The research also found that for every 10 percentage points that cholesterol is reduced, the risk of death from coronary heart disease decreased by 15 percent, and total death risk by 11 percent.

"Our study is the first to establish a significant relationship between the degree of cholesterol reduction in total death risk," says A. Lawrence Gould, Ph.D., senior statistical scientist at Merck Research Laboratories, West Point, Pa.

Cholesterol is a fatty substance that can accumulate inside the blood vessels, causing obstructions that block blood flow, setting the stage for a heart attack or stroke.

Statins are a class of drugs that interfere with some of the cholesterol-producing metabolic pathways in the liver. Previous research of three of these drugs -- lovastatin, simvastatin and pravastatin -- has shown that they reduce cholesterol far more effectively than previously available drugs.

"These statins reduce lipids better than other interventions such as diet, other drugs and surgery," says Gould.

In 1995 the same group of researchers from Merck & Co., Inc., the National Institutes of Health and Bowman Gray School of Medicine, using meta-analysis techniques, published the first research demonstrating a significant relationship between lipid/cholesterol reduction and death from all causes. Meta-analysis techniques involve statistically synthesizing research results from several different studies to detect overall conclusions.

The 30 studies in that research did not involve the statins, however, says Gould. But the researchers wanted to see if the relationship between cholesterol reduction and death rates continued at the same pace for the statins, even with the much greater reduction in cholesterol that the drugs produced.

Between 1995 and 1997, results became available from eight clinical trials involving lovastatin, simvastatin and pravastatin.

"The question was: What can you say about the degree of risk reduction when you have blood cholesterol lowered by 20-30 percent? Is there a plateau? Do you gain as you go further down?" Gould says.

Researchers found no plateau with the statins included in the meta-analysis, he says. Death rates from any cause and death rates from coronary heart disease continued to decrease as cholesterol levels went down at the same rates as found by the earlier meta-analysis. The results were almost exactly what would have been predicted in the earlier study.

"There are some limitations to the conclusions," says Gould. "The fact that no plateau was found with the achievement of lowered cholesterol levels does not mean that a plateau might not occur at higher levels of cholesterol reduction. Also, the conclusions apply only to the statins included in the eight trials and may or may not apply to other statins where corresponding trial results are not yet available."

Further, not only did the statins used in these trials pose no additional risk of death from non-coronary heart disease causes, but the effect on cardiovascular death rates was large enough to have a significant effect on the total death rate, including causes other than heart disease.

"The reduction in death really comes from a reduction in cardiovascular mortality," says Gould. "But that is so profound a reduction that it in fact reduces the risk of mortality from any cause."

The study co-authors were Jacques E. Rossouw, M.D., from NIH, Nancy C. Santanello, M.S., M.D. and Joseph F. Heyse, Ph.D., also from Merck, and Curt D. Furberg, M.D., from Bowman Gray Medical School, Winston-Salem, N.C.

Note: If no author is given, the source is cited instead.

• Cholesterol
• Heart Disease
• Stroke Prevention
• Lung Disease
• Diseases and Conditions
• Triglycerides

• Low density lipoprotein
• High density lipoprotein
• Hypercholesterolemia
• Ischaemic heart disease
• Saturated fat
• Coronary heart disease