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June 13, 2006 -- 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 U.Va. 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 U.Va. 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.
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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