Cholesterol Lowering Drugs Stall Disease Progression In People With Below-Average Blood Cholesterol Level

May 11, 1998

DALLAS, May 12 -- A drug used to reduce cholesterol levels in the blood can prevent atherosclerosis -- even in people with below-average blood cholesterol levels -- according to a report in today's Circulation: Journal of the American Heart Association.

Lowering blood cholesterol in people with high levels of this waxy substance reduces the progression of atherosclerosis -- the build-up of fats and biological debris in the tissue lining the inside of blood vessels. New Zealand scientists found that no matter how low a person's cholesterol reading is, lowering his or her cholesterol prevented further development of blood vessel deposits that block blood flow to the heart and cause a heart attack.

"We were able to demonstrate a profound effect on the atherosclerotic disease process," says lead author, Stephen MacMahon, Ph.D., associate professor of medicine at the University of Auckland. "These results suggest that cholesterol lowering is likely to reduce atherosclerotic progression in most people with coronary heart disease across a broad range of pretreatment cholesterol levels," Mac Mahon and his colleagues say in their journal report.

Of the 522 people in the study, 273 were assigned to take 40 milligrams daily of a cholesterol-lowering drug called pravastatin and 249 received a placebo (an inert substance). Both groups were put on low-fat diets. Participants' blood cholesterol readings ranged from 155 to 271 milligrams per deciliter (mg/dL) at the start of the study. Average levels were considered to be about 218 mg/dL; below-average was about 184 mg/dL; and above-average levels were about 253 mg/dL.

Each underwent an ultrasound B scan of one carotid artery, the major artery that feeds blood to the brain, before being randomly assigned to either the drug or placebo-treated group. The scan was repeated two and four years into the study. Ultrasound is a widely used noninvasive technique to measure atherosclerosis in the carotid arteries. The degree of narrowing in the carotids is an indication of the amount of atherosclerosis elsewhere in the body. From the scans, the researchers could measure the thickness of the carotid artery wall; an increase in artery thickness over time indicated an increase in atherosclerotic deposits. At the end of four years, 77 percent of the pravastatin and 78 percent of the placebo patients remained in the study. The New Zealand researchers found that the pravastatin group had average total cholesterol of about 39 mg/dL (19 percent) lower than the placebo group. The average increase in carotid artery thickness was 0.048 millimeters (0.00187 inch) in the placebo group and a decrease in thickness of 0.014 millimeters (0.00055 inch) in the pravastatin group. "There was clearly a major difference between the two groups," MacMahon says. "We showed that cholesterol lowering with pravastatin appeared to prevent the progression of atherosclerosis in the carotid artery."

The effect of treatment was the same for those with above-average levels as those with average or below-average levels, according to MacMahon.

The drug group also had 27 percent lower "bad" low-density lipoprotein cholesterol, which is involved in building up artery deposits, and a 19 percent lower apolipoprotein B, a protein associated with "bad" cholesterol. The drug group also had a 13 percent lower level of triglycerides, the chemical form of fat in most foods; four percent higher apolipoprotein A1, a protein that appears to increase heart attack risk; and four percent higher "good" high-density lipoprotein cholesterol, which carries cholesterol away from blood vessel walls.

Does this study indicate that lowering cholesterol with a low fat diet also will prevent atherosclerosis? "Certainly, we would hope that cholesterol lowering, by whatever means, would have a beneficial effect on the atherosclerosis. But the specific results that we have are for cholesterol lowering with pravastatin. I think it would probably be unwise to generalize much further beyond that," MacMahon says.

Pravastatin is one of a group of cholesterol-lowering drugs known as HMG-CoA reductase inhibitors. They work by interfering with the body's natural ability to make cholesterol.

The new findings have implications for treating patients with average or low cholesterol but who have an elevated risk of heart attack, the nation's leading cause of death, and stroke, the third leading cause of death and the leading cause of serious, long-term disability, he says.

The study was carried out in Auckland, using 522 participants from a larger study of New Zealand and Australian coronary heart disease patients called LIPID (Long-term Intervention with Pravastatin in Ischemic Disease). LIPID ended last summer after six years, a year earlier than planned, when it was found pravastatin lowered the risk of death without causing harm to patients.

MacMahon and his colleagues undertook the smaller study, known as the LIPID Atherosclerosis Substudy, to determine if reducing blood cholesterol in people with low or average levels would reduce the development of atherosclerosis. "At the time we started the study, there was great uncertainty about whether it would be beneficial to lower cholesterol in people who have average cholesterol," MacMahon says. "There really was very little evidence, and of course, most patients with coronary heart disease have cholesterol levels that are fairly average."

Co-authors of the paper are Norman Sharpe, M.D.; Greg Gamble, M.Sc.; Hamish Hart, M.B.; John Scott, M.D.; John Simes, M.D.; and Harvey White, D.Sc.

American Heart Association

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