New test may diagnose heart disease risk better

November 24, 2003

A new, unprecedented test created at UCLA may offer a better way to diagnose heart disease risk for patients who develop coronary heart disease despite normal cholesterol levels.

Research published online in Circulation on Nov. 24 reports that testing the inflammatory and/or anti-inflammatory properties of a patient's HDL cholesterol may be a more accurate way of predicting heart disease risk than simply measuring the level of HDL cholesterol in the body, which is commonly used in practice.

The new UCLA test gauged whether patients' HDL provided the normal anti-inflammatory protection against coronary heart disease- or had become pro-inflammatory, which actually enhances the disease process. HDL is typically known as the "good cholesterol," and normally functions to protect against vessell wall inflammation, which can lead to heart disease.

"Unfortunately there are many patients that develop coronary heart disease despite having normal cholesterol levels and no other risk factors," said Dr. Ben Ansell, first author and director of the UCLA Center for Primary Care-Based Cardiovascular Disease Prevention. "Traditionally, normal to high HDL levels are associated with low heart disease risk, but some of these patients have pro-inflammatory HDL, and thus may not be protected, and even be at higher risk. Approximately 30 percent to 40 percent of all heart attacks occur in persons with normal or high HDL-cholesterol levels."

In addition, the study found that for patients testing positive for pro-inflammatory HDL, statin treatment significantly improved their HDL function.

Currently no clinically available test exists that measures the inflammatory properties of HDL. Although the study used two new blood testing methods developed at UCLA, one of the methods -- called the cell-free HDL function test -- appeared to have greatest potential for clinical application given its ease of use.

"The new testing method may offer not only an additional tool to help diagnose specific patients that may be at risk of coronary heart disease, but also help us in better understanding the functionality and role of HDL and in testing new drugs to treat pro-inflammatory HDL," said Dr. Alan Fogelman, senior author, professor and executive chair, department of medicine, David Geffen School of Medicine at UCLA.

The study examined several groups of people. The first det of patients had symptomatic coronary disease despite HDL cholesterol levels that were more than twice the American average. Researchers used the two testing methods to measure if these patients' HDL either enhanced or reduced inflammatory cell activity- similar to what occurs in the development of coronary disease in the artery wall. In the overwhelming majority, the HDL increased inflammatory cell activity, demonstrating that nearly all of the patients had paradoxically pro-inflammatory HDL cholesterol.

Next, researchers wanted to see whether the tests could distinguish further which patients might have pro-inflammatory HDL in a broader patient sample of patients at high risk for heart disease and also measure the impact of a statin drug on HDL function. This study looked at patients with coronary heart disease or diabetes who were not receiving cholesterol medication. The patients were compared with controls of the same age and sex.

Using the two testing methods, researchers initially assessed blood samples to see whether patients' HDL was anti or pro-inflammatory. The testing was repeated in the high-risk patients after six weeks of daily 40-milligram treatments with a statin called simvastatin (Merck's Zocor).

Researchers found that the inflammatory properties of HDL better differentiated patients from healthy subjects, compared to just checking HDL cholesterol levels alone.

"We found that the inflammatory properties of HDL may be a better, more refined gauge of coronary artery disease risk than looking at HDL cholesterol levels alone -- especially for patients who have evidence of disease or are at high risk for disease such as those with diabetes, but who appear to have normal cholesterol," said Mohamad Navab, professor of medicine, division of cardiology, David Geffen School of Medicine at UCLA.

Researchers also found that statin treatment significantly reduced inflammation caused by dysfunctional HDL, but still not to the level of the normal control group. Ansell noted that although the statin didn't completely normalize HDL for patients with pro-inflammatory HDL, the findings help to explain why aggressive statin treatment may benefit these patients.

The next step, according to researchers, is to conduct larger studies that will validate their findings since the patient groups in these studies were relatively small.

Other authors from the UCLA department of medicine include Susan Hama, Naeimeh Kamranpour, Dr. Gregg Fonarow, Greg Hough, Dr. Shirin Rahmani, Rachel Mottahedeh, Dr. Ravi Dave and Srinivasa T. Reddy.
-end-
The study is funded in part by the U.S. Public Health Service and in part by private funds. Four of the investigators -- Fogelman, Navab, Hama and Reddy -- are also principals of Bruin Pharma, the biotech firm developing the new diagnostic test.

RC581

Rachel Champeau, rchampeau@support.ucla.edu, 310-794-0777.

University of California - Los Angeles

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