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Biomarkers Predict Heart Deaths
Date:5/14/2008

Studies find they might add to traditional risk factors

WEDNESDAY, May 14 (HealthDay News) -- A bundle of four offbeat biomarkers accurately predicted the risk of death from cardiovascular disease in a study of older Swedish men, researchers report.

It is just a preliminary finding in a long process that might one day lead to widespread medical use of these biomarkers in addition to well-established risk factors such as high blood pressure and cholesterol, said Dr. Johan Arnlov, a researcher at Uppsala University, and lead author of a report in the May 15 issue of the New England Journal of Medicine.

But the study is important, because it goes against the widely publicized findings of two American trials which found that unconventional biomarkers did not add clinical information over and above that provided by established risk factors.

"There are two major explanations why there is a difference in our study," Arnlov said. "First, our study was based on a cohort entirely of elderly men. In the elderly, established cardiovascular risk factors have been shown to be less predictive. Also, we used entirely different biomarkers than in those studies. Our biomarkers may be better risk markers."

In the study, Arnlov and his colleagues tested 1,135 men, average age 71, for four body chemicals: troponin I, brain natriuretic peptide (BNP), cystatin C and C-reactive protein. Over a 10-year follow-up, "all of the biomarkers significantly predicted the risk of death from cardiovascular causes," the researchers said. The predictive value was as great for men who did not have cardiovascular disease at the start of the study as for those who did.

Tests for the four markers already are in clinical use, in some cases widely. Tropinin I is produced when heart muscle is damaged, and a test for its levels is used to assess the probability of heart damage in people who have chest pain. Cystatic C levels test for kidney function, BNP tests measure the effectiveness of treatment for heart failure, and C-reactive protein level is a measure of overall inflammation.

"If our findings are validated, they quickly will be used for predictive purposes, because they are widely available," Arnlov said.

But he was quick to point out that the study results "were based entirely on elderly Swedish men. They must be validated in other age groups, in women and in other ethnic groups as well."

Getting that validation is likely to take many years, Arnlov said. Beyond that, he said, "it is also important to realize that although we see this association, it should not be construed as evidence of benefit in reducing these levels." The benefits of reducing established risk factors such as high blood pressure and cholesterol are well-known, he said.

"This concept of using disease markers to stratify disease has a lot of promise," said Dr. James A. de Lemos, an associate professor of medicine at the University of Texas Southwestern Medical Center, and co-author of an accompanying editorial. "This is a move forward, but much has to be done before any of this will be ready for routine clinical use."

Still, the Swedish researchers did show predictive power is using the latest medical technology to test for the biomarkers, de Lemos said. "All of the tests they measured are used for other indications," he said. "The application is novel."

Whether the tests could be used to guide preventive measures is another issue, he said. "We have to know that there is something we need to do to mitigate the risk," he said.

Another report in the same issue of the journal added evidence for testing blood troponin levels in treatment of heart failure, the progressive loss of ability to pump blood.

A study of almost 85,000 people hospitalized for severe heart failure found that 8 percent of those with high troponin levels died in the hospital, compared to 2.7 percent of those with normal levels, said a report by a group led by physicians at the Cleveland Clinic.

"A positive troponin test is associated with higher in-hospital mortality, independently of other predictive variables," they reported.

More information

Learn about the established risk factors for cardiovascular disease from the American Heart Association.



SOURCES: Johan Arnlov, M.D., Ph.D., researcher, Uppsala University, Sweden; James A. de Lemos, M.D., associate professor, medicine, University of Texas Southwestern Medical Center at Dallas; May 15, 2008, New England Journal of Medicine


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