CRP and Heart Attack Risk

It is now scientifically well established that inflammation in the arteries plays a role in the growth of atherosclerotic plaques. Inflammation also promotes blood clot formation.1 The rupture of unstable, cholesterol-filled plaques triggers the formation of a blood clot inside the artery. This clot can suddenly block blood flow to tissues, causing heart attack or stroke.

There is growing interest about using blood testing for chronic low levels of inflammation such as C-Reactive Protein (CRP) to determine a person’s future risk of having a heart attack. Current National Cholesterol Education Program (NCEP) guidelines for assessing the future risk for cardiovascular disease put the emphasis on LDL levels based on data from the Framingham Heart Study and do not recommend the use of CRP measurement.

A recent large prospective study of 27,939 women age 45 and older examined the risk for a first-time cardiovascular disease event (e.g., heart attack or stroke) over an eight-year follow-up period. At the start of the study, both LDL and CRP levels were measured. The women with either higher levels of CRP or higher levels of LDL were shown to be much more likely to suffer a first cardiovascular event than the women who had the lowest levels of these two substances in the blood. Indeed, the women with higher levels of CRP were actually somewhat more likely to experience a heart attack or stroke than those with the higher levels of LDL compared to those with the lowest levels.2 However, data from the Framingham Heart Study found that the association between higher CRP levels and having neck (carotid) arteries blocked by atherosclerotic plaque was significant in women but not in men.3

Should doctors start screening their patients for CRP levels?

Before CRP becomes a widely accepted test for screening individual patients for their risk of cardiovascular disease, it must be of proven value. CRP still has a ways to go before it is widely accepted as an effective screening tool.

One problem with CRP is that levels vary a lot more than do LDL levels when measured repeatedly in the same patient. This occurs even though no significant changes were made for diet, exercise or medications. CRP levels can also increase with infections or inflammatory conditions such as arthritis.

Studies of apparently healthy people have found CRP levels vary at least 4 to 5 times as much as do LDL levels.4 Another study found that CRP levels measured repeatedly in the same individual varied on average by 42%. By contrast, the variability in repeated LDL levels is less than 10%.5

Some of this variability is due to measurement error and some to real variation. If someone with a high-risk LDL level of 190 were measured a week later the chances are the next reading would be more than 170 and less than 210 and most of the time between 180 and 200. All these values suggest high risk or very high risk of atherosclerosis and a much greater risk of a heart attack in the next 5 years or so.

What if LDL levels varied by 42% on average? Then a 190 level one day could easily be as low as 110 the next week even though no changes were made in diet, lifestyle or medication. This would be unacceptable for clinical use because 110 suggests below average risk and 190 suggests very high risk.

Another problem with using CRP is that we have no evidence that lowering CRP levels with diet or drugs will lead to reduced heart attacks and strokes. We know this is the case if LDL levels are lowered with diet and/or drugs.

Based on current research, measuring the CRP level in the individual patient has not been proven to be sufficiently accurate, reliable or beneficial in terms of preventing cardiovascular disease.6

On the other hand, LDL levels and CRP levels do not correlate that closely. There are about 25-30 million Americans who may be at increased risk for cardiovascular disease despite below-average LDL levels because of more inflammation in their arteries. The CRP test would be of some value in helping to identify those people.

Bottom Line:

Using the CRP test in addition to LDL and other better-established risk factors may help identify those at increased risk of heart attacks and strokes. A diet low in both saturated fat and cholesterol with more fish, whole grains, fruits and vegetables, along with regular aerobic exercise, helps lower both LDL and CRP levels. There is no harm in recommending these healthful lifestyle changes to someone with a low LDL and high CRP level.

However, while cholesterol-lowering statin drugs lower both LDL and CRP levels they are not without risk or costs, so it is reasonable to withhold these drugs from the treatment of people who have high CRP levels but low LDL levels until future research establishes a clinical benefit at a reasonable cost of treatment.

See the full text article and corresponding 1-hour CPE course for CRP online at www.foodandhealth.com.

By Dr. James J. Kenney, PhD, RD, FACN.

References

1. Circulation. 2002;105:1135-43

2. N Engl J Med. 2002;347:1557-65

3. Arteriscler Thromb Vasc Biol 2002;22:1662-7

4. Am J Epidemiol 1999:149:261-7

5. Clin Chem 1997;43:52-8

6. Arch Intern Med 2002;162:867-9

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