Playing Plumber With Our Arteries

WASHINGTON, D.C.--On the surface, it's just a simple plumbing problem. One of your pipes is clogged, and it needs to be cleaned out before flow can be restored. The only catch is that the pipe you're concerned with happens to be your coronary artery, and if you hang around until the plumber shows up, chances are you'll end up dead.

More than half a million Americans die of heart attacks every year, because the nation hasn't learned to stop clogging its arteries, and medical science hasn't found a reliable way to unclog them. But judging by the activity at the annual conference of the American Heart Association (AHA) earlier this month, medical science may be gaining some ground, and Harvard may be leading the way.

The four-day conference in Washington, D.C., brought together scientists from all over the world to discuss the latest advances in cardiovascular medicine. Included were more than 150 lectures, seminars, and poster presentations by researchers from Harvard Medical School and its affiliated hospitals. "We have a very good reputation," said Dr. Eugene Braunwald, Hersey Professor of Medicine and Physician-in-Chief at the Harvard-affiliated Beth Israel and Brigham and Women's Hospitals. "When experts are asked to rank the cardiology programs in this country, Harvard's [Massachusetts General, Beth Israel, and Brigham and Women's Hospitals] are usually 1, 2, and 3 on the list."

Braunwald's work is just one example of the fascinating new technology being developed at Harvard for the prevention and treatment of heart attack. Braunwald, along with doctors around the country, is studying the effectiveness of a new drug which acts to dissolve blood clots inside the body. Since many heart attacks are caused by a clot which blocks the coronary artery and deprives the heart of its blood supply, the drug could potentially save thousands of lives.

The substance, called tissue plasminogen activator (t-PA), is normally produced by the body in small amounts to prevent excessive clotting and to break down old clots that no longer serve any purpose. The Harvard researchers have used genetic engineering techniques to manufacture large quantities of t-PA, with the hope of bolstering the heart patient's anti-clotting mechanisms. According to Braunwald, "The aim is to use the body's own system to eliminate the clot before it can do too much damage to the heart."

But while the ability to destroy lethal blood clots may increase the chances of survival in some patients, it may have little or no effect in others. In many instances of heart attack, the coronary artery is not obstructed by a blood clot but by a fatty deposit known as a plaque. Since plaques are not susceptible to drugs like t-PA, other methods must be used to unblock the artery.

One group of Harvard researchers is experimenting with a technique which uses lasers to burn out the troublesome plaques. Although, the idea is not entirely new, it has always been plagued by the problem of how to destroy the plaque itself without damaging the normal tissue around it in the process. At the Washington conference, Martin Prince and his colleagues from Massachusetts General announced the success of a new technique.

Plaques are made up largely of fat, so they tend to absorb different colors of light than the protein-rich blood vessel tissue. By using a special laser beam that reacts especially well with the plaques and not with the surrounding tissue, the doctors have had unusual success in destroying fat deposits.

An alternative approach to unclogging the arteries is based on what scientists have learned about cholesterol. Plaques are more likely to form when blood cholesterol is high, and particularly when the cholesterol takes the form known as "low-density lipoprotein" (LDL). By lowering the levels of cholesterol in the blood or by ensuring that most of it occurs as "high density lipoprotein" (HDL), the risk of heart attack can be substantially reduced. Although, several drugs have been developed to improve blood cholesterol levels, most have been associated with severe side effects.

At the AHA meeting, Harvard researchers reported a number of successes in treating patients with high cholesterol. One group of investigators focused on niacin, a vitamin found in foods such as meat, fish, eggs, pasta, and cereals. In small amounts, the substance has long been known to be beneficial for the skin, the nerves, and the digestive system. But according to Dr. James Alderman, a senior cardiology fellow at Beth Israel Hospital, larger doses may have cardiovascular benefits as well.

Alderman and his colleagues gave patients up to two grams of niacin--more than a hundred times the recommended daily allowance of the vitamin--and found that blood cholesterol improved in 90 percent of the cases. The drug was particularly effective at raising levels of HDL (the type of cholesterol that is protective against heart disease), but it also lowered total cholesterol levels in patients taking higher doses of the drug. In general, the researchers reported, the more niacin a subject took, the greater was his improvement.

But while these results are striking, Alderman points out, they are by no means new to the medical community. Earlier research had shown that niacin could produce a marked reduction in incidence of heart attack, and an increase in survival up to 15 years after the patient had stopped taking the drug. However, use of niacin in previous studies had always been hampered by severe side effects, including headaches, flushing, itchiness, rashes, and diarrhea.

In the Beth Israel study, this problem was essentially eliminated. Only three patients had persistent side effects which required discontinuation of the therapy. In most other cases, difficulties were avoided by starting with small amounts of niacin and increasing the dosage gradually over a few weeks. Taking aspirin once or twice a day, taking the drug after meals, and using special capsules which release the niacin slowly over the course of a day were also helpful in overcoming some of the side effects. "We wanted to take away niacin's bad name," Alderman said, "and I think this study has succeeded in doing that."

The researchers are now planning a much larger experiment, comparing niacin's effects to those of other drugs and to placebos. They also plan to look at how effective niacin is at reducing the incidence of heart attacks, improving performance on stress tests, and slowing the progress of coronary pathology. While emphasizing that the results of the preliminary investigation must be confirmed by further research, Alderman made clear the potential advantages of niacin: "The most popular drug in use today produces side-effects in over 60 percent of the patients who use it, and costs over $100 a month. Niacin, on the other hand, achieves an improvement in cholesterol levels with far fewer side effects for only $5 a month per patient."

What Eskimos Eat

One of the most intriguing of the Harvard studies presented at the conference derives from research, on the eating habits of Eskimos. Studies had suggested that Greenland Eskimos have a low incidence of heart disease because they consume large quantities of seafood rich in certain oils. Based on this information, Drs. Sanford Warren and Richard Pasternak of the Beth Israel Hospital Coronary Care Unit postulated that cod liver oil could reduce the risk of heart disease.

In a study of heart patients, they found that taking eight teaspoons of cod liver oil every day for six weeks produced several changes associated with cardiovascular health. The treatment raised blood concentrations of HDL cholesterol, lowerered the rate of blood clotting, and increased production of chemicals which cause dilation of blood vessels, making arteries such as those that supply the heart less likely to get blocked up.

The researchers stress that this was only a pilot study, and that taking large quantities of cod liver oil at this stage of the game would be unwise. The oil contains vitamin A and vitamin D, which are beneficial in small amounts but can be dangerous in high doses. Also, while the substance does appear to improve cholesterol levels in the body, it actually contains a substantial amount of cholesterol itself, and this may act to reduce its overall potency.

Research is now focusing on purification of the active ingredients in cod liver oil and tests of their effectiveness on patients. The investigators are optimistic about the prospects for use of these substances, because cod liver oil seems to have no serious side effects and is substantially more palatable than most anti-cholesterol drugs currently in use.

The incidence of cardiovascular disease in this country has already begun to drop, because of improvement in dietary habits, decreases in cigarette smoking, and recent advances in surgical and drug treatments. The sophisticated methods of unblocking the coronary arteries that were announced this month in Washington will undoubtedly have an important impact on cardiovascular mortality during the next few years. But the magnitude of the problem cannot be underestimated, as heart disease continues to be the leading cause of death in the United States. As one plumber put it while writing out an itemized bill, "there's no such, thing as a simple plumbing problem." The Harvard Medical School Doctors performing heart surgery at Brigham and Women's Hospital