Medicine: Coronaries & Cholesterol

On opposite sides of San Francisco Bay, two teams of University of California researchers hold different theories about the cause of hardening of the arteries. On the east side, in the Berkeley campus’ Donner Laboratory, Dr. John Gofman leans to the theory that giant cholesterol molecules are to blame (TIME, June 5, 1950). Now, from the University’s School of Medicine on the west side, comes strong evidence to the contrary. Cholesterol, according to Drs. Henry D. Moon and James F. Rinehart, does not cause hardening of the arteries, and is not even much of a factor until the disease is well advanced.

Moon and Rinehart went to work on the problem five years ago. It was all very well, they thought, to examine the main arteries of patients who had died of coronary attacks and note that there was a lot of cholesterol (a fatty alcohol) in the thickened walls. But, they argued, this was not proof that cholesterol was the cause of the thickening. They wanted to see what went on in the coronary arteries of normal people, as well as the victims of heart attacks. So the two pathologists arranged to get parts of arteries from the post-mortem examinations of people who had died suddenly. In five years, they got artery samples from 250 individuals ranging in age from four months to 90 years. Some had died of heart attacks, others in accidents. Their findings:

Protein Comes First. Early changes in the arteries (i.e., those often found in the coronary vessels of youngsters) do not involve cholesterol. First to appear is a slight thickening of the innermost layer of the arterial tubing. This stage is marked by an increase in the amount of mucoprotein (sugar protein), by fibrous growths of long, flat cells, and by breaks in the elastic tissue fibers. At this stage there is usually no cholesterol or other fat in the artery walls.

The second stage is marked by a further accumulation of sugar protein and the formation of hard, fibrous plaques in the walls, and fat (sometimes cholesterol) is always present. Finally, in far-advanced arteriosclerosis, parts of the artery wall become hard and glassy looking. Often there are deposits of calcium. And large globules of fat (including cholesterol) help to narrow the arterial tube so that the blood slows down and may form a dangerous or fatal clot.

Fat Comes First. In trying to find the cause of hardening of the arteries, which is a major factor in 350,000 U.S. deaths each year, doctors have been paying a lot of attention to fats like cholesterol. To Drs. Moon and Rinehart, this looks like the wrong path. Their theory is that fat metabolism becomes important only in the later stages of the disease, and that the original trouble probably lies in how the body uses protein.

Dr. Gofman is not impressed. “I still think the lipid [fat] process comes first,” he says. “If at any. given time you look at an artery that has been damaged by arteriosclerosis and find no signs of lipid substance, the tendency is to conclude that no lipid has existed. But there is strong evidence for believing that the lipid may have come first, starting the process, and then disappeared.”

In their efforts to prove or disprove the role of cholesterol, the two U. of C. research teams may be busy for years.