Study clears protein as cause of heart disease

By Julie Steenhuysen

CHICAGO, Oct 29 (Reuters) - A blood protein linked with inflammation called C-reactive protein does not cause heart attacks and strokes but it may be sign of trouble, Danish researchers said on Wednesday in a finding that may have implications for drug makers.

Many studies have linked higher levels of C-reactive protein, or CRP, with an elevated risk of heart attacks and stroke, and some companies have started developing drugs to lower levels of this protein based on the assumption that it might reduce heart risks. That may have been premature.

"It is not C-reactive protein in and of itself that causes these diseases," said Dr. Borge Nordestgaard of Copenhagen University Hospital in Denmark, whose research appears in the New England Journal of Medicine.

Nordestgaard and colleagues used a unique approach to arrive at this conclusion.

Since people with different genetic make-up are naturally predisposed to have different levels of CRP, the researchers did genetic testing on 50,000 people in Denmark to see if people with naturally high CRP levels had higher heart risks.

"We simply looked at those with lifelong high levels due to C-reactive protein genetic variation versus those with medium and low levels," Nordestgaard said in a telephone interview.

"It turned out that even if you have genetically high levels, you have exactly the same risk of heart disease or stroke as if you have genetically low levels," he said.

And because the study was so big, it has enough statistical power to answer the question about CRP.

"Because we have 50,000 people, we can show for sure if C-reactive protein was causative, we can predict how much it increased risk, and we can rule it out completely," he said.

And rule it out they did. "This is really, really strong," Nordestgaard said of the finding.

Instead of a cause, Nordestgaard said he suspects CRP is simply a sign of atherosclerosis, in which fatty material called plaque slowly builds up and narrows artery walls.

"Atherosclerosis is an inflammatory disease. So, C-reactive protein is simply measuring how inflamed is the atherosclerosis you have," he said.

"If you have atherosclerosis with a lot of inflammation, there is a bigger chance that these plaques will erupt and lead to myocardial infarctions (heart attacks) and strokes."

Nordestgaard said the findings are likely bad news for companies developing compounds that lower levels of CRP.

"I think they should seriously consider whether it's a good idea to spend money developing these drugs," he said, noting CRP is one of the body's natural defenses against disease.