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Vol. 66, No. 1

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Q&A: New Test for Hearts at Risk?

After months of speculation about the diagnostic value of a new blood test to help identify those at risk of heart attack, a national panel led by a Medical Center researcher recommends limited use of the test. By Laurie Tarkan

A panel of experts has recommended that tens of thousands of people be tested for a new indicator of heart disease. The indicator, C-reactive protein, is produced in the liver in response to injury or inflammation, and it can help identify people at higher risk for heart attack and stroke, including those with normal cholesterol.

But the panel, convened by the Centers for Disease Control and Prevention and the American Heart Association, stopped short of recommending the test for every adult and said that the test should not replace assessments of other risk factors, like cholesterol, high blood pressure, and diabetes.

People with a low risk of heart disease and those with a high risk will most likely not benefit from the test, called high sensitivity C-reactive protein, or hs-CRP, the panel says.

Thomas Pearson, senior associate dean for research at the Medical Center and professor of community and preventive medicine, who cochaired the panel, helps clarify the recommendations.

Why did an expert panel write guidelines for testing for a new indicator of heart disease, known as hs-CRP?
Our response to that question is, How could you not write guidelines? There’s been tremendous interest generated in the media about the ability of hs-CRP to predict heart disease, and as a consequence there are a lot of patients asking doctors to get it. We think hundreds of thousands of hs-CRPs were measured last year. Clearly a lot of tests are being ordered in people for whom it won’t make a difference, and likely there are people in whom it would make a difference who aren’t getting it.

Will you explain the role of CRP, or C-reactive protein, in the hardening of the arteries that can lead to heart attacks and stroke?
Atherosclerosis is thought to be due to an inflammatory response to arterial injury. The injury is caused by high blood pressure, cholesterol, smoking, and other risk factors. Inflammatory cells, along with cholesterol and fatty substances, form lesions, and these lesions get little rubbery scars that are prone to rupture. If one ruptures, a core of plaque that has the consistency of pudding sets up a clot in the artery, leading to a heart attack or stroke.

“If you look at the tests for markers available today, hs-CRP is the best we have, but it may not always be so.”

So where does C-reactive protein come into play regarding inflammation?
One response to the inflammation in the artery is the release of cytokines, which in turn trigger the liver to raise C-reactive protein levels in the blood.

Is C-reactive protein a unique marker for heart disease?
We’ve known for many years that a number of inflammatory markers predict coronary events. So this whole idea of markers of inflammation is not exceptionally new. But if you look at the tests for markers available today, hs-CRP is the best we have, but it may not always be so.

How is C-reactive protein different from other risk factors like cholesterol?
In our report, we made great care to differentiate between a risk factor and a risk marker. A risk factor, like high cholesterol, is associated with disease because it’s a cause of the disease. If you lower that factor, you will lower the risk of disease. A risk marker, hs-CRP, is predictive of the disease, but there’s no evidence to suggest it’s a cause. Lowering hs-CRP doesn’t necessarily mean you’ll lower your risk. It may come to pass that it’s also a risk factor, but there’s not enough scientific evidence to support that.

The hs-CRP is a fairly inexpensive test, so why not test every adult?
Labs are charging between $20 and $120, but that’s not the issue. That’s chump change compared to the cost and burden of the follow-up testing you would do.

According to your panel, who should be tested for hs-CRP?
Typically it’s people who are borderline high risk. First, a doctor would measure a patient’s major risk factors, like cholesterol, high blood pressure, smoking, diabetes, sex, and age. Then he’d calculate the patient’s 10-year risk of developing a heart attack or dying of heart disease. We have simple formulas we use for that. If the risk falls between 10 percent and 20 percent, you’re in a situation in which you don’t know whether to treat this person or not, so doing this test would help inform your decision.

Preventive Cardiology for All

Thomas Pearson, senior associate dean for clinical research at the Medical Center, also chaired a national panel that is urging
Americans of all ages, even children, to make lifestyle changes—quitting smoking, eating right, exercising regularly—that are proven to prevent heart disease before it starts.

The strategy for implementing the changes for the first time at the community level was outlined in a paper published in Circulation: Journal of the American Heart Association last winter.

The new guidelines are intended as a roadmap for schools, employers, civic leaders, policymakers, and others interested in combating heart disease and stroke, the No. 1 killers in the United States.

Here is a sampling of the recommendations:

• All schools and work sites should provide age-appropriate curricula, materials, and services to educate people on causes and early warning signs, and motivate and assist people to improve their lifestyles.

• School gym class should be required at least three times a week for K-12, with an emphasis on lifetime sports and activities.

• Schools should offer heart-healthy breakfasts and lunches; TV food advertising directed to youths should be limited to foods that meet health guidelines.

• All citizens should be assured access to screening, counseling, and referral services for cardiovascular disease.

• Communities should support farmers’ markets, gardens, convenient bike routes, safe, attractive, and affordable fitness facilities, and a smoke-free environment.

• Grocery stores and restaurants should increase their offerings of foods that meet nutritional guidelines, and promote or display selections low in saturated fat, sodium, and calories.

Previously, the association’s guidelines have focused on treatment strategies aimed at physicians and their patients who already have heart disease, or who have risk factors. But the new recommendations emphasize the social and environmental origins of heart disease, and attempt to reach people of all cultures and socioeconomic groups, and overcome language barriers and literacy gaps.

“Health care providers, teachers, community leaders, and employers all need to work together to ensure that the places where we live and work and play promote heart health,” says Pearson, who was the lead author of the recommendations. “We also need to continue to be politically active. Cardiovascular disease is our biggest health threat. Americans need to know about the problem, understand how to prevent it, and have access to appropriate health care.

“Everyone should be a preventive cardiologist.”

Can people figure out their own 10-year risk?
They can go to the American Heart Association’s Web site,, which has a risk assessment tool.

Can you give a sense of someone who has a 10 percent to 20 percent chance of developing a heart attack or dying of heart disease in the next 10 years?
Smoking gets you there very fast; or having two or three elevated risk factors, like high bad cholesterol, high blood pressure, and being an older male, which is a substantial number of Americans. If you’re obese, you probably have several risk factors, and that will get you into that category.

Why do you suggest not testing people for the heart disease indictor if their risk of having a heart attack in the next 10 years is less than 10 percent? Or those whose risk is greater than 20 percent?
We feel very strongly you shouldn’t test someone in whom you wouldn’t do anything different on the basis of the test. You wouldn’t do it in someone who has coronary disease, a previous heart attack or stroke or diabetes, as we’re going to treat these people aggressively no matter what the results of hs-CRP are. Similarly if you have a young person with few risk factors, you wouldn’t test him either, because you’re not going to do anything about it. If a young person had a 2 percent risk factor, and had a high hs-CRP, it would only bring his risk up to 4 percent, which is a level we still wouldn’t treat.

What is considered a high marker for heart disease based on hs-CRP?
Hs-CRP can be classified as low, average, and high risk. You do two tests, two weeks apart, and average the two numbers. A low score is less than one milligram per liter, average is one to three milligrams per liter, and greater than three milligrams per liter is considered high risk. It turns out that someone in the high risk group has twice the risk as those in the low risk group. People with average risk have 1.6 times the risk of those in the low risk group.

How do you treat a patient with high hs-CRP?
This is the problem. You don’t treat risk markers. You’re not treating hs-CRP. You go back and look at other risk factors, and when you see something on the high side, you treat that symptom. You look at the cholesterol level. If that’s high, we have a host of powerful drugs we can use. If the blood pressure is high, we treat that aggressively. If someone didn’t have any obvious risk factors, we might recommend weight reduction and exercise programs, or suggest taking 75 to 160 milligrams of aspirin.

If hs-CRP goes down, does that mean you’re reducing the injuries to the arteries, the inflammation and therefore the risk of heart attack?
One would hope so, but nobody knows what it means. No clinical study has tested the hypothesis that direct therapy of hs-CRP causes you a good outcome. If the test, though, causes you to take steps to lower cholesterol or lower blood pressure or reduce your weight, that would lower your overall risk of heart disease.

Copyright 2003 by The New York Times Co. Reprinted with permission.

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