By Sean Henahan, Access Excellence

NEW ORLEANS (Nov 12, 1996) Heart attacks might be triggered by misguided elements of the inflammatory response, according to new studies presented at the American Heart Association's 69th Scientific Sessions.

"The leading cause of death in the western world is heart attack," said Dr. Benjamin C. Victor, M.D., Ph.D., chief resident in pathology at the University of California, Irvine Medical Center. "It used to be considered an inevitable product of our lifestyle, but perhaps it's just an inflammatory process out of control."

Victor studied macrophages, a class of white blood cells that abound when inflammation is present within the body. Macrophages also are present in plaque, the deposits of cholesterol and other fatty substances that narrow the arteries in atherosclerosis and contribute to heart attack.

Inflammation is the body's reaction to injury. "Every time your body is doing anything to repair itself, there's going to be remodeling. Macrophages are part of the dissolving and rebuilding process," Victor said.

Victor studied macrophages that produce enzymes that break down collagen, the tough, connective-tissue protein found throughout the body. Collagen forms a thick cap that keeps atherosclerotic plaque stable. Stable plaque narrows the vessels but does not cause heart attacks, he said. However, when the plaque tears open, a blood clot forms at the point of injury. The blood clot can block the already-narrowed vessel, cutting off blood flow to the heart and causing a heart attack. And, the amount of damage to heart muscle is directly proportional to the amount of time blood flow is absent.

"Most people think heart attacks are caused by the continuous narrowing of the arteries (with plaque)," he said. "But it's not like that. Some people don't have much plaque but their plaque is tearing open and causing heart attacks."

In a previous study, Victor and co-researcher Richard H. Helfant, M.D., of the UC Irvine's division of cardiology, had shown that people who died from heart attacks had clusters of collagen-dissolving inflammatory cells in their plaque, whereas people who died of other causes may have had extensive plaque but without those inflammatory cells, he said.

"The people having heart attacks have vessels that are loaded with these macrophages that are producing these enzymes. The others have stable plaque," Victor said.

Previous studies were unable to determine whether the inflammatory cells were in the plaque before the heart attacks occurred -- perhaps even causing them -- or gravitated to the point of injury after the attack, he said.

"The big question is whether the cells making these enzymes are there because there was a rupture or are there before the rupture happens" he said.

Victor and Helfant studied ruptured plaques from 10 people whose cause of death was heart attack -- four who died within an hour of having a heart attack and six who died several days after their heart attacks.

Using a recently developed probe, they studied macrophages that produce three collagen-dissolving enzymes, known as matrix metalloproteinases (MMPs) 1, 2 and 3.

"We found no significant difference in the amount of inflammatory cells in the two groups. So we think they are present at the time of the heart attack," Victor said.

If the researchers had found more inflammatory cells in the patients who survived longer that would have indicated that those cells were moving in to repair the damaged vessels, he explained.

"It looks like these inflammatory cells are actually causing the plaque to break open and cause the heart attack, rather than being an inflammatory response after the heart attack," he said.

This research could lead to a change in the way scientists view heart attacks, he said. "Maybe it's not an inevitable product of our lifestyle. It could be just another inflammatory disease, such as arthritis. The clinical relevance would be if there were some way to inhibit these enzymes you might be able to prevent heart attacks," he said.