Inflammation information

(This article was first printed in the July 2005 issue of the Harvard Health Letter. For more information or to order, please go to www.health.harvard.edu/health.)

Testing for C-reactive protein may be a good way to keep tabs on the inflammation that causes heart attacks.

Since the mid-1990s or so, researchers have changed the way they look at atherosclerosis. They used to regard it as a gradual buildup of fat- and cholesterol-filled plaques inside arteries. Now they see an inflammatory process that sometimes has a nasty, volcanic climax: A plaque ruptures, spilling its contents into the bloodstream, causing a potentially fatal traffic jam of blood clots and other factors.

This new view of atherosclerosis has doctors hunting for ways to detect inflammation early. So far, the strongest candidate is C-reactive protein (CRP).

A new predictor

Researchers used to think that CRP was made only in the liver. Now they know that it’s also made within the coronary arteries that carry blood to the heart. The test for measuring CRP produced in these coronary arteries is called a “high-sensitivity CRP” test — or hsCRP for short. Harvard-affiliated Brigham and Women’s Hospital has a patent on it. There’s now good evidence that high levels of hsCRP are indicative of future risk for heart attack and stroke in some people. In 2003, the American Heart Association endorsed the use of hsCRP for people at intermediate risk for heart attack. Patients and doctors who want to use a CRP test for cardiac risk prediction should ask for the high-sensitivity test because the older, standard CRP test doesn’t measure the protein in the low ranges relevant to cardiovascular disease.

Study results

But one of the nagging doubts about hsCRP has been whether it makes any difference to know your level if you’ve already had a heart attack or some other problem related to diseased coronary arteries. Why order another test? The doctor already knows you’re a high-risk patient. Two studies published in the Jan. 6, 2005, New England Journal of Medicine may help resolve these doubts.

Both dealt with patients being treated with statin drugs. In one study, patients who ended up with low LDL and CRP levels were less likely to have serious heart problems than those who had low LDL but high CRP (see chart). The results suggest that CRP levels do matter and that doctors may need to have two goals in treating heart attack patients with statins: getting the LDL below 70 mg/dL and the hsCRP level below 2.0 mg/L.

In the other study, researchers used ultrasound to measure the growth (“progression”) of atherosclerotic plaque among heart disease patients taking the same statin drugs. The researchers found a relationship between decreasing CRP and a slower progression of atherosclerosis. In fact, among those who had both low LDL and CRP, the plaque actually got smaller.

An important caveat: These studies enrolled people with diseased coronary arteries — they had had heart attacks or episodes of unstable angina, or an angiogram that showed significant narrowing. So how applicable the results are to people with healthier coronary arteries isn’t known yet.

Lowering CRP with diet and exercise

Several weight-loss studies have found favorable effects on CRP levels. Exercise also seems to be a CRP-reducer.

Harvard researchers have looked at CRP and seven risk factors for cardiovascular disease (high BMI, low HDL level, and so on). Based on associations found in a number of studies, they believe that the risk factors may have a cumulative effect on CRP levels: Having three gives you a higher CRP level than two; four gives you a higher level than three, and so on. They haven’t shown, though, that if you work to reduce those risk factors you’ll be rewarded with a lower CRP.

As for medications, the statin drugs do lower CRP levels, but not in everyone. So the hunt is on for the CRP-lowering pill. One possibility is the thiazolidinediones (TZDs), pioglitazone (ACTOS) and rosiglitazone (Avandia), which are used to treat insulin resistance in diabetics.

The bottom line

Universal CRP testing isn’t here yet. And the test is not a replacement for cholesterol testing but something to be used in addition. Remember, though, that half of all heart attacks and strokes occur among those with normal cholesterol levels, so knowing cholesterol may not be enough. The high-sensitivity CRP test may be particularly useful for people with metabolic syndrome, a condition that includes elevated blood glucose levels, high triglycerides, and several other risk factors, but not elevated LDL cholesterol. If you do get an hsCRP test and your level is high, we know that losing weight and exercising can help to lower it, proof once again that trimming down and keeping active is good for just about everything that ails us.

(This article was first printed in the July 2005 issue of the Harvard Health Letter. For more information or to order, please go to www.health.harvard.edu/health.)

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