Filtering Out Killer Cholesterol

By Claudia Wallis

When "Jim Lewis," 58, arrived at the Rogosin Institute at New York Hospital one year ago, he was a desperate man. Lewis (not his real name) had been suffering from severe heart disease for most of his adult life. His condition was due largely to a genetic disorder that afflicts 1 in 500 Americans, causing abnormally high levels of cholesterol to accumulate in the blood and ultimately clog the arteries. In Lewis' case, the strictest low-fat diet and all the drugs that medicine could muster had failed to control the problem. By the time he was 47, his arteries were so blocked--a condition known as atherosclerosis--that he required quadruple-bypass surgery. Nine years later a double-bypass was performed. But in both instances the vessels that had been grafted around his heart became plugged with fatty plaque. When the second bypass failed, Lewis had run out of standard medical options. "I was in a dead-end situation," he recalls. "My doctor gave me less than a year to < live."

At the Rogosin Institute, Lewis became a guinea pig in an experimental treatment program. Once a week he would drive to the hospital to undergo a procedure called LDL-pheresis, a filtering process that removes from the blood the most dangerous form of cholesterol, known as LDL (for low-density lipoprotein). Now, after a year of treatments, Lewis is remarkably improved. His once crippling angina is "almost nonexistent," he reports. Thick deposits of cholesterol that used to be visible on his hands have largely vanished. He has resumed physical activity. "I'm walking half a mile in eight or nine minutes," he boasts. "It's a whole new ballgame. Now I have a future."

The procedure that has given Lewis a future somewhat resembles kidney dialysis. Patients undergoing LDL-pheresis sit or recline for three to four hours as their blood circulates through two specialized devices. The first separates blood cells from blood plasma; the second filters the plasma through a jar of porous beads coated with an antibody that traps LDL. The beauty of the procedure, says its developer, German Biochemist Wilhelm Stoffel, is that "the antibody picks out only LDL." Other important blood components, including a valuable form of cholesterol called HDL (high-density lipoprotein), are all returned to the patient. In fact, according to a study published this week by the Rogosin group, this "good" cholesterol actually rises in patients treated with LDL-pheresis.

So far the technique has been tried at only a handful of medical centers around the world and only on the most desperately ill patients. Stoffel, together with Dr. Helmut Borberg at the University of Cologne, is treating ten people, most of them with the same condition as Lewis', known to doctors as familial hypercholesterolemia, or FH. In Moscow, eminent Soviet Cardiologist Yevgeni Chazov is treating another ten FH patients, working closely with the Rogosin Institute in an unusual Soviet-American collaboration. Both overseas groups report that their patients' angina has decreased and that they perform better on stress tests.

Some of the most encouraging results have been in children with a rare and extreme version of FH. Yuko, 11, of Osaka, Japan, has been treated for nine years by Dr. Akira Yamamoto of the National Cardiovascular Center, earlier with a crude version of cholesterol filtering and more recently with a process similar to that used at Rogosin. Racked by angina at age two, she can now climb a flight of stairs without stopping. What is even more impressive to scientists is that X-ray studies show that her disease has actually regressed. "Atherosclerosis of her renal artery has completely disappeared," exults Yamamoto, and blockage around the aortic valve "is almost gone."

Reversing atherosclerosis, whether genetically or otherwise induced, has long been one of the unattainable dreams of physicians. Numerous studies have shown that the buildup of plaque in the arteries can be halted by diet, drugs and exercise aimed at controlling cholesterol levels. But a few tantalizing studies have suggested that if levels are reduced drastically enough, plaque may actually begin to melt away. Only in the past few years have doctors had the tools to achieve such reductions. LDL-pheresis is one example, while new experimental drugs like Mevinolin, particularly when combined with existing drugs, also hold great promise. "What's exciting now," observes Biochemist Thomas Parker, director of the Rogosin lipid laboratory, "is that for the first time researchers all over the world can begin to study the possibility of reversing atherosclerosis."

Many questions about the new procedure remain. Is one weekly session better than two? How long should patients be treated? The severest genetic cases, like Yuko's, would probably require lifelong treatment, says Rogosin's Dr. Bruce Gordon, but with most patients "the goal is to give a course of therapy from six months to two years, produce a beneficial effect and then hopefully keep the patient stable with diet and drugs."

Though patients undergoing LDL-pheresis have suffered few side effects, the long-term consequences are unknown. There is a theoretical risk, doctors say, that antibodies in the filter could leach out into the blood and cause allergic reactions. Many believe the inconvenience and expense of the procedure will limit its applicability. Dr. Antonio Gotto, a leading lipid researcher, estimates that a year of weekly treatments would cost $40,000. Even an LDL-pheresis enthusiast like Chazov agrees that it is not "a means of mass treatment for atherosclerosis." For that, he says, one must turn not to miraculous medical intervention, but to good, old-fashioned prevention, however boring: "We must talk about diets with lower cholesterol, exercise, control of blood pressure, and antismoking campaigns."

With reporting by James O. Jackson/Moscow and John Kohan/Bonn