Howard Hodis

Researchers at USC’s Atherosclerosis Research Institute have shown for the first time that vitamin E, alone or in combination with cholesterol-lowering drugs, may slow and possibly reverse the formation of plaque in the coronary arteries. The study is published in the June 21 Journal of the American Medical Association (JAMA).

The patients studied were part of the USC Cholesterol Lowering Atherosclerosis Study (CLAS). CLAS investigators evaluated the narrowing in blood vessels of 162 non-smoking men aged 40 to 59 years who were then randomly selected to take vitamin E with either a placebo or the drug colestipol along with high doses of niacin. Changes in blood vessel narrowing were measured using angiograms at the beginning of the study and again after two years.

CLAS subjects also reported their intake of supplemental vitamins and those taking 100 international units per day or more of vitamin E showed significantly reduced narrowing of their arteries.

“Although further study is clearly needed, our findings strongly indicate that antioxidant vitamins, particularly vitamin E, may be effective in slowing the progression of atherosclerosis,” said Howard Hodis, M.D., USC assistant professor of cardiology and preventive medicine and director of the USC Atherosclerosis Research Unit. “These findings are exciting because vessel narrowing appeared to slow regardless of whether patients were taking the vitamin E and placebo or vitamin E and the cholesterol-lowering regimen.”

In the sequence of events that takes place in coronary artery disease, arteries accumulate plaque that eventually narrows them. The narrowing progresses until there is near or total blockage, resulting in myocardial infarction, or heart attack. Heart disease remains the leading cause of death in both men and women in the U.S.

“This is the first angiographic evidence to show antioxidant vitamins can reduce the progression of atherosclerosis,” said Hodis. “Furthermore, since progressive narrowing of coronary arteries is ultimately linked with heart attack and coronary artery-related death, our results provide a plausible explanation for the reductions in arterial narrowing seen in the group taking the vitamin E.”

The JAMA study was funded by the National Institutes of Health’s Heart, Lung and Blood Institute that last year awarded the USC School of Medicine a $4.8 million grant to study the effects of cholesterol reduction and hormone replace-ment therapy on heart disease in post-menopausal women.

One of the only trials in the U.S. to study the effect of these therapies on the progression of atherosclerosis, it includes researchers from the USC Menopause Center and Department of Preventive Medicine. USC researchers have been conducting atherosclerosis and menopause research for the last 20 years.

Coronary artery disease accounts for about 200,000 deaths each year. For reasons that are not yet understood, pre-menopausal women have an extremely low risk of dying from heart disease – yet 90 percent of atherosclerosis deaths occur after menopause.

“These trials will help us understand the mechanisms behind this observation,” said Hodis.

In a related study published in the July, 1994 edition of the American Heart Association journal, Circulation, Hodis and his group added to the line-up of culprits responsible for coronary artery blockages.

Fatty acid molecules called triglycerides, they found, are also involved in coronary artery disease. For years, medical scientists have debated just how important triglycerides are to the development of coronary artery disease – the precursor of heart attacks. Originating directly from fatty foods, and also from carbohydrates, triglycerides comprise much of the fat stored by the body.

Evidence of the role triglycerides play was shown when the known source of blockages, low-density lipoproteins (LDL) also known as “bad” cholesterol, was controlled in patients using the drug Lovastatin, yet the progression of their disease was not completely halted.

“These findings were the first to indicate that tryglyceride-rich lipoproteins have a pronounced effect on the progression of artery-clogging plaques,” said Hodis. “We observed that in patients whose LDL’s were controlled with Lovastatin, triglyceride-rich lipoproteins continued to cause the smaller plaques to progress. LDL’s had more effect on the growth of larger plaques.”

Triglyceride levels vary greatly because they are determined by genetics as well as the amount of fat in the patient’s last meal. For those reasons, researchers have, until now, been unable to draw firm conclusions from previous studies.

Study data was gathered from the Monitored Atherosclerosis Regression Study (MARS), a two-year trial of the drug Lovastatin that involved 270 subjects with plaques in at least two segments of their coronary arteries. The progression or regression of the subject’s plaques was measured with a computerized imaging system that precisely calculates changes.

“The next step in this research will be to see if lowering triglyceride levels in conjuction with Lowering LDLs will further slow the atherosclerotic process,” said Hodis. “We think this will be very important, especially for people with existing coronary artery disease.”

Future plans for Hodis and his group include follow-up studies specifically looking at the role of vitamin E and its potential benefits, trials of the cholesterol-lowering drugs Colestipol and Lovastatin, and analyzing the effects of estrogen on the hearts of post-menopausal women, all with the ultimate goal of deposing heart disease as the leading cause of death in both men and women in the U.S.