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C-Reactive Protein

A blood marker for inflammation, which is thought to play a role in many chronic diseases, including heart disease, stroke, and diabetes. Scientific studies have shown not only that a high level of C-reactive protein (CRP) is a risk factor for heart disease and stroke, but also that lowering CRP levels can substantially lower a person’s risk of heart disease.

Inflammation is thought to promote the buildup of atherosclerotic plaque (deposits of fat and other materials in the lining of blood vessels). It may especially favor the buildup of so-called “vulnerable” plaques, which are prone to breaking and developing clots that can block arteries, leading to heart attack and stroke.

Years ago, the Physicians’ Health Study showed that men who had heart attacks and strokes over the 8 to 10 years of the study had higher levels of CRP than those who didn’t. Those with the highest CRP levels had three times the risk of a heart attack and twice the risk of a stroke as men with the lowest levels. A study reported in the journal Diabetes Care in 2004 showed similar effects in men with diabetes: Those in the highest quartile of CRP levels had nearly three times the risk of cardiovascular events (heart attack, bypass surgery, angioplasty, or stroke) as those in the lowest quartile.

Yet up until now, no one knew whether CRP really promoted heart disease or whether it was an “innocent bystander” — an innocuous marker of heart disease rather than a cause. That has begun to change with the publication of two landmark studies in the January 6, 2005, issue of The New England Journal of Medicine. One, by Paul M. Ridker, MD, and colleagues at Brigham and Women’s Hospital and Harvard Medical School in Boston, studied the effects of high doses of statin drugs, which lower cholesterol and CRP, in people with severe heart disease. They found that lower CRP levels were associated with fewer heart attacks and deaths, regardless of study subjects’ low-density lipoprotein (LDL, or “bad”) cholesterol levels. The other study, by Steven E. Nissen, MD, and colleagues at the Cleveland Clinic in Cleveland, Ohio, also looked at the effects of both moderate and intensive statin therapy in people with heart disease. They found that people getting intensive statin therapy had much slower progression of atherosclerosis and that those with lower CRP levels had slower progression, independent of cholesterol levels. In fact, lowering CRP levels appeared to be at least as important as lowering cholesterol in terms of preventing heart disease.

Inflammation may play a role in the development of diabetes as well. In the Cardiovascular Health Study, the quartile of people with the highest CRP levels were about twice as likely to develop diabetes within three to four years of the study than the quartile of people with the lowest levels of CRP. In fact, some researchers speculate that inflammation may be an underlying factor in both diabetes and atherosclerosis, which may help explain why people with diabetes are so much more prone to atherosclerosis, heart attack, and stroke.

Currently, guidelines from the American Heart Association and the Centers for Disease Control and Prevention recommend considering testing for CRP only for people at “intermediate risk” for heart disease. (Intermediate risk is having a 10% to 20% chance of having a heart attack in 10 years.) Risk factors for heart disease include being older than 45 (for men) or 55 (for women), smoking, being overweight, having high blood pressure, having high levels of LDL cholesterol and/or triglycerides (a blood fat), having low levels of high-density lipoprotein (HDL, or “good”) cholesterol, having a family history of heart attack or stroke, and having diabetes.

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