Always On
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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.”
Ridker is most interested in preventing heart attacks in people who have normal cholesterol and blood pressure. He thinks some or most of the people who go on to suffer heart attacks or strokes have slightly elevated hsCRP, and he wants to know whether statins, by calming inflammation, could help prevent such individuals from suffering a first heart attack. For the past five years, he has led a trial known as JUPITER—Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin—a randomized, placebo-controlled test of almost 18,000 people, to see whether putting those with high hsCRP levels but average cholesterol on a statin will lower their risk of having a heart attack or stroke. Depending on the trial results, which are expected to be presented this November, measuring and monitoring inflammation could be as important as tracking cholesterol. “The JUPITER study could revolutionize the way people approach cardiovascular risk reduction and evaluation,” says Roger Blumenthal, director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. “This is a tremendous step forward.”
Not everyone is so optimistic, however. Some, such as Kinlay and Mason Freeman, director of the lipid clinic at the Massachusetts General Hospital, think positive results from the JUPITER trial would need to be interpreted cautiously. Freeman believes statins indirectly treat inflammation by reducing cholesterol; he also contends that what JUPITER defines as “average” LDL is now being shown to be too high—and that if statins help those whose levels are average by JUPITER’s standards, it will be because the drugs primarily reduce LDL.
