asia, and Latin America began to change in the 1940s and 1950s. By the end of World War II, the importance of heart disease in these regions had come into greater focus . By the late 1950s, heart failure was responsible for a significant proportion of admissions in sub-Saharan Africa .
In the 1960s, Miller and Spencer spent 6 months studying cardiovascular pathology in the Gabonese Republic “To discover… that three quarters of the inpatients and outpatients have definite evidence of one or more cardiovascular diseases was indeed unexpected,” they wrote. “The high prevalence of mitral stenosis is astonishing. With our present knowledge of the cause and surgical relief of rheumatic heart disease, we believe strongly that it is a duty to help bring to these sufferers the benefits of better penicillin prophylaxis and of cardiac surgery when indicated.” They summarized their plea for recognition of the problem by writing, “We hope, however, that this report may increase the reader’s awareness of our opportunity and obligation to share more generously the life-saving measures of modern medical science with those elsewhere who need so much and have so little” .
Some initiatives, such as penicillin prophylaxis for rheumatic heart disease, continued through this period. However this call for action had little impact on an audience preoccupied with investigating the problem of CVD in the developed world. Investigations into the true burden and impact of CVD in the developing world were lacking. Scientific endeavors in the developing world were not aimed at control of heart disease but rather at explaining what protected those populations from acquiring the atherosclerotic pathologies common in Europe and North America .
In contast to their counterparts in the developed world, healthcare leaders in several developing countries not only recognized a growing problem but called for increasing prevention measures as early as the 1960s. Leaders in West and East Africa fought to put CVD on the global agenda [18–20]. Dr. Hilary Ojiambo attacked the notion “that heart diseases are diseases of ‘civilization’ and do not warrant attention in the developing world.” He argued that not only were cardiovascular diseases accounting for 10% of admissions in East and Central Africa, but also that “these are the diseases of tomorrow” . Paul D’Arbela of Uganda wrote in 1975 that the problem in Uganda was no longer why hypertension was so rare, but rather why it was so prominent . Similarly, J.O.M. Pobee wrote that in Ghana “Cardiovascular disease and its major risk factors such as hypertension undoubtedly compete with other conditions such as malaria … for limited resources. However, ignoring the need to institute effective prevention strategies now will certainly result in greater burden with increased challenges in the near future” .
By the mid-1970s the rising problem of CVD in the developing world began to receive attention by certain world organizations, including the World Health Organization (WHO), a specialized agency of the United Nations that is concerned with international public health. In his 1974 introduction to a volume on tropical cardiology, Fejfar wrote: “Ischemic heart disease with coronary atherosclerosis as the underlying cause, is associated with affluence in the industrialized, socio-economically advanced society. In the so-called developing world the growth of a similar type of society is increasing the menace of ischemic heart disease becoming the world’s largest epidemic of this century, unless we can find a way of controlling and reversing the present trend” . By 1988 the WHO declared, “Heart attacks are developing in the developing world” .
Meanwhile, the understanding of coronary disease epidemiology and treatment in the developed world made great strides. Important risk factors for coronary disease were discovered , and mortality and morbidity from coronary events declined, mostly due to improvements in coronary care [23, 24].
By the late 20th Century, the scientific community had established the burden of cardiovascular disease as a global phenomenon, the major risk factors playing a critical role in pathogenesis , and proven treatment strategies which could lead to a decrease in mortality and morbidity [23, 24]. Despite this recognition, most public health attention and funding in the developing world went to treatment and prevention of communicable diseases. Initiatives against polio, small pox, malaria, and HIV/AIDS dominated global spending and health programs in the developing world throughout most of the 20th century [5, 6].
Meanwhile, only a small amount of international assistance went to cardiovascular disease control. For example, Yach et al. found that by 2002, only 0.1% of the $2.9 billion in global aid for overseas health sector development went to chronic diseases of any kind .
Current Understanding of the Global Burden of CVD
The health of populations throughout the world is seriously compromised by the ubiquitous occurrence of CVD, and CVD is the number one cause of death throughout the world (Figure 2). Prevention and control of CVD and other chronic conditions have now been recognized by the United Nations General Assembly (UNGA) as “one of the major challenges for development in the twenty-first century” . At present, the developing countries contribute a greater share to the global burden of CVD than the developed countries [2, 3, 11] (Figure 3). The two most important diseases which have been projected for the year 2020 to rank first and second in frequency among causes of death are the atherosclerotic and hypertensive diseases .
CVD creates a high burden of mortality and morbidity across all races and ethnicities, and CVD deaths occur almost equally in men and women. An estimated 17.5 million people died from CVD in 2012, representing 31% of all global deaths (Figure 3) . Most of these deaths, over 80% by some estimates, take place in low- and middle-income countries . Although the present high burden of CVD deaths is in itself an adequate reason for attention, a greater cause for concern is the early age of CVD deaths in the developing countries. For example, in 1990, the proportion of CVD mortalities occurring below the age of 70 years was 26.5% in the developed countries compared with 46.7% in the developing countries .
In 2004, A Race Against Time projected a devastating impact of CVD specifically on the working-age populations (ages 35–64 years) of low- and middle-income countries by the year 2030: “...Without concerted, ongoing intervention to prevent the precursors and reverse the negative effects of CVD in developing countries, a global health crisis in the current workforces (and later among the elderly) of those countries will occur – and sooner, rather than later” . Recent data proves that CVD places a substantial burden on national economies. For example, in China annual direct costs accrued from CVD are estimated at more than $40 billion (4% of gross national income) .
Why is the Rate of CVD Increasing in the Developing World?
CVD places a large healthcare and economic burden on developing countries, with potentially devastating consequences. To understand how to combat this problem, one must understand the forces driving the increase in CVD. The two main forces responsible are urbanization and the modern epidemiological transition.
The World Heart Federation (WHF) argues that urbanization in the developing world is largely responsible for the rise in CVD. They note that only 10% of the population lived in cities in 1900, whereas 50% of the world’s population lives in an urban setting today, and it is estimated that this proportion will reach 75% by 2050. Urbanization leads to unhealthy lifestyles through greater exposure to advertisements for tobacco and alcohol, greater access to high salt/high fat content in food, and increased spread of communicable diseases and rheumatic heart disease .
Urbanization also leads to less physical activity and unhealthier diets. The lack of physical activity is fostered by public transportation and lack of “green spaces” in modern cities. Urbanization encourages a shift from traditional cooking to ready-prepared and processed foods that are often high in calories, salt, and fat content. Gaining calories from sugar and fat has become easier and cheaper than gaining calories from vegetables or fruit. Unhealthy lifestyles often begin early in life, and the WHF estimates that there are currently 35 million overweight children living in developing countries .
Finally, urbanization affects tobacco use through more exposure to tobacco advertising and easier access to tobacco products . Recent projections from the WHO suggest that, by the year 2020, tobacco use will account for 12.3% of global deaths. A large component of this will be in the form of CVD deaths. In India alone, the tobacco attributable toll is projected to rise from 1.4% in 1990 to 13.3% in 2020. “Tobacco is the leading avoidable cause of death worldwide and its rising consumption in the developing countries warrants early and effective public health responses” . Smoking directly causes 1/10 of CVD worldwide . The risk of non-fatal MI increases by 5.6% for every daily cigarette smoked , and chewing tobacco doubles the risk of having an MI . Awareness of tobacco hazards has matured over the last 50 years in the developed world; however, awareness of tobacco hazards in the developing world may be lower than expected. In one survey of smokers in China, 70% were unaware that smoking increased their risk for stroke . This deficiency in knowledge leads to an opportunity for intervention via education. Indeed, smoking bans have decreased the rates of heart attacks . Quitting smoking has been proven to have a multitude of positive effects. If a patient quits smoking: 20 min later blood pressure and pulse return to normal , 5 years later the risk of MI is half that of a smoker , and 15 years later the risk of CVD is similar to that of a non-smoker .
The hypothesis that urbanization leads to greater CVD was born out in a cross-sectional survey of urban Delhi and its rural surroundings. The investigators found a higher prevalence of CVD in the urban sample when compared to their rural counterparts. They additionally noted higher body mass index, blood pressure, fasting lipids (total cholesterol, ratio of cholesterol to HDL cholesterol, triglycerides), and prevalence of diabetes .
Modern Epidemiological Transition
The second reason for the rise in CVD mortality in the developing world is known as the modern epidemiological transition. In the second half of the 20th century, most developing countries saw a rise in life expectancy related to efforts to combat perinatal, nutritional, and infectious disorders. This resulted in more children living to adulthood and thus higher numbers of middle aged and older adults. This decline in deaths from infectious causes and rise in deaths from chronic diseases is referred to as the Modern Epidemiological Transition [27, 34]. As the number of deaths from infectious, perinatal, and nutritional disorders declined, the number of deaths from NCDs (chiefly CVD) increased. In urban China the proportion of CVD deaths rose from 12.1% in 1957 to 35.8% in 1990 .
CVD mortality is expected to increase based on both the increasing age of populations in the developing world as well as the urbanization and subsequent rise in risk factor exposure in the developing world. The demographic age shift in developing societies alone will result in an anticipated rise in CVD mortality. Because urbanization contributes to increased risk factor exposure, the rise in CVD mortality may even be larger than these estimates based solely on demographic shifts.
Medical and Economic Sequale of CVD
The medical and economic sequelae of this projected increase in CVD could prove disastrous for developing countries for multiple reasons. Health care facilities required for clinical evaluation and management of the many millions of CVD patients is beyond the scope of most developing countries. Death or disability in the productive years of life will decrease the number of able-bodied workers and thus have an effect on economic productivity in addition to affecting individuals, families, and society as a whole. Nations that must invest their resources in programs of industrial growth and sustainable development may not be able to afford the escalated health care costs brought on by the management of CVD. Expensive interventions and costly drugs may not be available, accessible, or affordable, except for an elite minority.
While the treatment of CVD can prove cumbersome and expensive, the prevention of CVD is often lifestyle based and extremely cost-effective. Thus, efforts to combat CVD burden may be best aimed at prevention of CVD through risk factor modification .
Risk Factors for CVD in the Developing World
Are the risk factors that we know play a role in cardiovascular disease in the developed world generalizable to the developing world? Two studies examined this question, aiming to elucidate the truth regarding CVD developing world.
The INTERHEART Study of factors associated with myocardial infarction in 52 countries throughout the world demonstrated that nine factors accounted for >90% of the risk of myocardial infarction among men and women in these populations .
Risk factors for myocardial infarction worldwide, in both sexes, and at all ages:
Decreased consumption of fruits and vegetables
Increased consumption of alcohol
Lack of regular physical activity 
The Global Burden of Disease Study demonstrated that the commonly recognized risk factors jointly account for 80% of the burden of ischemic heart disease in both the developing and the developed world . Therefore approaches to prevention can be based on similar principles worldwide. Intervention upon these often modifiable risk factors has the potential to prevent most premature cases of myocardial infarction.
The Case for Intervention
The case for intervention can be made based on both the knowledge that CVD has severe human and economic impacts . A series of reports in the Lancet in 2007 estimated that cost-effective interventions in developing countries with a high burden of CVD could lead to an estimated 24 million lives saved. This reduction in CVD mortality rate would reduce economic costs by $8 billion. Investments in health would reduce the burden of disease, increase the number of able bodied workers, and stimulate economic growth .
There are two main goals for intervention in the developing world: cardiovascular health (CVH) promotion and CVD prevention. CVH Promotion is defined as avoidance of risk factors and maintenance of ideal CVH, whereas CVD prevention is defined as reducing risk factors once present, treating critical CVD events and managing their consequences .
Two areas for intervention include modification in high risk individuals as well as a population-wide approach. Targeting high-risk individuals only reaches a small proportion of the population. The population-wide approach reduces risk where the majority of CVD events occur: levels of risk above optimum but not extreme .
WHO Action Plan
In 2008, the WHO released a Draft Action Plan for the Global Strategy for the Prevention and Control of Non-communicable Diseases. “The epidemic of these diseases is being driven by powerful forces now touching every region of the world: demographic ageing, rapid unplanned urbanization, and the globalization of unhealthy lifestyles. While many chronic conditions develop slowly, changes in lifestyles and behaviors are occurring with a stunning speed and sweep.” The action plan aimed to reduce the level of exposure to the common modifiable risk factors for NCDs, called for a strengthening of healthcare systems with a focus on chronic disease, and supported programs to increase the capacity of individuals and populations to make healthier lifestyle choices .
The WHO proposed both population-wide and individual healthcare interventions to be undertaken immediately “to produce accelerated results in terms of lives saved, diseases prevented and heavy costs avoided.” Their aims included targeting entire populations early in life- to both promote ideal CVH and prevent the development of CVD. They called for multi-sectoral action from the government, civil society, and the private sector. They endorsed surveillance and monitoring of specific, measurable, world-wide indicators of CVH, as well as strengthening of healthcare systems through innovative financing, increasing efficiency, and focusing on primary care. They called on civil society and the private sector to take responsible corporate actions such as product reformulation and more desirable marketing approaches .
WHO Action Items
Finally, the WHO released a group of action items (termed “Best Buys”), on both a population and individual level, that would be cost-effective in reducing the burden of CVD.
The “best buys” on the population level were:
Banning smoking from public places
Warning about the dangers of tobacco smoke
Enforcing bans on tobacco advertising, promotion, and sponsorship
Raising taxes on tobacco
Restricting access to retailed alcohol
Enforcing bans on alcohol advertising
Raising taxes on alcohol
Reducing salt intake and salt content of food
Replacing trans fat with polyunsaturated fat
The individual level “best buys” included promoting awareness about diet and exercise as well as counseling and a “multi-drug therapy” (aspirin, statin, and an anti-hypertensive) for those individuals at a high risk of CVD. The final “best buy” on the individual level was aspirin therapy for MI . Other interventions on an individual level may be strongly supported but currently lack data for cost effectiveness .
World Heart Federation Strategy
The WHF has also released a strategy for change and summarized by the acronymic SPACE strategy :
Stakeholder collaboration: inclusion of all government sectors, the private sector and civil society
Planning cities: develop infrastructures that facilitate proper cardiovascular behavior
Access to healthcare: ensure that the health needs of all members of society are included regardless of economic income
Child-focused dialogue: discussions around CVD must focus on children specifically
Evaluation: evaluate which city dwellers face which barriers to proper healthy living and why
The current goals of CVD disease prevention heralded by the WHO and the WHF focus on primary prevention and are for the most part non-pharmacological, population based, and lifestyle linked. Some criticize this approach. Reddy et al questioned the utility of “messages of moderation” and their receptiveness (or lack thereof) in developing countries, noting it may be difficult to ask individuals who may have grown up in poverty and now have access to excess to refrain from overindulgence. They also called for a more robust response to manifest disease and suitable algorithms for early diagnosis. They state that low cost life-saving interventions (e.g., aspirin) must be readily available .
Call to Action by Nursing Leaders
Nursing leaders have also formulated a “Call to Action” for global CVD prevention involvement by nurses. The Journal of Cardiovascular Nursing in July–August 2011 published multiple possible approaches. These included nurse-led primary or secondary prevention programs, capacity building (defined as preparing nurses to assume leadership roles in CVD prevention), and community-based programs for primary prevention and promotion of CVH .
The knowledge of CVD as a global phenomenon has expanded rapidly over the last century. CVD is the number one cause of mortality world-wide and places a high medical and socioeconomic burden on developing countries. The burden of CVD has increased over the last one hundred years due to rapid urbanization and the demographic shift known as the modern epidemiologic transition. The two chief contributors to CVD, atherosclerosis and hypertensive heart disease develop slowly over time and often in response to risk factor exposures which are modifiable, presenting an opportunity for prevention.