Apr. 23, 2001 DALLAS, April 17 – New research shows that three major statin drugs have similar anti-inflammatory effects, a key factor in atherosclerosis, according to a study in today’s Circulation: Journal of the American Heart Association.
Statin drugs lower cholesterol and previous research indicated that the statin – pravastatin – could reduce blood levels of C-reactive protein (CRP), a protein associated with the severe arterial inflammation that leads to heart attacks and strokes. New research finds that other statins – simvastatin and atorvastatin – can also reduce CRP.
"This is the first study where all three statin drugs were used in the same patients and their results compared," says Ishwarlal Jialal, M.D., Ph.D., director of the division of clinical biochemistry and human metabolism at the University of Texas Southwestern Medical Center at Dallas. "We found that 70 percent to 80 percent of patients who took any of these statins lowered their CRP to below 2.0 milligrams per liter, the critical level at which the risk of heart attack or stroke increases dramatically."
The randomized, double-blind study involved 22 individuals, average age 48, with elevated LDL or "bad" cholesterol and high triglyercides. Subjects followed the American Heart Association Step 1 diet (low-fat) and were given the three drugs alternately for periods of six weeks. Blood samples were taken three times at the beginning of the study and twice after each six-week period.
The CRP levels were reduced in 73 percent of subjects while taking pravastatin and 82 percent while taking simvastatin or atorvastatin. The average CRP reductions were 20 percent, 23 percent and 28 percent respectively.
CRP is known to be a major marker for any type of inflammation in the body, including pneumonia, tonsillitis and arthritis. There is evidence that elevated CRP also may be an independent risk factor for the arterial inflammation of atherosclerosis.
Jialal notes that CRP levels of less than 10 milligrams per liter (mg/L) are considered "normal" by present medical standards. "Yet several studies have shown that, in order to achieve a very low risk of cardiovascular disease, the CRP level must be below 0.7 mg/L," he says. "At levels of just 2.0 mg/L or above, the risk doubles or triples using the high sensitive assay which is now available in most academic medical centers.
"The good thing about all three statin drugs is that they lower CRP at the same time that they lower LDL and triglycerides," Jialal concludes. "This is probably why they are associated with lower mortality from heart attacks and strokes."
This study for the first time shows that there is a significant correlation between reduction in CRP and triglyceride levels. There is no correlation between reducing LDL cholesterol and reducing CRP, Jialal emphasizes. A person with normal LDL may still be at risk from elevated CRP and vice-versa.
Researchers explored the mechanism for the reduction in CRP with statins by measuring the main stimulus for CRP production in the liver, the pro-inflammatory agent, interleukin-6. But results showed that interleukin-6 levels were not significantly reduced by any of the drugs.
Jialal acknowledges that because of the study’s small sample size, these findings should be viewed with caution and further study is needed.
Other researchers include Daniel Stein, M.D.; David Balis, M.D.; Scott Grundy, M.D., Ph.D.; Beverly Adams-Huet, M.S.; and Sridevi Devaraj, Ph.D.
The research was funded in part by the National Institutes of Health.
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