Mouse Study Casts Doubt On CRP Heart Disease Test

But one expert dismissed the finding as "not important"

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HealthDay Reporter

MONDAY, May 23, 2005 (HealthDay News) -- A new study involving genetically engineered mice casts doubt on the growing belief that blood levels of C-reactive protein -- an inflammation marker -- are a significant indicator of risk of heart attack and stroke.

Mice engineered first to form artery-blocking deposits of plaque and then to produce excess amounts of CRP did not develop serious cardiovascular problems of the sort that in humans would lead to heart attack and stroke, conclude researchers reporting in this week's issue of Proceedings of the National Academy of Sciences.

The finding adds to evidence that the link between elevated CRP levels and cardiovascular risk in humans "is much more tenuous than is asserted by people who have a vested interest in promoting that story," said lead researcher Dr. Mark B. Pepys, head of the department of medicine at the Royal and Free University College Medical School in London.

That claim was quickly dismissed by Dr. Steven E. Nissen, a cardiologist at the Cleveland Clinic Foundation. He led a study that found blood CRP levels were "significantly correlated with the rate of progression" of artery blockage.

The British study is "not terribly important or helpful," Nissen said. "Mouse models of atherosclerosis are interesting but by no means definitive. I don't think you learn much from these studies where you create a disease in mice rapidly."

Several large, controlled human studies have shown the relationship between CRP levels and cardiovascular risk, Nissen added, "and when you look at studies involving 10,000 patients where you find that CRP is a risk factor, a handful of mice is not important."

But Pepys has been insisting for years that the evidence from human studies is far from convincing. "It is statistically significant, but not so powerful that it adds anything to cardiovascular risk assessment," he said. "In the general population, measuring baseline CRP is a relatively modest predictor, and adds nothing to the established risk factors."

While human studies have shown a relationship between CRP levels and cardiovascular risk, "association does not prove causality," Pepys said.

That is a belief held only by "a group of CRP skeptics who are pushing the idea that it is not terribly important," Nissen shot back. He said it's similar to the opposition once mounted against cholesterol as a potent heart disease marker.

"There was a period when cholesterol skeptics were telling people that cholesterol was not an important risk factor for heart disease," Nissen said. "The same thing is going on with CRP."

CRP has already been accepted as a cardiovascular risk factor by the U.S. Centers for Disease Control and Prevention, he pointed out.

A joint statement by the American Heart Association and the CDC defines CRP blood levels as not being important indicators of heart risk in individuals with less than a 10 percent risk of having a dangerous cardiovascular event over the next 10 years, as measured by other factor such as cholesterol and blood pressure.

However, the statement acknowledges that CRP levels are meaningful in people whose 10-year risk is greater than 10 percent.

Changes in therapy should be considered for persons in this higher-risk group, the statement says, but "benefits of such therapy based on this strategy remain unclear."

More information

The current expert view of C-reactive protein and cardiovascular disease is available from the American Heart Association.

SOURCES: Mark B. Pepys, M.D., Ph.D, head, department of medicine, Royal and Free University College Medical School, London; Steven E. Nissen, cardiologist, Cleveland Clinic Foundation, Cleveland; May 23-27, 2005 Proceedings of the National Academy of Sciences

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