A Better Way to Screen for Heart Disease?

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.

Video: The Dangers of Heart Disease

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.

One confounding factor in Jupiter, experts point out, is that the drug used to lower inflammation—rosuvastatin, manufactured by AstraZeneca (which funded the study)—also dramatically lowered levels of harmful LDL cholesterol. Siscovick says this leaves open the question of whether the benefits were largely due to the statin's cholesterol-lowering effects, even though participants' LDL levels weren't elevated. Schwartz concurs and wonders whether a drug that targets only inflammation, like aspirin, might have worked as well as a statin in people without obvious heart disease.

Still, given the edge that statins demonstrated over placebos, why not make CRP screening as routine as cholesterol and blood pressure checks? After all, Schwartz estimates that half of American adults would be flagged as having high levels, defined by the Jupiter study as more than 2 mg per liter of blood. Trouble is, she says, this could swell the ranks of people on statins by millions. The drugs are considered to be very safe, but they do have side effects, such as disabling muscle pain. In rare cases, they elevate liver enzymes and cause severe muscle deterioration and kidney malfunction. While the Jupiter trial didn't detect a significant increase in these problems, Ridker admits that the study size may not have been large enough to detect unusual complications. And for reasons that aren't clear, the people taking statins were slightly more likely to develop diabetes during the study than the placebo group.

As doctors and public-health experts tussle over whether to look for and treat inflammation more aggressively, ordinary folks can act now to make some inflammation-fighting lifestyle changes. The Jupiter participants, with a typical CRP level of 4 mg per liter, weren't exactly the picture of health: Most of them were overweight, and many had metabolic syndrome, a precursor of diabetes that is characterized by high blood-sugar levels, too much abdominal fat, and high blood pressure, for example. Some were smokers. If this sounds like you, you probably have increased inflammation, too. A growing body of evidence suggests approaches beyond statins also lower CRP levels:

Smoking cessation. Smoking is associated with higher levels of CRP and has been shown to harden arteries, aggravating the effects of inflammation. But the damage needn't be permanent: A 2007 study published in Hypertension revealed that within 10 years of quitting, former smokers' arteries look like those of people who've never smoked. On the other hand, middle-age smokers have about double the risk of dying from heart disease and strokes compared with nonsmokers.

Heart-healthy diet. Italian researchers have shown that CRP levels decreased by an average of 0.8 mg per liter over two years in obese premenopausal women who increased their activity and adopted a Mediterranean-style diet centered on fruits, vegetables, whole grains, nuts, and fish instead of red meat and processed foods. "An anti-inflammatory diet is about reducing saturated fat and trans fats and eating more foods rich in alpha-linolenic acid—like flax seed, walnuts, and canola oil—and omega-3 fats, which fight inflammation," says Evangeline Lausier, a staff physician at Duke Integrative Medicine. She frequently recommends this diet to patients reluctant to take statins. On the flip side, a study published last month in the journal Circulation found that the typical American fast-food diet increases heart attack risk by 30 percent.

Physical activity. While a single bout of strenuous exercise can temporarily increase inflammatory chemicals, your body reaps anti-inflammatory benefits from a regular fitness routine, says Stanley Hazen, head of preventive cardiology at the Cleveland Clinic. An ideal amount for a healthy individual is five days a week of steady exercise (brisk walking, swimming, biking) for 30 to 45 minutes, he says. Do, though, avoid the kind of workout that leaves you very sore; this causes a spike in inflammation as the body rushes to heal itself.

Healthy waist size. Women who have a waist measurement of over 35 inches and men of over 40 inches are likely to have high levels of inflammation, since excess abdominal fat cells churn out too many inflammatory chemicals. What's deceptive is that many of these individuals also have high levels of the "good" HDL cholesterol and wrongly think they're protected from heart disease, says UCLA cardiologist Karol Watson. Cutting-edge research is now finding that HDL, which normally mops up excess cholesterol from arteries, can actually promote inflammation and add to plaque growth in people who already have high levels of inflammation. Whittling a few inches off the waist can go a long way toward solving that problem.

Adequate sleep. Poor sleeping habits appear to increase levels of inflammatory chemicals. A recent Duke University study found that women who took longer than 30 minutes to fall asleep had higher levels of CRP and another inflammation marker called interleukin-6 compared with those who fell asleep right away. And a May study published in the journal Sleep found that getting less than six hours a night doubles the risk of metabolic syndrome; it also found that sleeping too much—more than eight hours—resulted in more inflammation. The American Academy of Sleep Medicine says most adults need between seven and eight hours of shut-eye a night.

Less stress. Since high levels of stress hormones can trigger an excessive inflammatory response, try to work in a daily 15 minutes of relaxation—deep breathing, meditation, or a lovely foot massage.