When Paul Ridker began practicing medicine in the mid-1980s, many of these details of the progression of atherosclerosis were unknown, and even now, scientists don’t understand why atherosclerosis happens to people with low cholesterol or other risk factors. “Fifty percent of all heart attacks and strokes in the United States every year occur in people with normal or even low levels of cholesterol,” says Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and the Eugene Braunwald professor of medicine at Harvard Medical School. “Fifteen to twenty percent of heart attacks and strokes happen to people with no recognized cardiovascular risk factors—no high blood pressure, high cholesterol or diabetes, and they don’t smoke.” Could inflammation be the real problem?

In 1995 Ridker began examining 1,086 men in the Physicians’ Health Study to see whether future heart attack and stroke victims could be identified in advance by testing baseline levels of inflammation. He zeroed in on CRP (C-reactive protein), a blood protein that acts as a marker for generalized inflammation in the body. Attempting to correlate high-sensitivity CRP (hsCRP) with future risk of disease, he found that in healthy men with no indication of heart disease, even slightly elevated hsCRP predicted who was likely to suffer a stroke or heart attack eight years later. It was as good a predictor as cholesterol levels.

The following year, Ridker discovered that adding a test for hsCRP to cholesterol screenings in men helped determine who would have his first heart attack much more precisely than cholesterol readings alone. And in 2000 he found that in healthy postmenopausal women, hsCRP was a more accurate predictor of risk for heart attack and stroke than 11 other indicators, including total cholesterol and LDL.

Finally, in 2002, a test for hsCRP became available in doctors’ offices, and physicians learned that patients with levels higher than three milligrams per liter have twice the risk of heart disease as those with readings below one. “There have been probably 20 major studies, all of which demonstrate that if your hsCRP levels are elevated, this inflammation marker alone means you’re at higher future risk of suffering a heart attack or stroke, independent of all other risk factors,” Ridker says.

As important as it has been to identify a new, pervasive cardiovascular risk factor, there remains the question of what to do about it. For now, there are no widely accepted answers. That could change, with “every pharmaceutical company pouring money into finding ways to inhibit vascular inflammation,” Ridker says. But he and others have come to think that an old way to treat cardiovascular disease might work better. Statins dramatically cut cholesterol levels, but although they decrease the risk of heart attacks and strokes by as much as 38%, they limit blood vessel narrowing by only a few percentage points. That shouldn’t be enough to cause such a large reduction in heart attacks, and recent studies suggest statins may have another trick up their sleeve: soothing inflammation.

In 1998 Ridker and his colleagues published the results of a clinical trial showing that when inflammation levels were high, statins reduced not just cholesterol but also hsCRP—dramatically. Ridker found similar results in a 2005 trial, in which the chance of survival after a heart attack was highest when both cholesterol and hsCRP levels were reduced. A study by Scott Kinlay at the Boston VA Hospital and Brigham and Women’s Hospital found that statins also helped reduce the risk of stroke.

What is it about statins that soothes chronic inflammation? “There’s a huge debate,” Kinlay says. “It’s possible that statins are directly affecting the inflammatory cells—somehow muting their response—or working indirectly by sucking cholesterol out of the artery wall. Both effects would reduce inflammation.”