Old technology helps find new test for leg artery disease

CHARLOTTESVILLE, Virginia - Between 8 and 12 million Americans are affected by peripheral arterial disease, or PAD, where the arteries that bring blood to the legs are blocked by atherosclerotic plaque. The incidence of PAD is expected to rise in coming decades as the population ages, one reason it's vital to develop new methods to diagnose the severity of PAD and develop new drugs to treat it.

By examining the physiology of patients who exercised under a magnetic resonance imaging scanner (MRI), doctors at the University of Virginia Health System have devised a new test to diagnose and follow peripheral arterial disease. This test shows promise in helping drug companies test new PAD medications and, perhaps in the near future, may give doctors the ability to tell which patients are at risk for developing PAD-related complications and require stenting, bypass surgery or even amputation of a leg.

A UVa cardiologist, Dr. Christopher Kramer, and his colleagues, measured how fast the leg muscles of patients with PAD, and people without PAD, recovered a phosphorus substance called phosphocreatine (PCr), the major energy "store" in muscle cells. Tests at UVa on 20 patients with mild to moderate PAD and 14 people without PAD, showed that the median time to recover phosphocreatine at the end of exercise in PAD patients was three times slower, 91 seconds in the PAD group versus 35 seconds in the normal group.

"Not only is this a good test that can discriminate patients with PAD from those without the disease," Kramer said, "but a longer exercise time was a marker of worse outcomes in PAD patients. Those patients with events, including amputations and surgery, had a longer recovery time." Kramer's findings are published in the June 6 issue of the Journal of the American College of Cardiology found on the web at: http://www.cardiosource.com/jacc/index.asp

What was unusual is that the UVa doctors stepped back in time and used a measurement technique developed in the 1970's called MR spectroscopy, the forerunner to modern MR imaging. "We were somewhat surprised that of all new tests for PAD that we have been developing, the one that seemed to work the best is spectroscopy. It's relatively simple and not particularly sexy, but very accurate physiologically," Kramer said.

All of the patients tested exercised to exhaustion on a special push-pedal machine in an MRI scanner. A spectroscopy coil in the MRI then took readings of the phosphocreatine level in the legs every 15 seconds for several minutes afterward. "If the blood flow is poor," Kramer explained, "PCr recovery is slow, because the muscle is not getting the energy sources it needs to restore PCr. It is an energy-dependant process."

Right now, doctors use several tests to measure PAD severity, including measuring blood pressure in the ankles and comparing it to blood pressure in the arms. Doctors can also do an angiogram of the artery, using dye to show where blockages exist. But, Kramer said, "if you are following a patient over weeks and months, you don't want to do multiple angiograms if you don't have to, and certainly not x-rays or CT scans because of the radiation and contrast dye involved." Yet another reason this new test may be so valuable.

Kramer said people with peripheral arterial disease often have coronary and cerebrovascular disease as well. The risk factors for PAD include smoking, high blood pressure, high lipids and diabetes. People with PAD generally have pain in the calves when they exercise. Those with severe disease can have pain at rest and tissue loss, including ulcers.

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The study: David C. Isbell, Stuart S. Berr, Alicia Y. Toledano, Frederick H. Epstein, Craig H. Meyer, Walter J. Rogers, Nancy L. Harthun, Klaus D. Hagspiel, Arthur Weltman, and Christopher M. Kramer. Delayed Calf Muscle Phosphocreatine Recovery After Exercise
Identifies Peripheral Arterial Disease.
J Am Coll Cardiol 2006 47: 2289-2295


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