Two New Studies Show Reduction in Both C-Reactive Protein and Cholesterol Required to Control Heart Disease
01/05/05 -- A new Cleveland Clinic study shows that intensive use of statins, or cholesterol-lowering medications, reduces the progression of plaque buildup in the coronary arteries by reducing C-reactive protein, a measure of inflammation in the arteries. A related analysis at Boston's Brigham and Women's Hospital demonstrates that lowering C-reactive protein levels with statins also reduces the risk of recurrent heart attack. Both studies will appear in the Jan. 6 New England Journal of Medicine.
"Although we have known for several years that elevated CRP was a risk factor for heart disease, until now we did not have evidence that targeting CRP could reduce disease burden," said cardiologist Steven Nissen, M.D., author of The Cleveland Clinic study. "These two trials strongly suggest that we should target statin therapy at reducing CRP, not just cholesterol."
The Cleveland Clinic study analyzed the results of the REVERSAL trial, initially published in March 2004, which randomly assigned patients to either an intensive, 80-mg treatment with atorvastatin or a moderate, 40-mg pravastatin regimen to reduce low-density lipoprotein (LDL) cholesterol. In the study, 502 patients underwent a procedure known as intravascular ultrasound, in which a small probe is inserted into the coronary arteries to measure plaque. After 18 months of therapy with statin drugs, this procedure was repeated to measure how much the disease had progressed. The REVERSAL trial found that intensive treatment with atorvastatin halted the progression of atherosclerosis, or plaque build-up in the arteries, while the moderate pravastatin treatment did not stop progression of the disease.
In the NEJM study appearing this week, Dr. Nissen and colleagues report that intensive therapy with atorvastatin reduced CRP levels 36 percent, while the more moderate pravastatin regimen reduced CRP by 5 percent. They also observed that the reductions in CRP were independent of the reduction in cholesterol levels, indicating that the reduction in inflammation produced by the statins was not merely a consequence of lower cholesterol levels. The study demonstrated that both CRP and LDL cholesterol were "independently and significantly" linked to the rate of disease progression.
"Everyone thought the greater benefit of intensive atorvastatin therapy resulted exclusively from the lower cholesterol levels achieved in that group," Dr. Nissen said. "As a result of this new analysis, we now know that the more intensively treated patients experienced a decrease in disease progression in large part because they had a greater reduction in inflammation as measured by decreased levels of CRP, not merely because of lower LDL cholesterol."
At Brigham and Women's Hospital, Paul Ridker, M.D., conducted a new analysis of the PROVE-IT trial, first published in April 2004, also establishing that the more intensive atorvastatin regimen produced greater reductions in both CRP and LDL levels. Dr. Ridker's study demonstrated that greater lowering in both CRP and LDL levels was strongly associated with a reduced rate of recurrent cardiac events. The risk of an adverse event was lowest in patients in whom both CRP and LDL were substantially reduced, compared to patients with lesser reductions in these two biomarkers.
Thus, both studies found that patients with above-average reductions in CRP and LDL showed greater benefits than patients with lesser reduction in these two biomarkers.
"These findings strongly suggest that we should target statin therapy at reducing CRP, not just cholesterol," Dr. Nissen said. Current guidelines suggest that physicians reduce LDL cholesterol levels to as low as 70 mg/dL, but do not address the issue of reducing CRP levels.
"Our data indicates that the full benefits of statin therapy are observed only if both LDL-cholesterol and CRP are reduced," Dr. Nissen concluded. "We must now begin to think of CRP as an accelerator of disease activity, not just a marker associated with high risk."
The Cleveland Clinic Foundation, located in Cleveland, Ohio, is a not-for- profit multispecialty academic medical center that integrates clinical and hospital care with research and education. The Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names The Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,200 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2003, patients came for treatment from every state and nearly 90 countries. The Cleveland Clinic website address is clevelandclinic.org .
Source: The Cleveland Clinic
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