Early glimmerings of heart disease.

Early glimmerings of heart disease

An experimental method of detecting abnormalities in blood vessel function may someday help physicians identify and treat people with very early coronary artery disease.

Scientists don't know precisely how coronary artery disease begins, but most believe it involves damage to the endothelium, the inner lining of blood vessels, which plays a key role in the vessels' ability to contract and relax. Some suggest the disease starts when sections of the vessles lose their ability to regulate dilation and constriction. These sections tend to constrict, accumulating cholesterol and other fatty deposits that can narrow them further. Called atherosclerosis, the condition can lead to a heart attack.

Joseph A. Vita at the Harvard Medical School in Boston and his colleagues studied 34 people who had no detectable evidence of clogged arteries as measured by angiography, an X-ray examination of the blood vessels that allows doctors to visualize plaque buildup. Despite the normal test results, all of these patients had experienced chest pain or other symptoms that had led their doctors to suspect the beginnings of coronary artery disease.

The Boston researchers gave each patient an injection of acetylcholine, a substance produced by nerve cells that causes healthy coronary arteries to dilate. Of the 34 patients, 18 responded to this test with a narrowing, rather than opening, of blood vessels. Looking back at the subjects' medical histories, the researchers found that patients whose arteries constricted in response to the injection tended to have more heart disease risk factors, such as high blood cholesterol or a family history of the disease, than did those who responded normally.

Vita says the abnormal test response may represent the glimmerings of atherosclerosis that go undetected in routine tests such as angiography. Alterntively, problems with vessel dilation may precede plaque buildup, he says. The Boston team plans to follow the 34 to see which individuals go on to develop full-blown coronary artery disease.

Vita and his colleagues are also investigating the acetylcholine test as a way to help identify heart transplant patients who will get advanced atherosclerosis. Some heart transplant patients develop a rapid accumulation of debris on their vessel walls, and thus face a high risk of heart attack. Preliminary results from this study suggest that acetylcholine can help predict which transplant patients will go on to develop atherosclerosis.

Although the test is too costly and invasive for use in screeining the general population. Vita's research may lead to a practical method of identifying the first signs of heart disease in especially high-risk patients, comments Suzanne Oparil of the University of Alabama at Birmingham. The findings could even lead to treatment aimed at preventing coronary artery disease, she adds.

Treatment-oriented research is already underway. Vita's group is currently using the acetylcholine test to see whether a fish oil regimen would improve the constricted vessels' ability to dilate. In a preliminary study, the scientists put eight patients with narrowed coronary arteries on a six-month regimen of fish oil. Prior to treatment, all eight had vessels that constricted after acetylcholine injection. After treatment, six showed vessel dilation in response to the injection. These results suggest fish oil can improve the vessels' ability to relax, Vita says.

Scientists can't say exactly how fish oil would improve arterial tone, but Vita suggests it may stimulate endothelial cells to release endothelium-derived relaxant factor, a substance that normally causes blood vessels to dilate. Animal research suggests diseased coronary arteries don't produce enough of this substance, he says.