A new test called high sensitivity CRP, catapulted into the headlines last week by a study in the New England Journal of Medicine, appears to be better than cholesterol at predicting the risk of heart attack and stroke. The test measures levels of an inflammatory substance, C-reactive protein that plays a role in cardiovascular disease.
So, to cut to the chase, should you ask for the CRP test? Yes. It’s cheap (about $16). It’s already on the market. It could save your life, especially if it a worrisome result gets you to exercise more and eat less. Besides, if it’s good enough for President George W. Bush, who has passed the test with flying colors, it’s good enough for the rest of us.
To be sure, an editorial last week in the New England Journal 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 -yet – 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 Association – are still hashing out who should get it. Chances are their recommendations, due out soon, will initially recommend the test, if at all, only for people whose risk is unclear or moderate based on other tests. In any event, CRP will not replace cholesterol testing, but will be an add-on.
There’s also the concern, present with any screening test, that worrisome results could set you on a path of intervention that could 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 statins, 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, CRP testing might not pan out once it’s used widely, not just in research. After all, cholesterol hasn’t been such a great predictor – half of people who have heart attacks have normal cholesterol.
Finally, just for the record, 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, is paradigm-shaking, poised 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 were actually 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 study provides overwhelming evidence that inflammation is at least as important as LDL cholesterol in predicting vascular risk,” notes Ridker. In fact,25 percent of the US population has elevated CRP levels but normal to low levels of LDL, suggesting that millions of Americans may be at increased risk despite normal or low cholesterol.
“The CRP story gets more interesting every day,” says Dr. Sidney Smith, chief scientific officer for the American Heart Association 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. It will be useful for some patients in combination with other measures of risk.”
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.
Indeed, most heart attacks are actually caused by smaller, “vulnerable” plaques at risk of rupture, says Massachusetts General Hospital cardiologist Dr. James Muller, co-director of the vulnerable plaque program of CIMIT, the hospital’s center for integration of medicine and innovative technology.
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 routinely used to gauge the degree of inflammatory response in everything from pneumonia to rheumatoid arthritis.
But the new, high sensitive cardiac CRP tests, sublicensed through Dade Behring in Deerfield, Ill., measure 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.)
Moreover, CRP is not just a marker of inflammation, but a bad actor directly involved in the in process of inflammation in plaques, notes Dr. Richard Pasternak, director of preventive cardiology at MGH.
That suggests that lowering CRP may directly lower the risk of cardiovascular disease. Indeed, with statin drugs (Lipitor, Pravachol, Lescol, Zocor and Mevacor), already used to lower cholesterol may be prescribed to lower CRP as well.
There’s already “an overwhelming abundance of data that statin drugs lower CRP levels,” says Dr. Karol Watson, co-director of the preventive cardiology program at the University of California, Los Angeles. In fact, one study, published in August in the Circulation, the journal of the American Heart Association, showed that such drug, simvastatin, lowers CRP levels very quickly – in just two weeks.
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, as Ridker is the first to note.
Compelling as the new data may be, it does not address whether treating people on the basis of high CRP test results is justified, notes Dr. Christopher O’Donnell, associate director of the Framingham Heart Study, a research effort sponsored by the National Heart Lung and Blood Institute..
Indeed, statins, though generally safe, can cause liver and muscle damage. One statin, Baycol (cerivastatin), was voluntarily taken off the market last year because it was associated with 31 fatal cases of a kind of muscle damage called rhabdomyolysis.
In other words, 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. At the very least, it makes sense to ask your doctor about it.