How does inflammation relate to heart disease and stroke risk?

"Inflammation" is the process by which the body responds to injury. Laboratory evidence and findings from autopsy studies suggest that the inflammatory process plays an important part in atherosclerosis (ath"er-o-skleh-RO'sis). That's the process in which fatty deposits build up in the lining of arteries.

C-reactive protein (CRP) is a protein in the body whose level increases when there's inflammation of blood vessels. It's been suggested that CRP may provide a new way to assess cardiovascular disease risk.

Researchers have found that blood levels of CRP are elevated many years before a first heart attack or stroke. One important study was published in the April 3, 1997, New England Journal of Medicine.

Using a test called high-sensitivity testing for CRP, the researchers measured baseline levels of CRP among 1,086 apparently healthy men participating in the Physicians' Health Study. These men were then followed over an eight-year period for future development of their first heart attack, stroke or venous thrombosis (blood clot in a vein).

What is the role of C-reactive protein in predicting risk?

Overall, the researchers found that men with the highest levels of C-reactive protein, compared to men with lower levels of the protein,

• have a threefold increase in their risk of heart attack.
   
• have a twofold increase in their risk of stroke.

These risks were independent of other traditional risk factors, including high blood cholesterol, smoking, high blood pressure and obesity.

Moreover, elevated levels of CRP were found to predict risk of first heart attacks as many as six to eight years in advance. That's enough time for someone to begin an aggressive program of prevention.

It appears that measuring C-reactive protein may provide a new way to detect worrisome levels of atherosclerosis in otherwise healthy people. These findings are important, because they raise the possibility that atherosclerosis may be at least in part an inflammatory disease. Moreover, the data suggest that measuring the body's response to injury may provide new ways to prevent cardiovascular disease.

For example, in the same study, researchers found that the benefit of preventive aspirin therapy was greatest among those with the highest levels of inflammation. Since aspirin is an anti-inflammatory as well as a blood-thinning agent, these data suggest that other anti-inflammatory therapies may also help to prevent and treat heart disease.

In another study published in the March 23, 2000 New England Journal of Medicine, researchers found that, among women who had gone through menopause, those with the highest quartile of C-reactive protein levels were more than four times as likely to have cardiovascular disease as those with the lowest quartile. This finding remained significant after women’s cholesterol levels were taken into account.

What causes low-grade inflammation?

No one knows for sure what causes the low-grade inflammation that seems to put otherwise healthy people at risk. However, the new findings are consistent with the hypothesis that an infection -- possibly one caused by a bacteria or a virus -- might contribute to or even cause atherosclerosis.

Possible infectious bacteria include Chlamydia pneumoniae (klah-MID'e-ah nu-MO'ne-i) and Helicobacter pylori (HEL'ih-ko-bak"ter pi-LO'ri). Possible viral agents include herpes simplex virus and cytomegalovirus (si"to-meg"ah-lo-VI'rus). Thus, it may be that antimicrobial or antiviral therapies will someday become part of the arsenal of therapies used to prevent heart attacks.

This idea clearly needs to be tested in clinical trials. However, the notion that chronic infection can lead to unsuspected disease isn't foreign to most doctors. For example, bacterial infection with Helicobacter pylori is now known to be the major cause of stomach ulcers. The treatment for this condition now routinely includes antibiotic therapy.

Should I have my C-reactive protein level measured?

A high-sensitivity measurement for C-reactive protein using automatic immunonephelometer is now available in many hospitals and health centers. However, it's uncertain whether regular measurement of C-reactive protein significantly adds to our ability to predict risk of heart disease. The American Heart Association and the Centers for Disease Control and Prevention have held a consensus-building workshop and will publish a summary on whether C-reactive protein levels should be routinely tested to diagnose heart disease or to monitor progress of treatments. Other recommendations will also be included.

AHA Recommendation

Regardless of one's "inflammatory risk profile," cardiologists recommend these steps to all patients (and the general public):

• Stop smoking, and avoid other people's tobacco smoke.
• Keep your blood pressure in check.
• Eat a healthy diet low in saturated fat, cholesterol and sodium.
• Maintain an active lifestyle and a healthy weight.
• Manage diabetes, if you have it.

These simple approaches significantly reduce the risk of heart disease. It's likely that they will be even more important for those who finally prove to have an inflammatory factor in their overall risk profile.

Related AHA publications:

• Heart and Stroke Facts
• Targeting the Facts... heart disease, stroke and risks
• Controlling Your Risk Factors... heart attack and stroke
• Six Steps to a Healthier Heart
• Aspirin and Your Health