Slow Death Without Fever

It has been called the secret disease because the progression is slow, steady and silent. Gradually, over a period of many years, atherosclerosis chokes off the flow of life-sustaining blood. The disease, resulting from the buildup of fibrous material, or plaque, in the arteries, has been killing people for centuries. Scientists have found plaque in the arteries of an Egyptian mummy dating from approximately 100 B.C. Leonardo da Vinci described atherosclerosis in his Dell'Anatomia, identifying it as the cause of a "slow death without any fever" that afflicts the elderly. It was not until this century that scientists began to realize that this disease of advancing age actually begins in youth, especially in cultures where the diet is rich. More than 77% of the American soldiers killed in the Korean War were found in autopsies to have blood vessels narrowed by atherosclerosis. Their average age: 22. The arteries of the young soldiers in the opposing forces--Koreans raised on a diet of rice and vegetables--showed no such damage. In regions where famine is rife and meat is scarce, cardiovascular disease is virtually unknown.

Scientists are not yet certain why high levels of cholesterol lead to heart disease or what sets the insidious process in motion. The most widely accepted explanation is the so-called injury theory, propounded by Russell Ross at the University of Washington in Seattle. According to Ross, the disease begins with damage to the thin layer of cells, or endothelium, that forms the protective lining of the arteries. In some cases, says Seattle Pathologist Earl Benditt, the lining may be harmed by viral infection. He has detected the presence of herpes virus in about 8% of atherosclerotic tissue samples. Damage can also result from high blood pressure, which forces blood to strike the artery wall with unusual force; from chemical derivatives of cigarette smoke; from elevated levels of blood fats; or simply from the turbulence of onrushing blood. This turbulence is greatest at the points where arteries divide into branches, explains Dr. Daniel Steinberg of the University of California at San Diego. And it is at these junctions that damage generally begins.

Injury to a healthy artery lining would be swiftly repaired. But this is not the case with atherosclerosis. Again, all the usual suspects--smoking, high blood pressure, elevated cholesterol levels--appear to interfere with the normal healing process. As a result, instead of arteries being repaired, a cycle of destruction begins.

The trigger is an elaborate exchange of signals among many types of cells that congregate in a sort of traffic jam at the site of the injury. Small blood cells, called platelets, may be the first to arrive. They release chemical messages that somehow cause smooth muscle cells, normally located below the endothelium, to migrate to the damaged area. These multiply wildly and produce a tangle of elastic fibers and connective tissue. Large white blood cells, called macrophages, add to the chaos by rushing in, in some cases even before the platelets, and filling up with cholesterol from the blood. The resulting "foam cells," Dr. Robert Mahley of the University of California at San Francisco explained to TIME'S Dick Thompson, "become so engorged that they burst, releasing their cholesterol and calling in more macrophages to clean it up." These in turn become distended and then burst, and so on. The proliferating mass gradually comes to resemble a lumpy scar.

According to Dr. David Blankenhorn, director of atherosclerosis research at the University of Southern California, the plaque may cease to develop or even shrink in size when cholesterol levels in the blood are reduced through diet or drugs. More often, however, the continued insults of rich foods, smoking and lack of exercise will, over a period of decades, lead to a gradual increase in the size of the plaque.

Finally, the flow of blood may become obstructed. If the affected vessel is a coronary artery, the victim is first likely to feel chest pains; if the vessel becomes completely blocked, he will have a heart attack. If, on the other hand, the blocked artery is one that delivers blood to the brain, the outcome will be a stroke.

Often there are no warning signs. "You don't sense your cholesterol rising or feel plaque developing," says Columbia University Cardiologist Robert Levy. For up to one-third of victims, the first sign of this secret disease is sudden death.