Tests for Heart Risk Being Developed

      - Doctors are closing in on new blood tests that could help pinpoint which patients are at elevated risk of suffering a heart attack or dying from heart disease.

      In pursuit of the perfect predictor test, doctors have identified several markers in the blood, including C-reactive protein and a new enzyme called phospholipase A2, both indicators of inflammation, which has been associated with heart attacks.

      Two new studies in the current issue of the New England Journal of Medicine offer more evidence for the use of such markers in predicting future heart problems, even in patients with no obvious risk factors.

      Used in conjunction with cholesterol checks, stress tests, and computerized tomography, or CT scans, these blood tests may allow doctors to better understand which patients would most benefit from anti-inflammatory drugs or other treatments.

      Ready for Use?

      While most doctors say one of these markers are ready for prime-time use, others argue most are still primarily a research tool that should only be used to better understand the process of heart disease and to develop treatments.

      "Probably, it is a little early for this information to have significant clinical implication," says Momtaz Wassef, head of the atherosclerosis research group of the National Heart Lung and Blood Institute''s division of heart and vascular disease.

      Dr. Daniel Rader, assistant professor of medicine at the University of Pennsylvania School of Medicine, says in an editorial in the current New England Journal of Medicine that traditional risk factors - such as smoking, high blood pressure and high cholesterol levels - can only predict about 50 percent to 60 percent of an individual''s risk.

      "The addition of other factors that would increase the predictive ability would improve the accuracy of decisions," he writes.

      Inflammation''s Role

      Doctors do not believe these inflammatory markers are what necessarily causes a heart attack, but that they can indicate a tendency for it, even years before an attack occurs.

      C-reactive protein, for example, is normally absent from the blood but is produced by the liver in response to an infection and indicates inflammation.

      Inflammation may predict an oncoming heart attack because doctors believe that plaques that develop on blood vessel walls. If plaques become inflamed and rupture, they can clog the blood vessel and cause an attack.

      Test Available

      Currently, the C-reactive protein is the only marker for heart disease commercially available from doctors'' offices and medical centers. Quest Laboratories, a diagnostic laboratory in Teterboro, N.J., performs the highly sensitive test.

      The test can be tacked on to a standard blood work-up for about $35 to $50, which is usually covered by insurance, says Tom Luhr, spokesman for Dade Behring, a Deerfield, Ill., company that manufactures the test used by Quest. Since the test was approved by the Food and Drug Administration last November, nearly a million people have been tested for the protein, he says.

      The basis for the test was work done by Paul Ridker, a cardiologist at Brigham and Women''s Hospital in Boston, and others who have shown that C-reactive protein can predict risk of heart attacks, even in healthy people.

      The test is useful, Luhr says, because around 30 percent to 40 percent of those who suffer a heart attack will not have had high lipid levels, a well-known risk factor. "Those people are a population that will benefit from [the test]," he says.

      The test, however, is not widely used yet because many doctors simply don''t know it is now available, Ridker says.

      Study Expands Population

      But a study published in the current Journal suggests C-reactive protein may also be able to predict long-term mortality in patients who already have been diagnosed with coronary artery disease. Swedish researchers followed 917 patients with heart disease for an average of three years and found those with the highest levels of C-reactive protein had three times the chance of dying from heart disease.

      Dr. Rodman D. Starke, chief science officer for American Heart Association, says the study is a good indication the test may be useful for doctors in hospital settings treating those who have already suffered a coronary event.

      "If we segment that high risk group with a marker of even higher risk," he says, "maybe it would motivate those people to do everything assiduously right [to prevent another attack]."

      But, he adds, the association doesn''t believe that C-reactive protein testing is ready to be applied to screen the populace as a whole. "Not a lot of providers are comfortable knowing how to assess its value," he says.

      Guidelines Under Development

      However, Dr. Chris Cannon, a cardiologist at Brigham and Women''s, says research he and others are conducting will soon help establish guidelines about which patients should have this test and what should be done with them.

      Waiting for clear guidelines before recommending widespread testing is probably reasonable, Cannon says. In the meantime, "the field of C-reactive protein is exploding," he adds. "I personally use the tests in selected patients to serve as a red flag for more aggressive treatments."

      The other newly identified marker, lipoprotein-associated phosphohlipase A2, an enzyme also associated with inflammation, may also be a potential marker for heart attack risk among healthy people.

      This study was reported by Scottish researchers in a second Journal study that looked at 580 men with elevated cholesterol levels but no history of heart attack. The researchers found those who had high levels of the marker had twice the chance of having a heart attack during the six years of the study compared to those with low levels of the enzyme.

      However, most experts agreed it is too soon to offer this test commercially. "We need to watch and see what happens with that," Starke says.

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