25 by 25: Achieving Global Reduction in Cardiovascular Mortality

Abstract

Four non-communicable diseases—cardiovascular disease, chronic respiratory disease, diabetes mellitus, and cancer— account for over 60 % of all deaths globally. In recognition of this significant epidemic, the United Nations set forth a target of reducing the four major NCDs by 25 % by 2025. Cardiovascular disease alone represents half of these deaths and is the leading cause of death globally, representing as much as 60 % of all deaths in regions such as Eastern Europe. In response, the WHO set specific targets on conditions and risk factors and changes in the health systems structure in order to achieve the goals. The focus was set on lifestyle risk factors—physical activity, salt-intake, and tobacco—and established conditions—obesity, hypertension, and diabetes mellitus. Health system efforts to improve medical treatment of high risk are encouraged. Efforts to achieve the goal are being promoted by leading international CVD organizations.

Introduction

Non-communicable diseases (NCDs)—which comprise cardiovascular disease (CVD), cancer, chronic respiratory diseases, and diabetes—are responsible for a significant proportion of global morbidity and mortality. In 1990, NCDs were responsible for 57 % of global mortality, and by 2010, this increased to 65 % of global mortality. In 2008, of the 57 million deaths globally, 36 million were due to NCDs [1], with up to 80 % of those occurring in low- and middle-income countries (LMICs). Surprisingly, a significant number of deaths in LMICs occur before the age of 60 years, resulting in substantial loss of human, economic, and financial resources, the latter of which is projected to reach US$21 trillion over the next 15 years [2]. In health care costs alone, four conditions, chronic obstructive lung disease, cancer, CVD, and mental health will cost nearly US$47 trillion of which 40 % of that will be attributed to CVD [3].

The growing epidemic of NCDs has been recognized for several years but the efforts to coalesce international attention to the problem have been more recent. Approximately 15 years ago, the World Health Organization (WHO) released a global strategy for the prevention and control of NCDs [4]. Despite this, targets to curb the rise in NCDs were not explicitly outlined in the United Nations Millennium Development Goals [5]. Instead, over the next decade, several regional initiatives were launched to tackle the NCD epidemic locally [6]. In 2008, in a major step forward, 160 parties worldwide ratified the WHO Framework Convention on Tobacco Control [7], making it one of the most successful treaties in the United Nations’ history to tackle a major risk factor for all NCDs. In the same year, the WHO released their 2008–2013 Action Plan on the prevention and control of NCDs [8]. These initiatives from the UN, WHO, and regional organizations culminated in a high-level meeting of the UN General Assembly in September 2011 where the prevention and control of NCDs were discussed. Of the previous 23 meetings convened by the United Nations, this was only the second health-related meeting, with the first one, almost a decade prior, focused on the human immunodeficiency virus (HIV) epidemic. In quick succession 8 months later, the 65th World Health Assembly adopted a resolution to reach a ‘global target of 25 % reduction in premature mortality from noncommunicable diseases such as cardiovascular disease, cancer, diabetes and chronic respiratory diseases by 2025’ [9]. This historic resolution was adopted by all 194 member countries, highlighting the shared burden faced by all nations. A month later, the Rio+20 UN Conference on Sustainable Development acknowledged that the global burden of NCDs is one of the major challenges of the twenty-first century [10, 11]. These major initiatives have led to the widespread adoption of the slogan ‘25 by 25’, reflecting a commitment to a 25 % reduction in NCD mortality by the year 2025 and reminiscent of the ‘3 by 5’ AIDS initiative that aimed to treat 3 million people by the year 2005. Several groups have advocated for the inclusion of NCDs in the 2015 Sustainable Development Goals (SDGs), which describe the post-MDG development agenda [11, 12•, 13].

In recognition of the rising burden of NCDs faced largely by LMICs, the UN SDGs, scheduled to be ratified in the fall of 2015, have included targets towards reducing the number of deaths due to NCDs. In parallel, in 2013, the Global CVD Taskforce brought together leading organizations to address the goals including the World Heart Federation, the American Heart Association, the American College of Cardiology, the European Society of Cardiology, and European Heart Network, which has committed to a 25 % reduction in cardiovascular mortality by the year 2025.

Ultimately, the WHO set voluntary targets for six risk factors and two health services goals in order to achieve the 25% reduction in NCD premature mortality. The six risk factor goals for reduction are as follows: hypertension prevalence by 25 %, tobacco use by 30 %, sodium intake by 30 %, physical inactivity by 10 %, and harmful alcohol use by 10 %. The two health systems based goals include essential medicines and technologies coverage of 80 %, and drug therapy and counseling for 50 % of the population.

Of all the non-communicable diseases, CVD accounts for the largest fraction of deaths and will be the focus of this review. Specifically, we will describe strategies that have resulted in reducing CVD deaths in high-income countries (HICs) and how these strategies might be implemented in LMICs to achieve similar success. We will conclude with describing the unfinished agenda in reducing CVD mortality in LMICs.

Global Burden of Cardiovascular Disease

The World Bank has divided the world into seven regions: one region consisting of HICs and six geographic regions consisting of LMICs. Data on cardiovascular mortality comes largely from the Global Burden of Disease study, which analyzed trends in morbidity and mortality from 187 countries. In 2013, there were more than 17.3 million CVD-related deaths, which represented a 41 % increase over the prior 3 decades, despite a 39% decrease in age-specific death rates [14••]. This increase in CVD deaths has been attributed to a 55 % increase in mortality due to aging populations and a 25 % increase in mortality due to population growth [14••]. A significant proportion of global CVD is driven by deaths among 85 % of the global population residing in LMICs. The burden of deaths due to CVD is shared unequally; while many HIC and Latin American countries have shown age-adjusted declines, only Western Europe and Central Europe have demonstrated an actual decline in the number of CVD deaths whereas the rest of the world has shown an increase [14••].

Success in reducing the number of cardiovascular deaths relies on effective interventions for primary and secondary prevention of cardiovascular disease. Primary prevention depends on the optimal management of cardiovascular risk factors, notably tobacco use, excessive alcohol use, diet and salt intake, and physical activity. Secondary prevention depends on several factors including access to hospital and appropriate therapies, prescription of established secondary prevention medications, and continued medical care. Interventions to improve primary and secondary prevention have focused on the individual—and population—levels, as described below. Success of each of these strategies both in HIC and LMIC have been described in detail before [15•] and briefly reviewed below.

Reduction in CVD Mortality in High-Income Countries

The HICs are divided into four subregions—Australasia, Asia-Pacific, Western Europe, and North America—and have a combined population of 1 billion. As described above, CVD-related deaths have shown different trends in different high-income countries. To understand the trend of cardiovascular deaths in the USA, Ford and colleagues used a statistical model to assess the relative contribution of cardiac treatments and changes in risk factors in reducing the burden of CVD [16]. Compared to deaths 2 decades prior, in 2000, there were approximately 340,000 fewer deaths, of which 44 % were attributed to reduction in management of risk factors (reduction in total cholesterol, systolic blood pressure, smoking prevalence, and physical inactivity) and 47 % were attributed to acute management and secondary prevention (improved revascularization, treatment for acute myocardial infarction and heart failure, and other treatments) [17]. In addition to improved therapies, the development of coronary care units, where patients with high cardiovascular acuity could be monitored and managed also contributed to the reduction in cardiovascular mortality [18]. Similarly, there has been a 50–80% decline in CVD mortality in most high-income countries including Canada, UK, Scotland, Sweden, and New Zealand [19]. As seen in the USA, the 40–75 % of the reduction in mortality in other high-income countries can be attributed to changes in risk factors and 25–50 % can be attributed to more effective treatments [19].

Reduction in CVD Mortality in Low- and Middle-Income Countries

The major burden of cardiovascular morbidity and mortality is concentrated in LMICs. Therefore, efforts to reduce the global burden of CVD will likely require efforts that address root causes of CVD and its risk factors, particularly the lifestyle interventions that affect major risk factors. However, the management of those with current high levels of risk, including those with established CVD will need equal attention. Given the relatively short time frame to meet the 2025 goal, efforts will have to include both population-based strategies as well as strengthening health services for the delivery of primary and secondary prevention as well as acute management.

The World Bank has established six regions of LMICs: East Asia and the Pacific, Central and Eastern Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, South Asia Region, and Sub-Saharan Africa. The GBD study showed that over the past 3 decades, the South Asia Region has had the largest increase in CVD deaths with 1.7 million more deaths in 2013 than in 1990, representing a 97 % increase. East Asia registered a 47 % increase over the same time period [14••].

Risk Factors

As seen in HICs, several interventions in LMICs have aimed to reduce the burden of CVD risk factors and to improve CVD treatments. Approximately 82 % of the 1.1 billion smokers reside in LMICs [20] and by 2030, approximately 10 million deaths annually will be attributed to smoking. Mortality among cigarette smokers is 2–3-fold higher than similarly aged non-smokers [21]. Further, other forms of tobacco including bidis, kreteks, and second-hand smoke are associated with increased CVD mortality [22–27]. To curb the use of tobacco products, tobacco taxation remains the most cost-effective anti-smoking intervention [28, 29]; however, strong political opposition has remained a major barrier to wider implementation. In addition to increasing taxes on tobacco, other strategies that may be successful in reducing tobacco use include public advertisements, legislation to ban smoking in public places [30, 31], and pictorial warnings on tobacco products, which has been successful in both high-income and middle-income countries [32, 33].

In addition to smoking, regulation of dietary salt and fat remains an important target to manage deaths due to cardiovascular disease. The association between salt intake and cardiovascular mortality is conflicting [34, 35]. The World Health Organization recommends sodium consumption of less than 2 g per day or salt consumption of less than 5 g per day [36]. Analysis of sodium intake in 187 countries shows that from 1990 to 2010, the average intake was 3.95 g per day [37]. In addition to salt intake, dietary fat is associated with increased coronary heart disease risk in women [38] and a 2 % increase in energy intake from trans-fatty acids is associated with a 23 % increase in incidence of cardiovascular disease [39]. In general, efforts to reduce dietary salt involve collaboration with the food industry, implementation of government policies, and increase in salt-taxes. There are relatively few studies on this topic in LMICs, and most data comes from HICs. In the UK, industries voluntarily reduced the salt content of food and the average daily salt consumption decreased from 9.6 to 8.6 g (www.food.gov.uk) [40]. Modeling work across 23 countries shows that reducing salt content by 15 % and smoking prevalence by 20 % over a 10-year period could avert 8.5 million and 3.1 million cardiovascular deaths, respectively [41]. This supports other work that reducing salt intake could result in a significant decline in cardiovascular events and medical costs [42, 43].

Many middle-income countries have adopted interventions to reduce physical inactivity as well. Most countries follow the recommendation of the 1996 US Surgeon General to perform at least 30 min of moderate-intensity physical activity on most days of the week [44]. However, to date, fewer interventions have been implemented in low-income countries and very few middle- or low-income countries have actually evaluated the outcomes of their physical activity interventions. This is clearly an area where additional study is needed. Regardless, adopting physical activity interventions is likely to be a cost-effective intervention: a voluntary program to increase walking in the USA in which 25 % of the sedentary population complies with the program would generate US$6.8 billion in savings (in 2001 US dollars) [45].

Efforts to prevent diabetes have centered on lifestyle interventions. Most of these interventions involve both changes in diet and physical activity. Four of the largest trials in this area have shown that such interventions can delay or even prevent diabetes in a high-risk population [46–49]. Trials have also been conducted to assess the efficacy of pharmacologic treatments in the prevention of diabetes; while many of these have shown a decreased incidence of diabetes, the cost, side effects, and other logistical concerns of implementing such interventions on a large scale are significant [50].

In terms of treatment of people with established diabetes, Venkat Narayan et al. assessed three interventions to be both cost-saving and feasible: glycemic control in people with HbA1c greater than 9 %, blood pressure control in people with blood pressure greater than 160/95 mmHg, and foot care in people with high risk of foot ulcers [50]. All of these, however, require a health infrastructure in which diabetics has affordable access to care as well as availability of effective, inexpensive drugs.

The risk factor that was missing from the WHO targets that is most glaring is an effort to address lipid levels. There will certainly be some change in lipid levels if there are improvements in physical activity and reductions in obesity levels. Certainly, some of the reductions in cholesterol levels that have occurred in both HIC and LMICs over the last 30 years [51] is a result of some of the lifestyle changes that have occurred. However, much of the reductions particularly over the last 20 years have been since the introduction of the statin medications. While this may be addressed in part with the attention placed on increasing coverage for essential medications, by not addressing it directly there may be some loss of opportunity, particularly since simvastatin was only recently added to the WHO essential medication list and several other statins remain off the list.

Health System Challenges

A clear barrier to the prevention and treatment of cardiovascular disease in developing countries is the lack of essential medications. Investigators from the WHO conducted a survey of 32 medications used to treat chronic diseases in six LMICs (Bangladesh, Malawi, Nepal, Brazil, Pakistan, and Sri Lanka) [52]. The study found that availability of cardiovascular medications was poor in the public sector, forcing patients to either purchase medicines in the more costly private sector or to forgo treatment altogether. Cameron et al. found that in 40 LMICs, generic medications for communicable diseases were significantly more available than those for non-communicable diseases in both the public sector (53.5 % availability vs. 36.0 %) and the private sector (66.2 % availability vs. 54.7 %) [53].

Equally as striking is the low level of affordability of these drugs in developing countries. The study by Mendis et al. found that 1 month of combination therapy with the lowest-priced generic version of aspirin, a statin, a beta-blocker, and an ACEI cost 1.5 days’ wages of the lowest-level government worker in Sri Lanka; more than 5 days’ wages in Brazil, Nepal, and Pakistan; and more than 18 days’ wages in Malawi [52]. The lack of availability and affordability of cardiovascular medicines was confirmed in a 2010 study. Investigators conducted a survey of five anti-hypertensive medications in 36 countries with different socioeconomic status [54]. They showed that the overall availability of cardiovascular medicines was poor (mean 26.3 % in public sector for lowest-priced generic, 57.3 % in private sector) and that buying a brand product cost 4.2 times as much as buying the lowest-priced generic. This finding highlights the important role that generic drugs play in treating illness in poorer nations.

Acute Management

The use of the CCU is cost-effective when triage to the highest-risk patients is appropriately applied [55, 56]. Aspirin and beta-blocker usage for ACS ranges from 75–95 % in middle-income countries [57]. Further, it has been shown to be highly cost-effective in this setting, costing less than $25/QALY gained [58]. The use of thrombolytic therapy for AMI varies by LMIC region. Though this therapy is used more commonly than PCI in countries with low GNI, the time to initiation of thrombolytic therapy is longer than in their high GNI counterparts (4.3 vs. 2.8 h) [57] leading to a reduction in its effectiveness. Nonetheless, thrombolysis with streptokinase (the most commonly used and least expensive agent) [59] has been shown to be cost-effective in developing nations according to WHO’s standards [58, 60].

As of 2002, the majority of patients with acute coronary syndromes in multiple regions of the world did not undergo any type of revascularization procedure. Rates of PCI were highest in the USA and were particularly low in Eastern Europe [61, 62]. Unsurprisingly, PCI use was significantly associated with GNI, as only 1.3 % of ACS patients in low GNI countries received PCI compared with 22.7%of ACS patients in high GNI countries [57]. As with CABG, efforts to implement PCI can be cost-effective in HI countries, but less is known about whether the same holds true for LMIC.

Conclusions

High-income countries have seen on average 2–5 % reductions in age-adjusted CVD mortality over the last 40 years fairly consistently. Therefore, a goal of 25 % reduction for the next 10 years is achievable provided appropriate attention and resources are focused on the challenge. The targets set by the WHO regarding risk factors are reasonable in most cases and serve as an appropriate starting point. Certainly targeting tobacco control and hypertension through reduced salt intake, increased physical activity and improved diet will be important key features of the global effort. However, additional focus on management of lipids with the use of statins should be more clearly targeted as well. Efforts to improve acute management of those with acute ischemic heart disease should parallel the great preventive efforts ongoing at the policy level as well. To mirror the success of the prior 50 years will require efforts focused at the national or international level as well as at the individual patient.