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Key Blood Test Protein May Not Cause Heart Disease

WEDNESDAY Oct. 29, 2008 -- High blood levels of C-reactive protein do not increase the risk of heart disease and stroke, a new study suggests.

The inflammation-linked molecule has gained prominence in recent years as a possible marker of heart disease. But the question remained -- does the protein only reflect cardiovascular woes, or does it help cause them?

The new study, based on detailed genetics, suggests that C-reactive protein (CRP) does not help spur heart disease.

"The most likely explanation is that atherosclerosis that is not clinically manifested leads to increased CRP levels," said study author Dr. Borge G. Nordestgaard, a professor of genetic epidemiology at the University of Copenhagen. Atherosclerosis involves a thickening of arteries that can result in a blockage of blood vessels that can cause heart attacks and strokes.

Nordestgaard and his team published its findings in the Oct. 30 issue of the New England Journal of Medicine.

A number of studies have found an association between high blood levels of CRP and increased risk of heart disease and stroke -- the same sort of association that led to suspicions that high blood levels of LDL cholesterol might help cause those problems.

Years ago, the cholesterol theory was proved by controlled trials that showed that lowering cholesterol levels by dietary changes or drug treatment decreased the risk of heart disease and stroke. However, such studies are not possible with CRP because there are no drugs that affect blood levels of the protein.

So, Nordestgaard and his colleagues turned to the ultimate source for the variety between individuals' blood levels of CRP -- genetics. Some people are genetically programmed to have high levels of CRP, while others have genes giving them low levels of the protein.

The Danish researchers performed genetic studies on more than 10,000 people, looking at four variant forms of the CRP genes.

In theory, people whose genetic profile gave them high levels of CRP should have an increased incidence of ischemic diseases such as heart attack and stroke -- if the causal theory was true.

But no such relationship was found, Nordestgaard said.

"So, we cannot say that high CRP levels per se lead to ischemic vascular disease," he said.

By contrast, a study of the genes for apolipoprotein E -- a protein that governs blood levels of cholesterol -- did find such an association for people in the study. People genetically destined to have high levels of cholesterol did have a higher risk of heart disease and stroke, the study found.

But one expert said the findings should be treated with caution. Dr. Peter W. F. Wilson is a professor of medicine at Emory University and a researcher on the role of CRP as a risk factor.

The Copenhagen effort is "a definitive genetic study," Wilson said, but he added that genetics still has a limited role in assessing a person's overall risk.

"Whether you can truly say how important a genetic marker is in middle-aged adults in the modern era, when you have many other factors to consider, is not certain," he said. "My guess is that a lot of these people were being treated with statins, and that might have something to do with the results."

Statins -- drugs such as Lipitor, Pravachol or Zocor -- are taken to reduce cholesterol, but they also might affect CRP levels, Wilson noted. And there are "a fair number of lifestyle and metabolic things that increase CRP -- obesity, being female, smoking, inflammatory conditions such as arthritis," he said. "On the other side, there are medications that can lower CRP levels."

CRP does have a role as a risk factor, Wilson believes. "The question is, how broad is its effect and how should clinicians and researchers use CRP information?" he said. The results of several soon-to-be-released studies, including one that he has done, will help answer the question, Wilson said.

More information

The conventional wisdom on the role of CRP in heart disease and stroke is described by the American Heart Association.

Posted: October 2008


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