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New biomarker for coronary artery disease?

We know high cholesterol is bad. High BNP may be worse. Some day, physicians may be checking our BNP (B-type natriuretic peptide) levels to determine our risk of developing heart disease. BNP is released from cells of the heart wall when it's under stress.

In fact, assessing BNP levels may turn out to be a better way of detecting coronary artery disease (CAD) than the commonly used cardiac stress test, says Robert Foote, M.D., an assistant professor of medicine and of radiology. The stress test—in which an electrocardiogram (EKG) is taken while someone exercises on a treadmill—often fails to detect ischemia, inadequate blood flow caused by constricted or blocked coronary vessels.

In an initial study funded by the Hitchcock Foundation and published in the Journal of the American College of Cardiology, Foote demonstrated a correlation between ischemia during exercise and increased levels of BNP. In patients with known CAD, he used nuclear perfusion imaging to accurately measure blood flow to the heart. A radioisotope, given intravenously during a stress test, distributes itself through heart muscle in proportion to blood flow. Images taken by a special camera then show which vessels are blocked.

"We have strong evidence that ischemia triggers the release of BNP in the blood stream," says Foote. Of 74 patients with CAD, over 90% showed an abnormal increase in BNP after exercise, while only 37.5% of their EKGs showed abnormal patterns.

An increase in BNP levels can be a good thing when a heart is under stress from hypertension, ischemia, stroke, renal failure, heart failure, and the like. BNP dilates blood vessels, increases blood flow to the kidneys, reduces myocardial oxygen needs, and lowers blood pressure. "The net effect is to reduce cardiac workload," explains Foote. "It has so many good properties that . . . it's been synthesized and it's now being used as a drug to treat severe heart failure."

Tool: But Foote is interested in BNP's value as a diagnostic tool. First, however, researchers must determine what's normal. "BNP levels are a continuum," Foote says. "The higher the level, the

A peptide called BNP may be a better biomarker than cholesterol for heart disease, says Foote.

higher the risk." He has found average levels of 25 picograms/milliliter (pg/ml) in healthy athletes (members of the Dartmouth women's hockey team), 55 pg/ml in patients with heart disease but no ischemia, 125 pg/ml in patients with ischemia, and more than 1,000 pg/ml in people with heart failure.

Foote will soon conduct a larger study, funded by Roche Diagnostics, to measure BNP in 400 to 500 patients who come to the DHMC emergency department with chest pain of uncertain cause. He hopes to be able to distinguish people with ischemia from those who have other problems, such as indigestion.

"I would not be surprised if [BNP] became a routine part of risk assessment," says Foote.

Laura Stephenson Carter

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