Here's a startling stat that people tracking their numbers should know: Half of all heart-attack victims have perfectly normal cholesterol levels, and many have no risk factors at all. Experts have recently come to believe that one hidden culprit is chronic inflammation, which turns arteries into plaque magnets. But they haven't known whether treating it could actually protect the heart. A new landmark finding suggests that is the case.
If confirmed in further studies, the research, published in the current New England Journal of Medicine, could transform screening for heart disease. Nearly 18,000 people with normal cholesterol levels and no heart disease but high levels of inflammation (as measured by a marker called C-reactive protein) were randomly assigned to take either a cholesterol-lowering statin drug with anti-inflammatory effects or a placebo. The people taking a statin, for two to five years, had about a 50 percent lower risk of heart attack or stroke and a 20 percent lower risk of dying of any cause compared with those who took placebos. They also had a 46 percent lower rate of bypass surgeries and angioplasties. "These results are way beyond what we could have hoped for," says study leader Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital.
Benefits for all. Indeed, the so-called Jupiter trial was recently stopped a few years early, after independent reviewers wowed by the results concluded that it wouldn't be ethical to keep anyone on sugar pills. The benefits applied across the board, to women (ages 60 and over) and men (50 and over), to blacks and Hispanics as well as whites, and to both smokers and nonsmokers. "This study is very important and very well done," says David Siscovick, a professor of medicine and epidemiology and codirector of the Cardiovascular Health Research Unit at the University of Washington in Seattle. "My guess is that it will be looked at very carefully by physicians and those involved in helping make recommendations for clinical care."
Others are less enthusiastic. While 50 percent may sound like a huge drop, in absolute terms "risk was reduced just a little bit," says Lisa Schwartz, an associate professor of medicine at the Dartmouth Institute for Health Policy and Clinical Practice. Among the 8,901 people taking a placebo, 132 heart attacks and strokes occurred during the study, compared with 64 in the same-size statin group—a fairly modest reduction in risk from 1.5 percent to 0.72 percent. And while the total number of deaths from all causes was lowered, each group experienced 12 deaths due to heart attacks and strokes. "I would have expected fewer deaths in the statin group," says Schwartz.
What's not in doubt, cardiologists agree, is that inflammation poses danger to the heart. There's no longer any question that it's part of the atherosclerosis process, says Jacques Genest, professor of medicine and director of cardiology at McGill University. Normal inflammation is a good thing; it's the body's way to repair injuries and protect itself from foreign invaders. But too much, linked to such chronic ills as smoking, diabetes, and obesity, contributes not only to artery plaque but a bursting of this plaque, which can result in a stroke- or heart attack-inducing blood clot. And previous research has suggested that high levels of CRP raise the risk of heart attacks and strokes.
The Jupiter trial found that being on a statin cut high CRP levels by 37 percent—which, to Ridker, suggests that screening for CRP should be much more widely used in heart disease risk assessment. (He helped invent the test, called "high-sensitivity CRP," and receives royalties from its sale.) Still, Ridker concedes that concluding that lowering an elevated CRP level directly benefits the arteries would be based on faith, rather than evidence. The American Heart Association says this "hasn't yet been established" and recommends thehs-CRP test only for intermediate-risk patients—those whose age, gender, cholesterol levels, blood pressure, and smoking habits translate as a 10 to 20 percent risk of heart attack over the next 10 years. (About half of the Jupiter participants had less than a 10 percent heart disease risk.) "The study doesn't totally clarify the causal role of CRP in the development of cardiac events," says AHA's president, Timothy Gardner.