New Debate on C-Reactive Protein Test and Statins

Study Suggests CRP Blood Test May Not Predict Heart Benefits of Statin Drugs

Medically Reviewed by Laura J. Martin, MD on January 27, 2011
From the WebMD Archives

Jan. 27, 2011 -- Cholesterol-targeting statin drugs protect against heart attacks and strokes even when patients have normal LDL “bad” cholesterol and little evidence of systemic inflammation, new research suggests.

Inflammation is a well-recognized risk factor for these cardiovascular events, but the study found that its presence or absence measured by a CRP blood test did not predict how well patients will respond to statins.

The study is published online in The Lancet.

Researchers tested the hypothesis that patients with elevated blood levels of the inflammation-marker C-reactive protein (CRP) derive the most benefit from taking statins and that the drugs may not benefit patients with both normal cholesterol and low CRP.

They did this by analyzing data from more than 20,000 participants in one of the largest statin studies ever conducted. The Heart Protection Study included patients at high risk for heart attack and stroke recruited from 69 hospitals in the U.K. between 1994 and 2001. The patients were treated with a statin or placebo for an average of five years.

Those who took the statin drug Zocor (simvastatin) had a 24% reduction in cardiovascular events, including heart attacks, strokes, and death from cardiovascular causes.

The analysis revealed that patients with the lowest CRP levels had similar reductions in risk as patients with the highest levels of the inflammation marker.

In fact, the risk reduction was about the same for any combination of low or high CRP with low or high LDL cholesterol, the researchers reported.

Assessing Heart Risk

The findings do not mean CRP is of no benefit as a marker for cardiovascular risk, study researcher Jonathan Emberson, PhD, tells WebMD.

But he says it is clear that assessing a patient’s overall risk profile is more important than any single test result when deciding if statin therapy is warranted.

“CRP may be useful to help a physician understand a patient’s absolute risk along with other characteristics like age, sex, blood pressure, and blood lipids,” he says. “But this analysis tells us that a normal CRP doesn’t necessarily mean a statin won’t be beneficial.”

The analysis raises new questions about a widely reported trial known as the JUPITER study, which prompted the FDA to broaden the uses of the statin drug Crestor, made by AstraZeneca.

The JUPITER study showed a dramatic reduction in heart attack and stroke risk in Crestor users with normal LDL and elevated CPR.

Based on this finding, the FDA last year ruled that elevated CRP could be considered a reason for the drug’s use in men aged 50 and older and women 60 and older with one additional cardiovascular risk factor, such as high blood pressure or tobacco use.

As a result, as many as 6.5 million people in the U.S. with normal cholesterol became candidates for the drug, a spokeswoman for AstraZeneca confirmed to WebMD.

In an editorial, Jean Pierre Despres, PhD, of the Quebec Heart and Lung Institute, writes that the new analysis of the Heart Protection Study data “brings more fuel to the healthy debate” about the usefulness of CRP as a predictor of heart attack and stroke risk.

Despres agrees that elevated CRP is clearly predictive of cardiovascular risk. But he says the marker of systemic inflammation is usually seen in people with another cardiovascular risk factor -- obesity.

His own research and that of others suggests a particularly strong association between elevated CRP and belly fat.

“You are not likely to see high CRP in a vegetarian monk training for the Boston Marathon,” he tells WebMD. “By far the greatest driver of elevated CRP in North America is a sedentary lifestyle and carrying too much fat around the middle.”

Because of this, he says, lifestyle modification has to be part of the discussion about how to lower cardiovascular risk.

“Statins are clearly effective, but lifestyle modification is optimal,” he says.

Show Sources


Emberson, J. The Lancet, Jan. 28, 2011; online edition.

Jonathan Emberson, PhD, Clinical Trial Service Unit, University of Oxford, U.K.

Jean-Pierre Despres, PhD, director of research, Quebec Heart and Lung Institute, Quebec City, Canada.

Stephanie Jacobson, spokeswoman, AstraZeneca.

News release, The Lancet.

FDA: “Crestor and the JUPITER Trial,” February 2010.

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