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January 12, 2011

New research offers new insight about peripheral artery disease

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Walking is a painful experience for many of the eight million Americans who suffer lower extremity peripheral arterial disease, or PAD. The condition, which is associated with aging and involves progressive functional decline, can cause heaviness, tightness, cramping or sharp pain in the calf muscle. Symptoms typically disappear with rest and return when walking resumes.

While the prevalence and societal costs of PAD are increasing, the medical community has made limited progress in developing effective therapies for the condition. A major obstacle, says Christopher M. Kramer, M.D., a professor of radiology and medicine at the University of Virginia Health System, is that “we do not completely understand the complex, multi-factorial changes that occur in patients with PAD.”

To gain a better understanding, Kramer and his UVA colleagues used newly-developed magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) methods to assess 85 patients with mild-to-moderate PAD who experienced intermittent leg pain while walking (also known as claudication). Their study is published in the August 11, 2009 issue of the Journal of the American College of Cardiology, which is now posted online . A key finding is that walking abilities in PAD patients could be improved by separate therapies aimed at increasing blood flow and metabolism.

Researchers studied each patient’s most symptomatic leg and measured four factors: large artery plaque deposits (burden), the extent of plaque obstruction in those arteries (stenosis); the amount of blood flowing through calf tissue (perfusion) and the amount of energy being produced on the cellular level (metabolism). To assess patients’ functional capabilities – how far they could walk before the onset of leg pain – the study included a treadmill test and a six-minute walk.

Study results showed that all factors contribute to the leg pain experienced by PAD patients. A finding that Kramer describes as “somewhat surprising” was that two of the factors – energy production in the calf muscle and blood flow in the leg – have no correspondence with each other. “Showing that these two factors are not coupled may be important news for drug developers,” he notes.

According to Kramer, results should not be generalized to all PAD patients because the study only focused on a group with mild-to-moderate symptoms. However, findings indicate that therapies aimed at regressing plaque, increasing tissue perfusion and/or improving cellular metabolism have a potential role in treating PAD.

UVA’s research is continuing. During the next two years, Kramer and his colleagues will assess how cholesterol lowering therapy affects plaque levels, arterial obstruction, blood flow and metabolism in the same 85 PAD patients.

Funding for the UVA study was provided by the National Heart, Lung and Blood Institute, by the National Institute of Biomedical Imaging and BioEngineering and by Siemens Medical Solutions. Study co-authors were: Justin D. Anderson, M.D.; Frederick H. Epstein, PhD; Craig H. Meyer, PhD; Klaus D. Hagspiel, M.D.; Hongkun Wang, PhD ; Stuart S. Berr, PhD; Nancy L. Harthun, M.D.; Arthur Weltman, PhD; Joseph M. DiMaria, BA; and, Amy West, M.D.

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