The International Pandemic of Chronic Cardiovascular Disease

During the final decades of the 20th century, major medical advances in the prevention and treatment of cardiovascular diseases contributed to declining rates of death from cardiovascular disease.^{1 - 2} Despite these recent reductions in overall cardiovascular death rates in the United States, the overall incidence of acute myocardial infarction (MI) has not declined and has actually increased among women.² Cardiovascular disease remains the leading cause of death worldwide and is a major cause of disability. The epidemic of obesity and associated diabetes is expected to further increase the prevalence of cardiovascular disease in the 21st century.^{3 - 4}

As the ability to increase survival after an acute cardiovascular event improves, greater numbers of men and women will live with chronic, clinically manifest cardiovascular disease. The US Census Bureau estimates that in 2010, 40 million adults will be aged 65 years or older.⁵ Many of these older men and women will live with chronic cardiovascular diseases.⁶ In addition to these challenges, cardiovascular disease is an increasingly global condition: it is the major cause of death in developed countries outside of the United States and is becoming increasingly prevalent in developing countries.⁷ The implications of this large and increasing burden of chronic cardiovascular disease among patients treated in the outpatient clinical setting around the world are not well understood.

In this issue of JAMA, Steg et al⁸ describe 1-year rates of cardiovascular events and hospitalization among 68 236 outpatients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry who were enrolled from physician office practices from 44 countries during 2003-2004. The REACH Registry included patients aged 45 years or older: 55 814 patients with established atherosclerotic arterial disease (coronary artery disease [CAD], peripheral arterial disease [PAD], or cerebrovascular disease [CVD]) and 12 422 patients without established atherosclerotic arterial disease who had 3 or more risk factors for atherosclerotic diseases. Among participants with established atherosclerotic arterial disease, the mortality rate was 2.81% at the 1-year follow-up, and the rate of combined cardiovascular disease death, MI, or stroke was 4.69% at the 1-year follow-up. Among participants with established atherosclerotic disease, the 1-year rate of cardiovascular death, MI, stroke, or hospitalization for revascularization or cardiovascular disease was 14.41%. Thus, approximately 1 in 7 patients with established atherosclerotic disease at baseline either experienced a major cardiovascular event or was hospitalized for revascularization or for a cardiovascular event during the first year of follow-up. These data document an astounding rate of costly and potentially debilitating events among individuals with chronic cardiovascular disease around the world.

The coexistence of clinically evident atherosclerosis in more than 1 arterial bed has been established,^{9 - 10} and this phenomenon was also observed in the REACH Registry cohort. However, data from the REACH Registry also demonstrate that patients with established atherosclerosis in more than 1 vascular bed had substantially higher event rates than patients with atherosclerotic disease in only 1 vascular bed. Among participants with atherosclerotic disease in 3 or more vascular beds, the rate of cardiovascular events or hospitalization for revascularization or a cardiovascular event was 26.29%. These rates were more than 5 times higher than rates for patients with multiple risk factors and more than double the rate for participants with atherosclerotic disease in only 1 vascular bed. These findings underscore the particularly high risk of major clinical events experienced by patients with clinically manifest atherosclerotic disease in multiple vascular beds. These data provide important prognostic information for physicians and patients.

In the latter half of the 20th century, information about the epidemiology of cardiovascular disease from the Framingham Study and other longitudinal cohort studies has led to major advancements in the ability to prevent and treat cardiovascular disease. These observational studies typically included approximately 5000 participants identified from community-dwelling settings.^{2 ,11 - 12} In the 21st century, Internet capabilities, electronic data entry, and other technological advancements provide opportunities for a new type of study with exceptionally large sample sizes, international scope, and the potential to provide timely information about current trends in disease incidence, treatment, and outcomes. For example, the recently announced Kaiser Permanente Research Program on Genes, Environment and Health¹³ aims to recruit 500 000 patients from members of its northern California health maintenance organization and follow them up for decades to gain information about the interaction between genes, the environment, and disease. Similarly, the REACH Registry may represent a novel approach for epidemiological research with the ability to collect data rapidly on tens of thousands of study participants. The REACH Registry is unique because of its particularly large sample size, its international scope, and the identification of participants from physician office practices. The latter characteristic increases the generalizability of study findings to patients routinely encountered by practicing physicians.

An important limitation of the REACH Registry includes the possibility of bias in physician selection of participants for study. The study was designed to enroll consecutively eligible patients from physician practices.¹⁴ However, no enrollment logs were maintained to monitor the extent to which consecutive enrollment of eligible patients occurred.¹⁴ It is conceivable that the sickest patients were those most easily identifiable as meeting study eligibility criteria. The REACH investigators sought to reduce the possibility of selection bias by aiming to enroll patients within each office practice over a relatively short period (5 days) to encourage consecutive identification of study participants. REACH investigators reported that 5587 physician practices participated in the study, for an average of 12.7 patients from each practice contributing to the registry. Assuming that participants in each office practice were enrolled over an average of 5 days, as originally intended, each practice would have identified approximately 2 to 3 patients per day for enrollment. Thus, there appears to be opportunity for selection bias because a typical busy clinician may treat 20 to 30 patients per day. Because enrollment logs were not maintained, it is not possible to compare characteristics of eligible participants with eligible nonparticipants.

Another study limitation is that office practices were not randomly selected for participation.¹⁴ The degree to which physicians participating in the REACH Registry are comparable with other nonparticipating physicians is unknown. Also, outcomes, such as cause of death or hospitalization, were collected from more than 5000 participating physician practices. Event adjudication was not performed, and uniform definitions for outcome events were not provided. There is potential for error or variation in the methods used across the various physician practices to adjudicate outcome events.

Although the REACH Registry did not present data on quality of life or disability, the high rates of cardiovascular events and hospitalizations for cardiovascular disease are expected to be frequently accompanied by decrements in quality of life and mobility. In support of these associations, the REACH Registry reports that among 14 406 patients who were working full time or part time at baseline, 50.34% of those who experienced an event were no longer working at the 1-year follow-up compared with 29.79% of those who did not experience an event.

The ability to reduce the high rate of cardiovascular events and hospitalizations observed in the REACH Registry depends in part on provision of optimal medical therapies in patients at high risk for cardiovascular events. Yet, previously published data from the REACH Registry document globally suboptimal treatments for patients with established atherosclerotic disease and patients with multiple risk factors for atherosclerotic disease. Investigators from the REACH Registry previously reported undertreatment of study participants with statins and antiplatelet therapies, even though these therapies have proven benefit for patients with or at risk of established atherosclerotic disease.¹⁵ The high prevalence of overweight and obesity previously reported in the REACH Registry adds to the challenge of reducing progression of cardiovascular disease.¹⁵ Thirty-seven percent of Reach Registry participants were overweight, 36.5% were obese, and 5.8% were morbidly obese. Prevalences of hyperglycemia and impaired fasting glucose were 4.9% and 36.5%, respectively, among REACH Registry patients without a history of diabetes mellitus.¹⁵ These sobering findings combined with the high event rates in the REACH Registry underscore the challenges facing the international community with regard to cardiovascular health.

The REACH Registry demonstrates that the cardiovascular disease epidemic remains a critical and urgent international public health problem. Despite recent substantial scientific progress in the understanding of cardiovascular disease pathophysiology and optimal therapies for cardiovascular disease, major challenges remain to prevent cardiovascular events and disability in patients with established cardiovascular disease. Public health infrastructures and health care systems must be developed to facilitate global implementation of optimal therapies for cardiovascular disease and reverse the increasing prevalence of obesity, physical inactivity, and their associated complications.