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Heart Attack Prevention

2004 Edition

C-Reactive Protein: A New Risk Factor for Heart Attack
A recent study shows that high levels of this protein may be a better predictor of heart attacks than high cholesterol levels. Should you be tested for it?

One of the key markers for measuring heart attack risk has been a high level of low density lipoprotein (LDL, or “bad”) cholesterol. Yet about half of the people who develop coronary heart disease (CHD) have normal or even low LDL levels. In the search for additional ways to predict the risk of CHD, considerable evidence indicates that a molecule called C-reactive protein (CRP)—a blood marker for excessive inflammation of the artery walls—tends to be elevated in people who go on to develop CHD and have a heart attack. While lowering cholesterol remains a primary goal in preventing heart attacks, it is possible that CRP may be slightly better than cholesterol (or at least comparable with cholesterol) at predicting a person’s risk for heart attack.

At first, researchers thought that CRP might just be associated with other risk factors for CHD, like smoking, high blood pressure, or high LDL cholesterol levels, rather than a causative factor. But a study published in January 2003 in Circulation shows that elevated CRP in the blood may directly contribute to the formation of blood clots that can cause heart attacks. Based on this and other studies, CRP appears to have a predictive value that is independent of other risk factors for CHD.

We do not know whether treatment to lower high CRP levels decreases the risk of heart attacks. But if future randomized trials show that this is the case, then measuring CRP—in addition to cholesterol levels and blood pressure—may become an established protocol of primary heart attack prevention.

What Is CRP?

The liver produces CRP when inflammation occurs anywhere in the body. Such inflammation can stem from a number of sources, not just within the walls of arteries, including gingivitis (gum disease), metabolic syndrome, high blood pressure, obesity, diabetes, and smoking. Inflammation is also a component of infections (such as the influenza virus or Helicobacter pylori—the bacterium that causes peptic ulcers) and of rheumatoid arthritis.

CRP levels above 3 mg/L (milligrams per liter) are considered elevated. Up to 50% of heart attack patients have elevated CRP levels, as do over 65% of unstable angina patients and over 90% of patients with unstable angina who’ve also had a heart attack. In people without CHD, high CRP levels are rare, occurring in less than 10%.

The Evidence

Some of the strongest evidence showing that CRP levels are independently related to the risk of heart attacks was published in November 2002 in The New England Journal of Medicine. Researchers measured LDL cholesterol and CRP levels in nearly 28,000 healthy women and followed them for an average of about 8 years, looking for evidence of cardiovascular disease.

Women with the highest CRP levels (over 4.2 mg/L) at the beginning of the study were 2.3 times more likely to develop cardiovascular disease than those with the lowest CRP levels (below 0.5 mg/L). Those with the highest LDL cholesterol levels (over 154 mg/dL), on the other hand, were only 1.5 times more likely to develop cardiovascular disease than those with the lowest LDL levels (below 98 mg/dL). Among women not using hormone replacement therapy at the study’s start, those with low LDL cholesterol but high CRP levels were slightly more likely to have cardiovascular disease by the end of the study than did women with low CRP but high LDL cholesterol levels. These data led the researchers to conclude that CRP “is a stronger predictor of future cardiovascular events than LDL cholesterol.”

Who Should Be Tested?

The test for CRP is easy for doctors to perform (it involves drawing blood from a vein in the arm) and costs only about $15 to $20. Does this mean everyone should get the test? According to guidelines jointly published by the American Heart Association (AHA) and Centers for Disease Control and Prevention (CDC) in January 2003 in Circulation, the people who will likely benefit from CRP testing are those with an intermediate risk of CHD—that is, a 10% to 20% risk of a heart attack in the next 10 years. (To determine your risk level, talk to your doctor or assess your risk at a Web site sponsored by the National Institutes of Health.

If you are found to be at intermediate risk for a heart attack, establishing that you have a high CRP level may indicate the need to begin a more intense CHD prevention program. You may also be more motivated to improve prevention efforts such as exercising more and eating a healthier diet.

People already at high risk for CHD and those receiving medication to prevent or treat CHD do not need or benefit from a CRP test, according to the AHA and CDC. Such people should already be aware of their overall elevated risk for CHD, and finding an elevated CRP level will not provide any additional information.

Getting Your Results

If you are at intermediate risk for CHD and decide to have a CRP test, the AHA and CDC suggest you average the results of two tests taken at least two weeks apart. Don’t begin treatment to lower CRP levels on the basis of one test, since test results can be affected by a flare-up of inflammation from arthritis or an infection. If you know you have an infection, postpone the test. Several versions of the test are available. Be sure to use the high sensitivity CRP (hs-CRP) version; this is the only one that can detect small differences in CRP that may translate into large differences in CHD risk.

The AHA/CDC report states that people who have a CRP level below 1 mg/L are at a low risk for cardiovascular events, while those with a CRP level from 1 to 3 mg/L are at intermediate risk.

The two organizations emphasize that the CRP test cannot replace an evaluation of other risk factors, and that an elevated CRP alone does not provide sufficient evidence to warrant starting drug therapy.

Treating High CRP Levels

Currently, no drug is specifically designed to lower elevated CRP levels, and no clinical trial has yet been conducted to show that lowering CRP directly causes a reduction in heart attacks. However, if you have a high CRP level, some of the measures that play a role in reducing other risk factors for CHD appear to also lower elevated CHD levels—and so could potentially decrease a person’s risk of heart attack even further.

Physical activity. A correlational study of 722 men published in the November 2002 issue of Arteriosclerosis, Thrombosis, and Vascular Biology found that the more men exercised, the lower their CRP levels were. While some preliminary data suggest that initiating a regular exercise program may cut CRP levels up to 35%, the type and intensity of exercise that may be necessary to reduce CRP is not yet established.

Weight control. If you are overweight, losing weight may also lower CRP levels. A February 2002 Circulation report found that, among 25 obese postmenopausal women who lost an average of 32 lbs., CRP levels also fell by 32%.

Aspirin. Aspirin not only reduces the likelihood of a blood clot, but also decreases inflammation. Talk to your doctor before taking aspirin for this purpose.

Statin drugs. Prescribed for lowering LDL cholesterol levels, statin drugs also lower CRP levels. In a 2001 New England Journal of Medicine study of 5,742 people with elevated CRP but normal LDL cholesterol levels, those who received lovastatin (Mevacor) reduced their CRP levels by 15%. They also experienced lower rates of heart attacks and other CHD events than participants who took a placebo. However, more definitive data are needed before physicians routinely prescribe statins to lower CRP in people with normal LDL cholesterol levels.

ACE inhibitors. Some research indicates that a group of blood pressure-lowering drugs called ACE inhibitors can also decrease CRP levels. More research is needed, however, before doctors begin to prescribe ACE inhibitors to lower CRP levels.


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