Genesis of Fatal Heart Attacks Lurks in Artery Walls
For a long time, the cause of heart attacks seemed so simple, so obvious: Big, nasty clumps of gunk build up on the walls of the heart’s arteries. The blood channel grows tortuously narrow. Eventually a clot gets stuck, choking off the flow entirely. Heart muscle starves and dies.
Simple? Yes. Accurate? No.
Medicine’s understanding of what causes heart attacks is undergoing a rewrite.
Contrary to common sense and pleasingly straightforward textbook explanations, it now appears that these large blobs are not the ones to worry so much about. They do cause problems, but they are probably to blame for no more than 15% or so of all heart attacks.
Instead, it’s the far more numerous small ones that matter most, and these are largely ignored by cardiologists because they cannot even see them.
The new thinking boils down to a single phrase, one that almost certainly will enter the lexicon of everybody-knows-that health dogma in the years to come. It’s this: vulnerable plaque.
Plaque is the stuff of hardening of the arteries, what doctors call atherosclerosis. It’s something like rust inside a pipe. Some plaque is hard and solid; some is soft and squishy.
It’s the soft variety that experts say we should worry about. They call it vulnerable because of its unhappy tendency to burst.
Plaque breaking inside the heart’s arteries is the single most common lethal event of the industrialized world. The rupture launches a chemical chain reaction that often culminates with a big blood clot. When the worst happens, this clot blocks one of three main arteries crawling along the surface of the heart that supply blood to the heart muscle itself.
“The rupture of a plaque will be the cause of death of about half of all of us in the United States,” says Dr. Steven Nissen of the Cleveland Clinic. “Understanding why they rupture is probably the most important question today in cardiology and even the most important question in all the country.”
This is basic biology with a clear practical payoff. Understanding vulnerable plaque opens new strategies for finding people who are at risk of heart attacks so treatments can be targeted to prevent them.
Already this quiet breakthrough is helping to answer several conundrums of heart disease. Among them:
Why do heart attacks so often strike people at the seeming peak of health, with no warning?
Why do the mainstays of treating atherosclerosis--everyday bypass surgery and angioplasty--fail to prevent heart attacks and death?
Why do the new cholesterol-lowering statin drugs do such a good job of reducing these risks without improving the heart’s blood flow?
In the old days--say, five years ago--it was generally thought that the worst kind of plaque was the stuff that causes pain or tightness in the chest, called angina.
One reason the significance of small but vulnerable plaque has been slow to dawn is that cardiologists have not worried much about the things they cannot see. And what they see is limited largely to the power of the angiogram.
For this test, done 1.1 million times a year in the United States, doctors inject opaque dye into the heart arteries, then aim an X-ray camera. It produces black-and-white movies of the channel running through the arteries.
Doctors look for spots where thick rims of plaque slow blood flow to a trickle. In these places, the heart gets too little oxygen, and even modest exertion can cause chest pain. The next step is eliminating the big obstructions--and the pain--by rerouting blood flow with bypass surgery or squeezing open the channel with angioplasty balloons.
But tending to these blockages does nothing much to prevent heart attacks. The reason, it turns out, is that the angiogram shows only the plaque that causes pain, not the plaque that’s likely to break.
“Trying to understand plaque by looking at an angiogram is like trying to understand a doughnut by looking at the hole,” says Dr. Peter Libby of Brigham & Women’s Hospital in Boston.
Libby and others are studying the doughnut: the walls of the artery. And they are discovering that plaque, like most things in the body, is a complicated structure. The rusty-pipe analogy hardly begins to describe it.
Here’s one of the most important things to know about plaque: It usually doesn’t bulge inward. Instead, as plaque grows, it often protrudes outward into the wall of the artery, rather than into the channel where blood flows.
On an angiogram, everything looks normal. But when dissected after death, the arteries’ walls are thick with plaque that cannot be seen otherwise.
“By the time you see an irregularity on the angiogram, the first little 25% narrowing, over 85% of the rest of the arteries are atherosclerotic,” says Nissen. “It’s all hidden.”
This is why the first sign of heart trouble is so often a heart attack. A vulnerable bit of plaque bursts long before any of it gets big enough to protrude into the channel and cause angina. So the victim looks, feels and acts perfectly healthy until the moment he drops dead.
“Not all plaques are alike,” says Dr. Frank Kolodgie of the Armed Forces Institute of Pathology in Washington, D.C. “Some are harmful and some are benign. What distinguishes the two is mostly determined by the physical makeup of the plaque.”
Harmful or benign, cholesterol is a key part of the makeup. In fact, there are two forms--cholesteryl ester, which is soft, and crystalline cholesterol, which is hard. But added to this are many other ingredients, including smooth muscle cells, white blood cells, calcium and fiber that forms a cap over the whole thing, protecting it from contact with the blood flow.
Plaques are thought to begin as a response to injury to the artery wall. This damage might result from many things, including high blood pressure, smoking or high cholesterol. Whatever the cause, one response to the injury over time may be a buildup of soft cholesterol.
The body seems to confuse this cholesterol with an infection, so it sends in germ-fighting blood cells. This inflames the plaque and has several unfortunate consequences. Among other things, the white cells produce tissue factor, which generates a big clot if it comes in contact with blood, and metalloproteinases, enzymes that eat away at the fibrous cap.
“There is a contest going on between factors that favor reinforcement of the plaque with the fibrous skeleton that gives it strength against rupture, and the process that weakens it,” says Libby. “In any given plaque, there’s a time in history when the dark side will win.”
When the dark side wins, the plaque contains large amounts of soft cholesterol, has many white blood cells and is topped with a thin fibrous cap. At this point, almost anything can break it--even climbing out of bed in the morning.
The hormonal surge needed to face the day can break vulnerable plaque and helps account for the peak in heart attacks around 9 a.m. Shoveling snow, arguing, sex and other stresses can do the same thing, but they aren’t necessary.
“Mechanical forces can easily disrupt this plaque, just the vibration of the heart as it beats,” says Dr. Valentin Fuster of Mt. Sinai School of Medicine in New York City and president of the American Heart Assn.
Although a rupturing plaque can lead to a heart attack, most of the time nothing much bad happens. In fact, it appears that plaques break all the time, and those that trigger heart attacks are the unlucky exception. Doctors think that the large plaques visible on angiograms are often the healed-over and more stable remains of small vulnerable plaques.
Finding ways to make vulnerable plaques more stable is an obvious goal of this research. In a kind of medical serendipity, it appears that doctors have recently acquired medicines that may do just this.
A new class of cholesterol-lowering medicines called statins, which includes such drugs as Pravachol and Mevacor, have already proven to be a true breakthrough in heart protection. For people at high risk, the drugs can cut the chance of heart attack and death by more than half. Even outwardly healthy people with normal cholesterol levels may reduce their risk by 20% or so.
Despite the huge effect on heart disease, doctors have been puzzled to find that the drugs reduce the degree of narrowing seen on angiograms by a mere 2% or less.
Now they theorize that statins do their work, at least in part, by drawing the soft cholesterol out of plaque, leaving it firmer, more stable and less inflamed--but not necessarily much smaller.
“In this part of life, as in others,” says Libby, “size isn’t everything.”
