Tell-Tale Genes Pave Way for Blood Test for Coronary Artery Disease (4/2/2008)

Scientists may be one step closer to a simple blood test that could diagnose coronary artery disease (CAD), according to data reported today by researchers from Duke University Medical Center.

The scientists, reporting at the annual meeting of the American College of Cardiology, say they have identified a small handful of genes in circulating blood that can not only identify the presence of coronary artery disease, but also reveal how advanced the disease may be. It is estimated that some 15 million people in the U.S. have coronary artery disease.

Currently, diagnosing CAD can be a long and complex process, often involving multiple electrocardiograms, echocardiograms and stress tests. Even if all of the tests suggest the presence of CAD, the full extent of the problem isn't fully known until a patient undergoes angiography. Angiography is an invasive procedure that involves inserting a catheter into the coronary arteries to determine the extent of blockage, or stenosis.

"A blood test would potentially be a lot cheaper and easier," says Dr. William Kraus, a cardiologist at Duke and the senior author of the study. "In addition, our study shows that the activity of these genes is proportional to the extent of the disease. That means that a blood test based on these genes could not only tell us if someone has CAD, but also how bad the problem really is."

Kraus says patients who receive a positive blood test might be able to short-circuit additional preliminary evaluations and head directly to coronary catheterization, where any blockages could be treated.

The investigators, working with colleagues at the Helios Heart Center in Germany and at CardioDx, a biotechnology company in Palo Alto, California, that is funding the research, used whole genome microarray analysis to compare the genes of 41 patients who had undergone coronary catheterization. Twenty-seven of the patients had blockages or narrowing of their arteries, and 14 did not.

Scientists identified 526 genes that behaved very differently between the two groups. Through additional tests and analysis, they were able to narrow that number to just 11 genes, that when analyzed in a second, independent catheterization group at Duke, were able to differentiate between which patients had clinically significant coronary artery disease and which did not.

"We believe this set of genes is exquisitely sensitive to a number of inflammatory changes that occur when plaque is building up in arterial walls," says Kraus. Kraus says the genes carry tell-tale signs of those changes as they circulate throughout the body, making them useful sentinels of disease.

Investigators say additional work already under way may yield even more genes that could form the basis of a blood test for clinically important CAD.

CardioDX, in collaboration with eight clinical centers including Duke, is also conducting a prospective clinical study designed to validate the set of 11 genes in a larger population.

Note: This story has been adapted from a news release issued by Duke University

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