Doctors are beginning to talk about a new way of preventing heart attacks and strokes that can be used along with agents like aspirin that partially block blood clotting. The new strategy is called stabilization of the vulnerable plaque. A vulnerable plaque is one that is close to the point of rupturing. Our knowledge is improving on how vulnerable plaques can be stabilized and ruptures prevented, even in people who have widespread and severe atherosclerosis. The most important method appears to be lipid control - that is, reducing LDL and probably increasing HDL. One should remember that cholesterol, the major chemical found in the plaque core, can actually be removed from therosclerotic tissue by HDL. There is a race between LDL carrying cholesterol into the atherosclerotic core and HDL removing cholesterol from the core. The outcome depends upon the balance of these two processes.
An exciting research study recently reported from Seattle suggested that it might be possible to remove most of the cholesterol from atherosclerotic plaques by intensive lipid management. The research group at the University of Washington in Seattle had maintained 60 patients with coronary heart disease for 10 years on good diets as well as drugs that lower LDL and raise HDL levels in blood (the drugs were simvastatin [Zocor], niacin, and colestipol [Colestid] used in combination). Eight of these patients were randomly selected to have a new magnetic resonance imaging (MRI) procedure performed. The new MRI technique allowed the researchers to "see" the lipid and fibrous components of atherosclerosis in the carotid arteries, almost as if they were pathologists looking through a microscope. In cross-section views of the arteries, eight matched control patients (who had not received lipid treatment) showed a lipid core occupying 17% of the area. In the 8 intensively treated patients, the lipid core averaged only 1% of the area. Thus it appears that the lipid core of the atherosclerotic plaques, presumably similar to that in the control patients 10 years ago, may have been almost entirely removed by the intensive lipid treatment.
Heart catheterizations are very often performed with the intention of determining how many blockages exist in the coronary arteries and how severe the blockages are. Almost all such blockages are due to atherosclerotic plaques that narrow the channel for blood flow in the arteries. Very severe blockages (ones that narrow the channel by 70% or more) can be treated by balloon catheters that expand the channel, or by balloon catheters followed by wire mesh "stents" that keep the channel expanded, or by bypass surgery that inserts new blood vessels to re-establish good blood flow downstream of the blocked places. All of these heart catheterization procedures and bypass surgeries would not be needed if it were possible to shrink the atherosclerotic plaques by using - for example - cholesterol drugs. Can this be done by using diet and drugs instead of catheters and surgeries? Unfortunately, the answer is usually no. Some patients with blocked coronary arteries causing cardiac chest pain (called "angina") can improve with diet and drugs, but usually they do not improve very much. The very best diet and drug regimens might improve coronary artery blockage by, on average, 1% to 2% (we'll discuss this later). This is not a very meaningful percentage improvement when the blockages causing anginal chest pain are 70% to 99% blockages.
As research studies were performed to measure the effect of diet and cholesterol drugs on coronary artery blockages, a startling and important discovery was made. Although, as stated above, the degree of blockage changed very little, the number of heart attacks and heart-related deaths in the patients dropped dramatically. In a few studies, the number of heart attacks, heart related deaths, and episodes of rapidly worsening chest pain dropped by 70% to 80%. In many studies, these "cardiac events" dropped by 20% to 40%. These results were far out of proportion to the tiny 1% to 2% improvements in the heart blockages. What was going on?
The answer seems to be as follows: Diet and cholesterol drugs do not change the overall size of atherosclerotic plaques very much at all, so that the blockages improve very little. However, diet and cholesterol drugs have some kind of effect on plaques to make them much less prone to rupture. As stated at the beginning of this section, the "vulnerable plaques are stabilized."
Experiments in animals have helped us to understand what happens when vulnerable, ruptureprone plaques are stabilized. You may recall that macrophages in the fibrous cap of atherosclerotic plaques play an important role in plaque rupture. Macrophages make enzymes that break down the fibrous proteins of the arterial wall. These macrophages also form many large foam cells that can almost totally occupy parts of the fibrous cap. In animal experiments, when LDL levels in the blood are lowered and/or when HDL levels are raised, the foam cells lose their cholesterol, and eventually the foam cells and most of the macrophages disappear from the atherosclerotic plaque. What is left behind is strong fibrous tissue that is not prone to rupture. This improvement in the atherosclerotic plaque can be accomplished within one to three months in animal experiments. It is thought that the same things happen in human atherosclerotic plaques, when LDL is lowered, HDL is raised, or both. It is possible to stabilize the vulnerable plaque, even when the overall size of the plaque changes very little. Certainly this is good news, since almost all heart attacks, most strokes, and most cardiovascular deaths appear to happen when vulnerable plaques rupture.
The take-home message is this: When a person is experiencing severe anginal chest pain due to coronary artery blockages, that person usually needs a heart catheterization. A balloon procedure to stretch open a blocked artery may then be performed, often with placement of one or more stents, or alternatively, coronary bypass surgery may be performed. These procedures in the catheterization laboratory or in the operating room do a good job of relieving anginal chest pain. However, these procedures usually don't reduce the risk of subsequent heart attacks, strokes, and heart-related or vascular deaths very much. That is a job for diet, lifestyle, and drug treatment, which can drop the risk of sudden atherosclerotic events by half or more. Treatment of atherosclerosis with diet, lifestyle, and drugs changes the risk factors such as LDL, HDL, blood pressure, and smoking. In addition, drugs that partially block blood clotting, such as aspirin, can help to prevent heart attacks, strokes, and cardiovascular deaths. So, getting your arteries opened up with balloons and stents, or getting your arteries bypassed surgically does not prevent heart attacks, strokes, and deaths very well. A great deal more can be done to prevent these events by improving risk factors and by partially blocking blood clotting.
John R. Guyton, MD