Inflammation May Impair Heart as Much As Cholesterol
Washington Post

By Rob Stein Washington Post Staff Writer

Damping down inflammation in the body appears to be just as important for fighting heart disease as lowering cholesterol, according to a pair of new studies that provide the first direct evidence that curbing inflammation can independently protect the heart.

Patients who reduced inflammation were significantly less likely to have their heart disease get worse or to die from a heart attack, even if their cholesterol levels were already low, the studies found.

The results suggest that doctors should consider routinely monitoring inflammation in the same way they test cholesterol and take steps to reduce inflammation in patients with high levels, especially in those already at high risk, the researchers said.

The same steps that lower cholesterol -- a healthful diet, exercise, weight loss, quitting smoking, and cholesterol-lowering statin drugs -- can help reduce inflammation. In addition, researchers are studying new drugs that may specifically target inflammation.

"For the first time, we have hard clinical evidence that lowering inflammation lowers the risk of heart attack and stroke and cardiovascular disease," said Paul M. Ridker, a cardiologist at Brigham and Women's Hospital in Boston, who led one of the studies being published in today's New England Journal of Medicine. "The magnitude of the benefit is at least as large as the magnitude of the benefit from cholesterol reduction. This is a radical change in our thinking about heart disease prevention."

For years, doctors have thought coronary artery disease occurs primarily when high cholesterol causes fatty buildups called plaques inside the arteries that supply blood to the heart, like clogging a drain. The theory holds that arteries slowly narrow and eventually get blocked, often by a blood clot, causing a heart attack.

But in recent years evidence has accumulated that inflammation, a usually beneficial response by the immune system for fighting off infections and healing injuries, also plays a key role. Too much inflammation, perhaps from being overweight, having high cholesterol or suffering from a chronic low-level infection, appears to damage the lining of artery walls and contribute to the formation and rupture of plaques.

No one knows exactly how many Americans suffer from excess inflammation, which often produces no symptoms, but doctors can detect it by testing blood levels of a protein called C-reactive protein (CRP), which goes up and down as inflammation rises and falls. Some evidence suggests CRP may damage the lining of artery walls directly.

Other researchers called for more study before recommending routine testing and treatment of inflammation based on the new findings, but said the research provides powerful support for the new way of thinking about heart disease -- the nation's leading killer.

"These are very important findings -- they provide further evidence of the importance of inflammation in establishing risk in patients with known coronary heart disease," said Sidney Smith, of the University of North Carolina at Chapel Hill, speaking for the American Heart Association.

In the first study, Ridker and his colleagues gave 3,745 patients who had already suffered a heart attack or severe chest pain either normal doses of the statin Pravachol or high doses of another statin called Lipitor, and measured their CRP levels.

The widely used statins appear to reduce inflammation, leading scientists to speculate that at least some of their benefit stems from their anti-inflammatory powers. The new studies were aimed at teasing apart their separate effects on cholesterol and inflammation.

Those whose CRP levels dropped the lowest were the least likely to suffer or die from another heart attack, the researchers found. In fact, cutting CRP was just as important as cutting levels of LDL cholesterol, the so-called bad cholesterol, and those with low CRP levels did better regardless of whether their LDL was high or low. That indicates that CRP was an independent risk factor, the researchers said. The patients with the lowest risk had the lowest levels of both LDL and CRP.

The findings may explain why many patients with low cholesterol still suffer heart attacks, Ridker said.

"These data provide overwhelming confirmation for the role inflammation plays in heart disease independent of cholesterol," he said. "It's no longer enough to simply monitor cholesterol. If we want to do the best for our patients, we now need to measure both cholesterol and CRP."

The second study, led by cardiologist Steven E. Nissen of the Cleveland Clinic, involved 502 patients with heart disease, half of whom received moderate statin therapy while the other half got high doses. The researchers then examined the inside of their arteries with a special ultrasound technique and measured their CRP levels. The patients whose CRP levels dropped the most had the least progression of their heart disease, again independent of cholesterol levels.

"We saw a very, very strong relationship between the degree in reduction in CRP and the degree of disease progression," Nissen said. "It has the same magnitude of effect as LDL but had an additive effect. This is a very compelling finding."

Some other experts agreed.

"This is an amazing vindication of the concept that inflammation is related to atherosclerosis," said Peter Libby of Harvard Medical School. "I would change my practice based on these data."

But other researchers said it is too early to recommend routine CRP testing or increasing statin doses specifically to lower CRP.

"The paradigm is shifting, but it doesn't shift overnight. I think we need more proof," said David Gordon of the National Heart, Lung, and Blood Institute.

Mark Pepys of the Royal Free & University College Medical School in London was more skeptical:
"There's no good evidence that lowering CRP will lower the risk. The evidence is not there that you must measure CRP in everybody and give statins to people with normal cholesterol. There's just no evidence for that."

The studies being reported today were funded by Bristol-Myers Squibb, which makes Pravachol, and Pfizer Inc., which makes Lipitor.