October 21st 2004

Exercise Role in Relieving Peripheral Arterial Disease

DURHAM, N.C. – While physicians often recommend exercise to help relieve the symptoms of peripheral arterial obstructive disease (PAOD) -- a potentially debilitating disorder that afflicts one in eight Americans -- they have done so without fully understanding why it seems to help. However, a new clinical trial led by Duke University Medical Centers aims to supply the scientific basis for this clinical practice.

PAOD is characterized by atherosclerotic plaques in the arteries of the leg that can slowly starve muscle of needed nutrients and oxygen. In mild cases, known as intermittent claudication, patients feel muscle pain upon exertion that is only relieved by rest. More severe cases, known as critical limb ischemia, can lead to gangrene or tissue death, often necessitating amputation of the effected limb.

Clinicians have long appreciated that exercise in general can stimulate formation of new blood vessels in skeletal muscle, a process known as angiogenesis. The Duke researchers, collaborating with colleagues at the University of Colorado Health Sciences Center, Denver, believe that this angiogenic response to exercise underlies the improvements in walking endurance and symptom relief of PAOD patients.

The Duke team is now enrolling patients in a clinical trial to test this hypothesis. The trial is supported by the five-year, $3.9 million grant from the National Heart Lung Blood Institute.

"Almost every physician will recommend exercise for their patients with peripheral arterial obstructive disease, but the reality is that we don't really know why it works," said Duke cardiologist Brian Annex, M.D., principal investigator for the trial.

"If we can understand why exercise works, it would be much easier to make our treatments more effective," Annex continued. "The main reason for intermittent claudication is a blockage in the arteries, which then leads to inadequate skeletal muscle perfusion during physical activity. However, the mechanisms by which exercise can improve walking times for patients with intermittent claudication are not completely understood."

It is estimated that between 8 and 12 million Americans suffer from PAOD, an incidence that is slightly less than coronary artery disease. While many patients with PAOD also have coronary artery disease, Annex said that almost half of them have no heart disease. As is the case for coronary artery disease, people who smoke, have diabetes, high blood pressure or elevated cholesterol levels are higher risk of PAOD. Drugs and invasive procedures are used to treat the disorder, but none are particularly effective, the researchers said.

While up to three-quarters of patients do not report symptoms, there is a simple test to screen for PAOD. The ankle-brachial index (ABI), which is the ratio of the blood pressure recorded at the ankle and the arm, can often detect the presence of PAOD. The American Diabetes Association recommends that all diabetics receive annual ABI testing after the age of 50 to screen for PAOD.

"Many people feel that leg pain is just a normal part of aging, but that is not necessarily true," Annex said. "The pain of PAOD is felt in the muscles, and not the joints."

For the trial, which is recruiting patients at Duke and the University of Colorado, researchers plan to enroll 160 participants, equally divided among men and women. These patients will be randomized to either an individualized exercise program conducted at home or to a supervised exercise program on campus. An additional 66 age-matched participants will be recruited to serve as controls by not exercising.

"An important goal of this trial is to document the gender differences in the disease and the responses to exercise," Annex said. "In the past, women have been horribly under-represented in PAOD studies, even though the incidence of the disease in women is similar to men. The results of our trial should help to establish whether current exercise prescriptions are adequate for both men and women with PAOD, or whether different therapeutic strategies are needed."

Because of this focus on gender, the National Institutes of Health's Office of Research on Women's Health is a co-sponsor of the trial, which has been named Angiogenesis and Mechanisms of Exercise Training in PAOD (AMNESTI).

During the three-month trial, researchers will make detailed measurements at regular intervals -- using ABI, magnetic resonance imaging and muscle biopsies to determine if exercise is indeed stimulating the growth of new vessels, and furthermore if these changes correlate with improvement of symptoms.

The researchers will follow such markers as the growth of new capillaries in leg muscles, the occurrence of programmed cell death (apoptosis) within leg muscle, and blood levels of vascular progenitor cells, which are produced in the bone marrow and are responsible for blood vessel repair.

Patients who are interested in enrolling in the PAOD trial should contact Leslie Kelly, recruitment coordinator, at (919) 660-6739 or Kelly045@mc.duke.edu.




media contact : 
Richard Merritt , (919) 684-4148
merri006@mc.duke.edu


contact sources :
Brian Annex , (919) 286-0411, ext. 7258
Annex001@mc.duke.edu

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