Oct. 29, 2008 -- C-reactive protein is linked to heart disease, but it's an innocent bystander and not a cause of disease, a new study shows.
Inflammation swells cholesterol-crammed artery walls, making the lining of those arteries vulnerable to breaking down or bursting. When the lining of an artery wall is disrupted, a cascade of events is set off culminating in the formation of a blood clot, which can go on to cause a potentially deadly heart attack or stroke. Earlier studies have suggested that CRP plays a key role in this process.
Drug companies already are racing to make drugs that target CRP. But taking aim at CRP will miss the real causes of heart disease, suggests new evidence from Borge Nordestgaard, MD, DMSc, professor and chief physician at Copenhagen University Hospital, Denmark, and colleagues.
CRP and Heart Disease
Fortunately, nature has provided its own version of a clinical trial. Some people carry variant CRP genes that make more or less CRP than the normal CRP gene. Do people with naturally high CRP levels have more heart disease and stroke?
First, Nordestgaard's team measured CRP levels in more than 10,000 people. They found that high levels of CRP increased risk of heart disease by 60% and risk of stroke by 30%. That's the same degree of risk seen in previous studies.
Then the researchers analyzed CRP genes and measured CRP levels in more than 31,000 people. They found that people with certain CRP genes made 64% more CRP than people with the least active CRP genes. This allowed them to calculate that if CRP caused disease, people with the most active CRP genes should get up to 32% more heart disease and up to 25% more strokes.
Finally, the researchers looked at people who actually had heart disease or stroke and compared them to people who remained disease free. The big surprise: People with the most active CRP genes were at no higher risk for heart disease and stroke than were people with the least active CRP genes.
To make sure their calculations were correct, the researchers also studied people with variant cholesterol genes. Those with genes that made the most cholesterol were indeed at highest risk of heart disease and stroke -- almost exactly as their calculations predicted.
This means CRP does not cause heart disease, says cardiologist Heribert Schunkert, MD, director of Germany's Luebeck University Hospital and professor of cardiology at the University of Leicester, England.
"It is pretty definitive. Genetic markers that increase CRP don't increase disease," Schunkert tells WebMD.
Also convinced is Thomas A. Pearson, MD, PhD, MPH, senior associate dean for clinical research at the University of Rochester Medical Center. Pearson led a recent study group that evaluated CRP research for the CDC and the American Heart Association.
"This is a nail in the coffin for the idea that CRP is a causal factor in heart disease," Pearson tells WebMD. "This is a very useful study, and cleverly done, and their conclusion is right on the money."
That conclusion: CRP is an indicator of heart disease and stroke risk, but not a cause.
The Nordestgaard study and an editorial by Schunkert and colleague Nilesh J. Samani, MD, FmedSci, appear in the Oct. 30 issue of TheNew England Journal of Medicine.