Cholesterol & CRP Link

Posted: Feb. 1, 2005

C-reactive protein (CRP) is a measure of inflammation in the arteries. Two new studies show that reducing both C-reactive protein and cholesterol are required to control heart disease.

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 CRP.

A related analysis at Boston’s Brigham and Women’s Hospital demonstrates that lowering CRP levels with statins also reduces the risk of recurrent heart attack. Both studies appeared in the Jan. 6, 2005, 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. After 18 months of therapy with statin drugs, 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.

CRP & LDL cholesterol
The intensive therapy with atorvastatin reduced CRP levels 36 percent, while the more moderate pravastatin regimen reduced CRP by 5 percent. 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.”

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