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C-Reactive Protein Testing For Heart Disease

Posted by medconsumers on December 22, 2002

Should You Be Tested For C-Reactive Protein?
By Maryann Napoli

The revised view of heart disease got a boost recently. Over the last ten years, a research case has been building for the possibility that chronic inflammation within the coronary artery walls plays a strong role in the development of heart disease. This hypothesis received some support from a new study showing that inflammation is a better predictor of who will have a heart attack than high cholesterol (The New England Journal of Medicine, 11/14/02). Nearly 28,000 healthy women were tested and followed for eight years; those whose blood tests showed high levels of C-reactive protein (CRP), an indicator of inflammation, were twice as likely to have a heart attack or a stroke as the women with high levels of LDL cholesterol, also known as the “bad cholesterol.” Similar findings are showing up in an ongoing study of 22,000 men.

Media reporting of this study generally gave the impression that many doctors did not think people should seek CRP testing, though it is readily available. And the leading guidelines-setting organizations like the American Heart Association have yet to take an official position about whether the CRP test should become part of the standard battery of tests routinely administered to all adults. But a New York Times editorial was downright enthusiastic, “The test could be a boon, if not for every American then at least for all those whose weight, age, smoking or other factors make them wonder about their cardiovascular prospects.”

It would be premature to start screening all adults for CRP, according to Lori Mosca, MD, who is the Director of Preventive Cardiology at New York Presbyterian Hospital. “We don’t yet know how to use this information, even though we do know that statistically CRP has been shown to predict cardiovascular events-just like 300 other risk markers for heart disease.” Dr. Mosca wrote the editorial that accompanied the new study, entitled, C-Reactive Protein-to Screen or Not to Screen? “People are calling my office to ask, ‘should I have a stress test or an angiogram’ because their CRP is elevated. I think there’s a real risk that this information is going to be misused,” she warned in a telephone interview. “And until science can figure what to do with the information, I think that screening every American is not appropriate at this point.” What’s more, gingivitis, bronchitis and many other possibilities can raise CRP levels.

That view was seconded by David Atkins, MD, chief medical officer at the Center for Practice and Technology Assessment at the U.S. Agency for Heathcare Research & Quality. To Dr. Atkins, the known major risk factors for heart disease-high blood pressure, diabetes, smoking, being overweight or obese, high LDL, and a sedentary lifestyle-already allow doctors to do a good job at identifying the people who should be treated with drugs. “Taken together these risk factors can probably catch the large majority [of people headed for] heart attacks,” said Dr. Atkins in a telephone interview.

After doing a call-in show for National Public Radio, Dr. Mosca worried that people got the wrong impression from news reports. “Consumers might misinterpret this new study to mean that LDL cholesterol is not important because it has been shown statistically that CRP is a little bit better predictor,” she said. “Well, we can say the same thing about hundreds of other risk factors. But LDL reduction has been shown to reduce death and disability, and CRP reduction has not.”

But half of all heart attacks occur in people with normal cholesterol levels-doesn’t that suggest high cholesterol isn’t such an important risk factor? “The reason why so many people with heart disease have so-called normal cholesterol levels is that normal is too high in the U.S.,” answered Dr. Mosca. “If our LDLs were cut in half [to the level] they are in Asia, we wouldn’t have so much heart disease,” she emphasized. “There is virtually no heart disease in countries where the total cholesterol is less than 150.”

The point that cholesterol levels shouldn’t be viewed in isolation was underscored by Dr. Atkins. “People hear that half of all heart attacks occur in people with normal cholesterol levels and think ‘that could be me,’ but the reality is that many of those people have diabetes, they smoke, or have hypertension,” he explained. “Only a very small percentage of heart attacks occur in people who don’t have multiple cardiac risk factors.” Dr. Atkins is concerned that most doctors still focus too narrowly on elevated cholesterol levels, when they should step back and look at the big picture-that is, the full range of major established risk factors for heart disease-and then target the intensity of the therapy accordingly.

Statins are the cholesterol-lowering drugs of choice. Lipitor and Zocor, the two top-selling statins, accounted for $4.5 billion and $2.7 billion in retail sales, respectively, in 2001 and the largest increase in prescription drug sales for that year. Low-dose aspirin therapy is another, far less expensive, standard drug recommended for heart attack prevention. There’s pretty good evidence that both drugs are effective even in people without high cholesterol, explained Dr. Atkins. Aspirin’s anti-inflammatory effect may account-at least, in part-for its success as a heart attack preventive, and statins have an anti-inflammatory effect as well as a cholesterol-lowering effect.

Learning that a person has elevated CRP levels isn’t-in most cases-going to change the treatment plan once a doctor assesses the patient’s other risk factors. “If the person is at low risk, it is unlikely that the CRP results will change our recommendations to the patient, we would still recommend exercise, maintaining weight, avoiding smoking, eating well, etc.,” said Dr. Mosca.

“For the very high-risk individual, that is, the person with heart disease, we already know they should be on statin and aspirin therapy, unless it’s contraindicated,” she continued. “For the middle-risk individual, the decision to test should rest on whether or not the treatment is going to be altered by the results,” she continued. “I’ve certainly screened some patients for CRP when I’m on the border for using certain kinds of therapy–after I have got them as good as I can in terms of lifestyle.”

Dr. Mosca said that after the New England Journal of Medicine published her editorial advising against routinely screening all adults for CRP, she received many congratulatory calls and e-mails from cardiologists around the country. All are concerned that CRP testing will be used routinely before research proves its worth.

“Look at hormone therapy,” said Dr. Mosca, referring to the trial that was stopped last summer because the combination of estrogen and progestin was deleterious to the health of older women. “Hormones became the standard of care for the prevention of heart disease, and when the clinical trial showed that the drugs not only didn’t prevent heart disease but caused heart disease in some women, we still have doctors who refuse to believe the information. We need to wait for the clinical trials before we make general public health recommendations to screen every American.”

(December 2002)

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