College of American Pathologists
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The link with peripheral arterial and cerebrovascular disease

November 2001
William Check, PhD

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Since atherosclerosis is a generalized process in the vasculature, risk factors for cardiac disease are also potential markers for peripheral arterial disease (PAD) and cerebrovascular disease (CVD). In fact, says cardiologist Dr. Alan T. Hirsch, associate professor of medicine at the University of Minnesota Medical School, who specializes in PAD, "Many general biochemical markers for atherosclerosis were first devised and tested in PAD and later tested in the heart."

By the time a patient presents with peripheral disease, large segments of leg or aortic vessels are involved—up to 10 or 15 cm, compared with only a few centimeters in the coronary or carotid arteries. "So a high atherosclerotic burden is already present when PAD is recognized clinically," Dr. Hirsch says. "This would increase the strength of association between the marker of atherosclerosis and short-term risk of ischemic vascular events."

Homocysteine was originally described 15 years ago as a risk factor for peripheral arterial disease, while Lp(a), C-reactive protein, and the metabolic syndrome also have all been associated with PAD. However, when it comes to routine clinical practice, Dr. Hirsch says: "As in coronary disease, most vascular specialists remain uncertain as to the relative importance of these novel risk factors for patients with PAD in routine clinical practice. In patients with average clinical presentations of PAD, we tend still not to measure new risk factors but restrict our evaluation to classical risk factors. We tend to perform novel risk factor evaluations for ’atypical presentations of PAD’ that are not adequately explained by the individual’s standard cholesterol measurements or other risk factors, such as patients <55 years of age or with rapidly progressing disease."

Cerebrovascular disease is part of a generalized process as well, says Barbara Crain, MD, PhD, associate professor of pathology at the Johns Hopkins University School of Medicine. "Most infarcts in older adults occur in the setting of atherosclerotic cardiovascular disease," she says. Cerebral infarcts can originate directly from atherosclerosis affecting intracranial vessels or the carotid artery or secondary to cardiac arrhythmias or mural thrombi in the heart associated with chronic arrhythmias. As a result, Dr. Crain says, "Risk factors for coronary disease are pretty much the same for stroke."

Interest in C-reactive protein in connection with stroke derives from the fact that "atherothrombosis requires not just lipids, but also inflammation," Dr. Crain says. "Certainly there is evidence that aspirin is useful for stroke prevention," she adds, "but it is not clear whether that is due to anti-clotting or anti-inflammatory effects."