Nov. 14 (AP)--In a study that may change the way millions of people assess their risk of heart disease, Boston researchers have found that testing for a protein produced when arteries are inflamed is a more reliable way of predicting a person's chance of having a heart attack or stroke than measuring cholesterol levels. Doctors said the simple, inexpensive blood test could provide an early warning to millions of Americans who think their heart disease risk is low because they don't have elevated cholesterol levels. In fact, about half of the 1.5 million heart attacks each year strike people with low to normal cholesterol.
Researchers at Brigham and Women's Hospital found that in women with low cholesterol counts, high levels of C-reactive protein nearly doubled the risk of heart disease. Those people were at higher risk than people with the opposite combination -- high cholesterol levels but low C-reactive protein -- even though people with high cholesterol are the ones most likely to worry about their cardiac health.
While cholesterol monitoring is likely to remain a cornerstone of prevention, the study raises health concerns about an estimated 25 percent of the adult population with low or normal cholesterol and high C-reactive protein, said Dr. Paul Ridker, the lead author of the study published in today's New England Journal of Medicine.
"They are a very high-risk group who are completely missed by current screening. And those patients don't spend a lot of time talking about diet and exercise and smoking cessation," Ridker, a professor at Harvard Medical School and director of the hospital's Center for Cardiovascular Disease Prevention, said yesterday. "We are doing our patients a disservice."
The American Heart Association plans to discuss the findings at a special session on Sunday at its annual meeting, and will take them into account when it issues revised heart screening guidelines together with the federal Centers for Disease Control and Prevention sometime in the next few months.
The association stopped short of recommending widespread testing yesterday, but officials there called the large-scale Brigham and Women's study "compelling evidence" that inflammation plays an important role in heart disease. The group's chief scientific officer said the test stands out as the most promising among numerous new risk factors that have been proposed for evaluating cardiac risk.
"When we have a country where 50 percent of the population is overweight, more than 1 out of 4 are obese, roughly 1 out of 3 are still smoking cigarettes, a test that is able to predict additional risk -- even though [the patient's] cholesterol value is OK -- can be a very powerful motivating factor," said Dr. Sidney Smith, a professor of medicine at the University of North Carolina.
The researchers tracked about 27,000 women in their ongoing Women's Health Study, measuring their levels of low-density lipoprotein -- the "bad" cholesterol associated with heart risks -- and C-reactive protein. Over eight years, the women with the highest levels of cholesterol were twice as likely to suffer from heart disease than those with the lowest levels. But the increased risk for the women with the highest levels of C-reactive protein was more than fourfold.
C-reactive protein is produced in the liver when arteries are inflamed. Inflammation -- part of the body's response to injuries and infections -- is what makes a sprained ankle swell and causes redness and swelling during colds and allergic reactions.
Over the last 15 years, interest has surged in the role of inflammation in heart disease.
"Bad" cholesterol promotes the buildup of plaque in the arteries, but inflammation makes the plaque unstable, increasing the chance it will break off and form a blood clot that causes a heart attack or stroke.
Scientists still don't fully understand the relationship, but Ridker and others theorize that it's part of the way early humans evolved to resist infection and famine: Just as defenses against starvation now can lead to obesity and diabetes, our immune response may be overreacting to an apparent threat and causing heart attacks.
Previous studies by Ridker and others have found that statins, the drugs used to lower cholesterol, also lower C-reactive protein. The next step is to conduct a randomized trial to see if putting people with high C-reactive protein on statins leads to fewer heart attacks and strokes.
Some specialists, including Dr. Lori Mosca of Columbia University, who wrote an accompanying editorial in the journal, worry that it is premature to recommend a new test. But while other new tests such as MRI screening for blocked arteries are expensive and can lead to risky angioplasties, the test for C-reactive protein costs Medicare $16, about the same as cholesterol testing, said Nader Rifai, a coauthor and chief pathologist at Children's Hospital.
Ridker disclosed in the article that he is named as a coinventor on a patent the Brigham and Women's Hospital holds on a technique for interpreting the test. Such patents are sometimes hard to enforce; the test is produced generically by a range of companies. The researchers were funded by the National Institutes of Health and nonprofit foundations.
Some doctors already are using the tests on some patients, said Smith, of the heart association. He said randomized trials would be needed before putting massive numbers of patients on statins because of high C-reactive protein levels.
But he said some doctors would probably consider using the test to further motivate patients who have low cholesterol but are obese, smoke, or don't exercise.
(c) 2002, The Boston Globe. Distributed by Knight Ridder/Tribune Business News.
