- The Washington Times - Thursday, November 14, 2002

BOSTON A landmark study offers the strongest evidence yet that simmering, painless inflammation deep within the body is the single most powerful trigger of heart attacks worse even than high cholesterol.

The latest research is likely to encourage many doctors to make blood tests for inflammation part of standard physical exams for middle-aged people, especially those with other conditions that increase their risk of heart trouble.

The study, based on nearly 28,000 women, is by far the largest to look at inflammation's role, and it shows that those with high levels are twice as likely as those with high cholesterol to die from heart attacks and strokes.

During the past five years, research by Dr. Paul Ridker of Boston's Brigham and Women's Hospital has built the case for the "inflammation hypothesis." With his latest study, many believe the evidence is overwhelming that inflammation is a central factor in cardiovascular disease, the world's biggest killer.

"I don't think it's a hypothesis anymore. It's proven," said Dr. Eric Topol, chief of cardiology at the Cleveland Clinic.

Inflammation can be measured with a test that checks for C-reactive protein, or CRP, a chemical necessary for fighting injury and infection. The test typically costs between $25 and $50.

Diet and exercise can lower CRP dramatically. Cholesterol-lowering drugs called statins also reduce CRP, as do aspirin and some other medicines.

Doctors believe inflammation has many possible sources, including fat cells and from a misguided defense attempt by white blood cells to break down fatty buildup, or plaque, that lines blood vessels.

Inflammation is thought to weaken the fatty buildups, making them more likely to burst. A piece of plaque can then lead to a clot that can choke the blood flow and cause a heart attack.

Other inflammation triggers include high blood pressure, smoking and lingering low-level infections, such as chronic gum disease.

For the first time, Dr. Ridker's study establishes what level of CRP should be considered worrisome, so doctors can make sense of patients' readings. However, experts are still divided about which patients to test and how to treat them if their CRP readings are high.

Some, such as Dr. Richard Milani of the Ochsner Clinic in New Orleans, recommend a CRP check for virtually anyone getting a cholesterol test.

"If I have enough concern to check a patient's cholesterol, it seems naive not to include an inexpensive test that would give me even more information," he said.

Others are reluctant to test people at low outward risk.

Dr. Sidney Smith, research director of the American Heart Association, said CRP testing is likely to be most helpful in guiding the care of the 40 percent of U.S. adults already considered at intermediate risk of heart attacks because of other conditions, such as age, obesity and high blood pressure.

In March, the heart association and the Centers for Disease Control and Prevention held a meeting of 50 experts to review evidence and make recommendations on CRP testing. It has extended its deadline after learning last week of Dr. Ridker's latest results, which are being published in today's New England Journal of Medicine.

A skeptical editorial in the journal by Dr. Lori Mosca of Columbia University questioned the need for widespread testing, at least until more studies are done to show that lowering CRP saves lives.

Such studies are planned. Until then, Dr. Ridker said he believes a high CRP reading can help doctors convince people with low cholesterol that they still need to diet and exercise.

"The CRP test can predict risk 15 to 25 years in the future," Dr. Ridker said. "We have a long time to get our patients to change their lifestyles, and the change does not have to be huge modest exercise, modest weight loss and stop smoking."

However, Dr. Mosca said telling people they have low CRP may falsely reassure them they can continue their slothful living habits. "Why do we need a test to help us motivate patients to improve their lifestyles?" she asked.

She also worried that doctors will immediately put patients on drugs to lower CRP before there is proof this saves lives.

Dr. Ridker's latest study is based on an eight-year followup of 27,939 volunteers in the Women's Health Study. About half of heart attacks and strokes occurred in those with seemingly safe levels of LDL, the bad cholesterol.

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