Caution over much-touted test

A new blood test that may be a better predictor of heart disease and stroke than cholesterol measures catapulted into the headlines recently after a study in the New England Journal of Medicine. The test measures levels of an inflammatory substance, C-reactive protein, that plays a role in cardiovascular disease.

So, should you ask for the CRP test? Probably. It’s cheap -- about $16 -- and already on the market. And it might save your life, especially if a worrisome result gets you to exercise more and eat less. President Bush took the test and passed with flying colors, so perhaps it’s good enough for the rest of us.

An editorial last week in the New England Journal of Medicine took a more cautious view, arguing that “it may be premature” to adopt widespread screening for C-reactive protein.

And there are legitimate caveats. No one is recommending that the test be done routinely for all adults. The experts -- a committee of specialists from the Centers for Disease Control and Prevention and the American Heart Assn. -- are still hashing out who should get it, and a decision is expected soon. If these experts do recommend testing, it may be a limited endorsement, say, for people whose risk is unclear or moderate based on other diagnostic measures. CRP testing would not replace, but rather supplement, cholesterol screening.

A concern of any screening test is that worrisome results could set you on a path of intervention that may do harm as well as good.

For instance, if your CRP test is high, do you just exercise more and eat less? Or do you start taking statin drugs, which can lower CRP as well as cholesterol? The evidence that statins lower CRP is growing, but it’s not conclusive, and statins do carry some risk.

Moreover, once CRP testing is used more widely, in the real world, it may prove not to be such an accurate predictor of heart disease as it was in research labs. After all, cholesterol has not been a foolproof predictor: Half of people who have heart attacks have normal cholesterol.

Finally, much of the work on CRP, including the latest study, has been done by researchers at Brigham and Women’s Hospital, which owns the patents on inflammatory markers for cardiovascular disease. This does not taint the research. But CRP testing is a potentially lucrative business.

That said, the new study, which confirms a considerable body of previous work, seems likely to change the way doctors screen for heart disease.

Led by Dr. Paul Ridker, director of cardiovascular disease prevention at Brigham and Women’s, the new study followed 27,939 healthy middle-aged women for eight years to assess their risk of having a first heart attack, stroke, cardiac bypass surgery or death from cardiovascular causes.

The researchers found, as expected, that women with high levels of both CRP and LDL cholesterol were at high risk of cardiovascular problems, and that women with low levels on both tests were at low risk. The surprise was the women in the middle.

In the study, women with high CRP but low cholesterol actually were at higher risk than those with high cholesterol and low CRP, even though the former group is usually deemed low risk by current screening.

“The CRP story gets more interesting every day,” says Dr. Sidney Smith, chief scientific officer for the American Heart Assn. and professor of medicine at the University of North Carolina at Chapel Hill. “The evidence for its value is compelling, but not as a replacement for cholesterol.”

For years, doctors have known that cholesterol-filled plaques in artery walls pose a significant danger. If these plaques completely block an artery, the heart can be deprived -- sometimes fatally -- of adequate blood flow.

But doctors also know that even if plaques don’t completely block an artery, they can trigger heart attacks if they rupture, releasing blood clots that themselves can block an artery to the heart or brain.

Most heart attacks are actually caused by smaller, “vulnerable” plaques at risk of rupture, says Dr. James Muller, a cardiologist at Massachusetts General Hospital in Boston.

So far, vulnerable plaques, which are filled with inflammatory cells from the immune system, cannot be detected with standard imaging techniques such as coronary angiograms or CT scans.

Enter C-reactive protein, a substance made in the liver and released during infections. Standard CRP tests are used routinely to gauge the degree of inflammatory response in everything from pneumonia to rheumatoid arthritis.

But new, more sensitive cardiac CRP test measures tiny fluctuations at the low end of the range. (A worrisome score on the new test could indicate nothing worse than a common cold; but if a repeat test several weeks later is still high, it may indicate a persistent inflammation in the body, including fragile, inflamed plaques.)

Still, not everyone believes CRP testing is ready for prime time, or that, even if it is, doctors should begin prescribing statins for this reason. Key questions remain, including whether the humble aspirin, an anti-inflammatory as well as anti-clotting drug, might also be used to lower CRP levels.

Still, CRP is the most promising advance in a long time in detecting cardiovascular risk. It makes sense to ask your doctor about it.

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Judy Foreman is a lecturer at Harvard Medical School.