The clinical manifestations of atherothrombotic disease include strokes and transient ischemic attacks, critical limb ischemia, angina, and the full spectrum of acute coronary syndromes ( Fig. 3-1 ). The benefits of lifestyle modifications and aggressive risk reduction therapies for prevention of these ischemic events are well established. Prior studies investigating risk factors associated with atherothrombosis have had several limitations, including confinement to a single geographic locale or ethnic group, a particular subtype of atherothrombosis (i.e. coronary artery disease [CAD] only, cardiovascular disease [CVD] only, or peripheral artery disease [PAD] only), and only those patients participating in clinical trials. The objectives of the RE duction of A therothrombosis for C ontinued H ealth (REACH) registry were several, including an investigation of traditional and emerging atherothrombotic risk factors and a comparison of treatment modalities in individuals with various risk factor profiles. Additionally, the registry allowed for a global assessment of the extent of atherothrombosis and its associated clinical outcomes in a geographically and ethnically diverse population deemed high risk for or with stable atherothrombotic disease. Importantly, the results aimed to provide an accurate, contemporary reflection of actual real-world practice.
The international, prospective, observational registry enrolled from December 2003 to June 2004 a total of 67,888 outpatients 45 years or older from 44 countries, consisting of 5473 physician practices. The patient population included individuals with three or more atherothrombotic risk factors and patients with established CAD, CVD, or PAD. The rate of symptomatic polyvascular disease was 15.9% in those with established atherothrombosis ( Fig. 3-2 ).
Risk factors could include diabetes mellitus, hypertension, hypercholesterolemia, smoking, advanced age, asymptomatic carotid artery stenosis 70% or more, diabetic nephropathy, and low ankle-brachial index (ABI < 0.9). Baseline data collected on each participant at enrollment included demographic information, employment status, medical history, risk factors, and medical therapies. Clinical events, data regarding hospitalizations, employment status, and medical treatments were recorded at 1- and 2-year follow-up.
Baseline Demographics and Treatment of Traditional Risk Factors
The prevalence of classic risk factors for CAD, CVD, and PAD was consistent worldwide and included high rates of hypertension, diabetes mellitus, and hyperlipidemia. Hypertension was the most prevalent risk factor, found in 81.8% of the population. The proportion of participants with hyperlipidemia was 72.4%, and 44.3% of patients had diabetes mellitus. Although not as common as these three risk factors, the registry revealed the global extent of obesity (overall rate of 29.9% as defined by body mass index [BMI]; 46.5% as defined by waist circumference) and confirmed its emergence as a major health care problem worldwide. Although similar in most geographic locales, the rate of obesity was highest in North America, occurring at an alarming rate of 36.5%. This finding should serve as advance notice to the entire world, particularly developing nations, regarding the importance of patient and physician education on lifestyle measures to combat this growing epidemic.
The REACH registry also demonstrated the current divide between actual clinical practice and guideline-recommended treatments for patients with or at risk for atherothrombotic disease ( Fig. 3-3 ). This gap was universally present throughout the world, regardless of disease subtype or physician specialty. The rates of undertreated hypertension, undiagnosed hyperglycemia, and impaired fasting glucose (in individuals not known to be diabetic) were 50%, 4.9%, and 36.5%, respectively. Similarly, the rates of elevated cholesterol levels at baseline were equally impressive, varying among geographic regions from as low as 24.4% in Australia to as high as 64.4% in Eastern Europe. The overall use of statins was 69.4%; however, this differed depending on the disease subtype, ranging from 56.4% in those with cerebrovascular disease to 76.2% in those with coronary artery disease. The use of antiplatelet therapy was 78.6% in the total population, whereas only 53.9% of those patients at risk for atherothrombotic disease were on this therapy. Although medication use was suboptimal worldwide, there was some variation of use depending on geographic locale and physician specialty. Prescription of statin therapy ranged from as low as 44.6% in Japan to as high as 82.4% in the Middle East. Among physicians, cardiologists were most likely to prescribe statin and antiplatelet therapy.
The disparities between the guideline-recommended therapies and the real-world care of patients with established atherothrombotic disease were slightly diminished in those individuals with prior history of revascularization. Among the 18,467 patients in the REACH registry with a history of transient ischemic attack (TIA) or ischemic stroke, there was a significantly increased use of antiplatelet agents (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3 to 1.5; P < .0001) and statins (OR, 1.8; 95% CI, 1.6 to 2.0; P < .0001) in those who had a history of carotid endarterectomy. Similarly, in the 40,450 patients with established CAD, the use of secondary medical preventive therapies was influenced by the patient’s coronary revascularization history. In those with a history of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), the use of antiplatelet therapy and lipid-lowering therapy was significantly higher than that observed in those with no prior history of any coronary revascularization procedure. Although prior history of revascularization in these specific patient subsets did translate into better compliance with recommended secondary preventive therapies, their overall use still remained suboptimal.
Because of enrollment delays, baseline data on participants from Japan were analyzed separately from the data from the rest of Asia and published later. Although the Japanese patients in the registry shared many similarities with the global population, there were some significant distinctions seen in this population. The Japanese patients recruited in REACH had higher rates of cerebrovascular disease than the global cohort (39.2% vs. 27.8%). When using definitions outlined by the National Cholesterol Education Program (NCEP), obesity rates in Japan were markedly lower than those seen in North America (10.6% vs. 36.5%). However, Japanese obesity rates increased to 42.1% with the application of the Japanese guidelines for obesity (waist circumference, ≥85 cm for men; ≥90 cm for women).
Both the use and type of secondary preventive therapies prescribed by Japanese physicians were distinctly different than those seen elsewhere. The use of any antiplatelet agent for primary prevention was markedly lower in Japan than that seen worldwide (21.3% vs. 53.9%). Similarly, the use of aspirin in patients with established atherothrombotic disease was also lower in Japan as compared to the rest of the REACH cohort (54.7% vs. 67.4%), whereas the use of other antiplatelet agents was higher in Japan than elsewhere (31.1% vs. 24.7%). In addition to these differences with aspirin therapy, there was also a marked difference in the use of lipid-lowering agents, including statins, in Japan as compared with the global cohort (50.8% vs. 75.2%).
Among U.S. patients with PAD in the REACH registry, there also appeared to be ethnic-specific differences in the rate and treatment of classic cardiovascular risk factors. In the United States, African Americans with PAD were more likely to have hypertension, diabetes mellitus, morbid obesity, and isolated PAD than their white counterparts. Although African Americans with PAD were more likely to have some risk factors for atherosclerosis, they were more likely to have uncontrolled hypertension (blood pressure [BP] ≥ 140/90 mm Hg, 54.9% vs. 38.1%; P < .0001) and hyperlipidemia (cholesterol >200 mg/dL, 41.7% vs. 24.9%; P < .0001) than non-Hispanic whites with PAD. Despite these differences, there were similar cardiovascular outcomes between these two groups at 1-year follow-up. Presumably, these disparities in the undertreatment of blood pressure and cholesterol would translate into adverse clinical outcomes if persistently present over a longer time span.
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