Doctors Offer Explanation of Heart Attacks
A pair of UC Irvine physicians are challenging the conventional wisdom on why people have heart attacks, linking the attacks to a destructive inflammation process rather than simple plaque buildup in the arteries.
The preliminary findings suggest that heart attacks are less an inevitable product of an unhealthy lifestyle than the mysterious work of plaque-degrading enzymes, says UCI pathologist Benjamin Victor, who presented the work Tuesday at an American Heart Assn. conference in New Orleans.
“In and of itself this first step doesn’t do anybody any good, but if they can find a way to block these enzymes, they could potentially prevent [most heart attacks] . . . the leading cause of death in the Western world,” Victor said this week.
Victor and his research partner, cardiologist Richard Helfant, built on a steady foundation of earlier research suggesting that inflammation plays a role in heart attacks.
Their own previous study suggested that people who died of heart attacks had clusters of inflammatory cells in their plaque, while those who died of other causes might have had plaque but did not have the inflammatory cells.
That led them to wonder whether the cells, called macrophages, were in the plaque before the heart attack or came in later as part of a repair operation. This was their essential question: Was the inflammation a cause or an effect of the heart attack?
Working with the Orange County coroner’s office, Victor had a research edge: ready access to the bodies of sudden heart attack victims. He and Helfant discovered that, in these people, the macrophages seem to be present all along, whether they die immediately or live a few days. The patients who lived longer did not have a greater proportion of macrophages, or a different density or type, suggesting that these cells were a cause of the heart attack, not a reaction to it.
The researchers postulate that, in patients vulnerable to heart attacks, the macrophages release a variety of enzymes that dissolve the collagen, or binding protein, that caps plaque and keeps it stable in the artery. When the plaque tears open, a blood clot forms at the place of injury, further blocking the already narrowed vessel. Ultimately, blood flow to the heart is interrupted, causing a heart attack.
“Most people think heart attacks are caused by the continuous narrowing of the arteries,” Victor said. “But it’s not like that. Some people don’t have much plaque--but their plaque is tearing open and causing heart attacks.”
Patients without the inflammatory cells probably won’t suffer a heart attack, Victor said, but they are vulnerable to shortness of breath and a progressive weakening of the heart that can be fatal.
The American Heart Assn. warned Tuesday that the research is not a reason to abandon healthy lifestyle habits such as low-fat diets or exercise. Much remains unknown about this inflammation process--including what causes it in the first place. And the study sample of the UCI researchers was small: four heart attack victims who died suddenly and six who died after a few days.
The UCI research is not ground-breaking, said Dr. Gregg Fonarow of UCLA Medical Center’s division of cardiology, but it does bolster existing suspicions that respiratory infections and low-grade chronic inflammation may create “vulnerable regions” in the coronary arteries that ultimately cause heart attacks.
“The inflammatory response seems to explain almost all heart attacks,” he said.
Other researchers say inflammation studies are a promising line of inquiry with important clinical implications.
“It’s a hot area,” said Dr. Bruce H. Brundage, chief of cardiology at Harbor/UCLA Medical Center in Torrance, who is attending the New Orleans conference. “In terms of relevance, it’s right on the cutting edge, thinking that inflammation may weaken the plaque and set off a series of events leading to a heart attack.”
Atherosclerosis, the buildup of plaque in the arteries, has proved much more complex than anyone anticipated, Brundage said.
“We’re just mainly dealing with the tip of the iceberg,” he said. “[But] we’ve come a long way since the early days when a lot of scientists thought [atherosclerosis] was just deposits of fat in the walls of an artery.”
(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)
A Second Opinion
Heart attacks may be caused not by a continuous narrowing of the coronary arteries but by anout-of-control inflammatory reaction. Here’s what happens:
1. Plaque deposits (cholesterol and other fats) form on coronary artery inner lining. Collagen, a tough fibrous protein, keeps the plaque deposits stable. Although artery is narrowed, blood still flows, supplying the heart muscle.
2. Macrophages, inflammatory cells living in the fibrous cap, produce enzymes. Enzymes dissolve collagen. When plaque reservoir tears, blood clot forms, closing the already narrow vessel and causing heart attack.
Cross sections of coronary arteries
Vessel wall
Vessel opening
Collagen cap
Plaque pool
Macrophages
Torn ends of collagen cap
Blood clot
Source: Dr. Benjamin Victor
