Inflammation Reduced After Just Two Weeks on Statin Drug

The cholesterol-lowering drug simvastatin reduces both cholesterol and an inflammation marker linked to heart disease within two weeks, according to a study in today's rapid access issue of Circulation: Journal of the American Heart Association.

"Simvastatin caused a tremendous drop in low-density lipoprotein (LDL) cholesterol in just seven days, as we had expected, and also significantly reduced highly sensitive C-reactive protein (hsCRP) levels in 14 days. That finding was new," says Robert H. Eckel, M.D., professor of medicine, physiology and biophysics at the University of Colorado Health Sciences Center in Denver and a co-author of the study.

"The speed with which simvastatin lowers hsCRP levels raises the question of whether statins may prove useful for the acute treatment of coronary events, much the way nitroglycerin is used in emergency rooms today," he says.

HsCRP is a marker of inflammation, and elevated levels are a risk factor for heart attack. Moreover, at the time of a heart attack, hsCRP levels increase dramatically. Recent research indicates that statins can significantly reduce hsCRP levels over time, but this is the first study to find a significant decrease in just two weeks, he says. Simvastatin and other statin drugs reduce cholesterol levels and the risk of heart disease events.

High hsCRP levels are associated with poor outcomes after a heart attack or procedures to open clogged arteries. "Perhaps we could reduce those complications by giving statins right after angioplasty in patients who otherwise did not meet the criteria for the drug," Eckel says.

In this study, 40 men and women with high LDL cholesterol were randomly assigned to one of two groups. One group received simvastatin for 14 days followed by placebo for 14 days; the other group received the placebo first, then simvastatin. The average LDL level in both groups, which was 162 milligrams/deciliter (mg/dL) at the start of the study, dropped 56 mg/dL by the seventh day of statin treatment, and a further 8 mg/dL by day 14. Their average hsCRP levels fell from 2.55 milligrams/liter (mg/L) to 1.60 mg/L by day 14. The drug's effect on inflammation was unrelated to its effect on cholesterol levels, indicating the drug may work through multiple mechanisms, says Eckel.

These results support those of earlier studies that found that statins appear to protect against first and recurrent heart attacks in patients with elevated hsCRP levels regardless of their cholesterol levels, he says.

Many researchers believe inflammation plays a role in heart attack and some forms of stroke, although the exact mechanism is still being debated. What seems clear is that inflammatory processes and heart disease often occur together, says Eckel.

Although this study looks at only one statin, it's likely that other drugs in the class have similar effects, he adds.

Recent guidelines from the National Cholesterol Education Program call hsCRP an emerging risk factor for cardiovascular disease, Eckel says. Testing for hsCRP levels is not standard practice, but it can be done fairly easily and cheaply.

"I wouldn't promote its use on the basis of one study, but the evidence for its usefulness is increasing over time," he says. "The results of this study may have important long-term clinical implications by changing the way physicians manage all patients, both in the acute setting and in prevention of cardiovascular disease events."

Co-authors include lead author Julie K. Plenge, M.D.; Teri L. Hernandez, R.N., B.S.N.; Kathleen M. Weil, R.N., M.S.S.; Paul Poirier, M.D.; Gary K. Grunwald, Ph.D.; and Santica M. Marcovina, Ph.D.

The study was funded in part by Merck & Co.