BACKGROUND: Atherosclerosis is the most common condition that leads to cardiovascular disease and death. Risk factors include age, high cholesterol, smoking, diabetes, being overweight and especially, hypertension. Atherosclerosis can affect the arteries supplying blood to the heart, brain and legs. Blockages in the arteries form, with plaque build-up.

TREATMENT: Angioplasty/stenting or bypass surgery are standard ways of opening these blocked arteries and restoring blood flow, but sometimes blockages can be so extensive that these methods don't work. Also, the blood vessels may be too small.

PERIPHERAL VASCULAR DISEASE: Peripheral vascular disease (PVD) refers to arteries becoming blocked that supply blood to the legs. It affects 5 percent of the population older than age 50. Emory Cardiologist Arshed Quyyumi, M.D., says, "A vast majority of people are unaware of the fact that they have peripheral vascular disease until the blockages are so severe that they start to develop symptoms." Symptoms start off as pain in the legs while walking. A high blockage may lead to pain in the thigh or buttock; a lower blockage may cause pain in the calf muscle. People experience an achy sensation or cramping while moving, called intermittent claudication. As the disease progresses, they start to have pain while at rest as well. Dr. Quyyumi says, "By this time, the blood flow to the legs is so diminished that it is barely able to keep enough flow so that there is no ischemia lack of oxygen to the muscles." Eventually, gangrene may set in, and patients may even need an amputation.

UNDER STUDY: Dr. Quyyumi and his colleagues at Emory are studying a growth factor that helps the body grow new blood vessels. They randomly assigned 45 patients with intermittent claudication to either placebo or one of three doses of granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates the bone marrow to produce endothelial progenitor cells, which in turn help form new blood vessels. Patients had the three-times daily treatment for two weeks and underwent treadmill tests to see how long they could exercise pain-free. Researchers found patients were in fact able to exercise for slightly longer. Also, blood vessel function, which was about one-third of a normal level in patients prior to the study, improved to about 50 or 60 percent after the study's completion. That put patients about halfway to normal. Dr. Quyyumi says, "That is a pretty substantial improvement in a group of individuals who have very advanced disease, so it was very encouraging to see that they were able to get that kind of improvement." He adds, "The implications are very exciting because one way we think that cardiovascular disease can be impeded and stopped and even reversed is by improving your blood vessel function. So, if you can improve the health of your lining of your blood vessels, then that whole process can be halted and even perhaps reversed."

FUTURE: Dr. Quyyumi says further research is needed. He explains, "We need to have many more long-term studies and larger studies to actually evaluate this point." However, he does say there are implications for blocked arteries supplying blood to other areas of the body, such as the brain and heart. Stimulating progenitor cells to the heart could improve heart function and prevent heart failure, and for the brain, stroke incidence could theoretically be reduced.