Jan 6 2005
Aggressive therapy with statins -- drugs that inhibit cholesterol synthesis -- works better than moderate statin therapy in reducing fats and proteins in the blood that have been linked to atherosclerosis, a new multi-center study concludes. Statins’ effects on both complex compounds appear beneficial in cutting patients’ cardiovascular risks.
Atherosclerosis is the progressive disease process, often called hardening of the arteries, in which blood vessels slowly narrow with brain- and heart-threatening plaque, something like rust blocking water flow in an iron pipe.
A report on the research appears in Thursday's (Jan. 6) issue of the New England Journal of Medicine.
More than three dozen investigators from across the country participated in the research, including first author Dr. Steven E. Nissen of the Cleveland Clinic Foundation and Dr. Sidney C. Smith Jr.
A past president of the American Heart Association, Smith is professor of medicine and director of the Center for Cardiovascular Science and Medicine at the University of North Carolina at Chapel Hill School of Medicine. He also served on the steering committee of a second, closely related investigation appearing in the same issue and led by Dr. Paul M. Ridker of Harvard Medical School and others.
Scientists designed the first study to investigate the relative contributions of statins in lowering fats in blood and also C-reactive protein (CRP), the most reliable laboratory measure of systemic inflammation in the body. It involved performing ultrasound tests on 502 U.S. patients with documented coronary artery disease.
Half the patients then received 40 milligrams of pravastatin, while the rest underwent the more aggressive treatment of 80 milligrams of atorvastatin. Doctors repeated the ultrasound evaluations 18 months later.
In the group as a whole, the mean LDL cholesterol level dropped from 150.2 milligrams per deciliter to 94.5 milligrams per deciliter. Both cholesterol and C-reactive protein levels correlated with progression of patients’ disease.
"Patients with reductions in both LDL cholesterol and C-reactive protein that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median," the authors wrote.
The second study involved 3,745 people. Patients who were found to have low C-reactive protein levels after treatment fared better than those with higher CRP levels, regardless of their post-therapy cholesterol level.
"Taken together, these two studies emphasize the importance of inflammation in patients with coronary heart disease and suggest that inflammatory markers such as CRP may be useful along with traditional risk factors such as LDL cholesterol in patient management," Smith said. "The question at this point is what further therapy or therapies might be most effective in such patients."
Results of prospective, randomized clinical trials could be helpful in resolving that question, he said. They also should contribute to important decisions about improving guideline recommendations.
"Patients who are on low-dose statin therapy may benefit by increases in their statin therapy," Smith said. "However, those already taking maximum doses of statin, as well as all patients with coronary heart disease, should know that smoking cessation, weight loss and exercise all are associated with improvements in CRP levels.
"These studies confirm the value of lipid lowering for patients with coronary heart disease and suggest that therapy targeted to reduce the active inflammatory state may carry additional benefits," he said.
Dr. Michael R. Ehrenstein and colleagues in the department of medicine at University College in London wrote an accompanying editorial.
The two articles confirm that reducing the inflammatory component of cardiovascular disease through use of statin therapy improves clinical outcomes independently of the reduction in serum cholesterol levels, the authors wrote.
"…The list of disorders for which statins might prove beneficial is growing and now extends from multiple sclerosis and neurodegenerative disorders to rheumatoid arthritis and systemic lupus erythematosus," they wrote.
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