Inflammation at the heart of coronary artery disease

Atherosclerosis—evident in coronary artery disease—has been identified as an inflammatory disease. In the grand scheme of heart trouble, what part does inflammation play?

As the body's immediate response to an injury or infection, inflammation is an important part of the healing process. Damaged tissue sends chemical signals that trigger the flow of immune system cells to the site of injury. There they destroy bacteria, clean up dead tissue, and form a clot over the injured area to help speed repair of damaged blood vessels. The immune cells temporarily inflame the affected area but once the tissue is repaired, inflammation clears.

It's a different story, however, when inflammation doesn't settle and fade. Instead of healing tissue, chronic inflammation is key to the development of coronary artery disease and other consequences of atherosclerosis, a condition in which fatty deposits collect on artery walls. The blood vessels then become stiff and their passageway narrowed, interfering with the flow of blood. Coronary arteries are among the affected blood vessels.

How inflammation hurts the arteries

The inflammation-atherosclerosis process may play out as follows:

Step 1: The blood vessel's lining (endothelium) is damaged by unhealthy conditions such as high blood levels of cholesterol or glucose (sugar), high blood pressure, or smoking. For example, high cholesterol levels injure the artery when excess "bad" (low-density lipoprotein, or LDL) cholesterol finds its way in and becomes caught in the innermost layer of the artery, known as the intima.

Step 2: The LDL cholesterol remains in the intima as a fatty deposit (plaque). This fatty deposit sets the inflammatory response in motion.

Step 3: The immune system sends platelets (blood cells that are involved in clotting) and other specialized blood cells to the site of the plaque deposit in the intima.

Step 4: As blood cells and other substances continue to accumulate, the plaque deposit grows bigger and digs deeper into the layers of the vessel wall. More immune cells are drawn to the injured vessel, fueling the inflammation process.

Step 5: Increasing inflammation can cause the plaque deposit to break apart, or rupture.

Step 6: Blood clots form on the ruptured plaque and can block blood flow to or within the heart (causing a heart attack) or brain (causing a stroke).

The body's balancing act

Whereas some bodily processes contribute to inflammatory activity, others have an anti-inflammatory effect. This push-and-pull interaction controls the progression of atherosclerosis in each individual. For example, as illustrated above, some immune system processes provoke inflammation in the arteries. However, the immune system also produces powerful anti-inflammatory proteins and cells that protect against atherosclerosis in various ways.

Markers of inflammation

The blood contains inflammatory substances that can be measured to assess a person's risk of heart attack, stroke, and other cardiovascular problems. One such "marker" is a protein produced by the liver, C-reactive protein (CRP). CRP is released into the bloodstream when an injury or infection occurs. High levels of CRP have been linked with a heightened risk of cardiovascular disease.

CRP and other inflammatory markers such as fibrinogen and interleukins are elevated in persons who have a heart attack and those with unstable angina (heart-related chest pain that occurs with little or no exertion). However, scientists believe it's unlikely these substances actually cause heart disease. Rather, they view their presence as an indication that the inflammatory process is in progress in an artery and perhaps other tissues.

More research is needed to assess the degree to which these markers signal risk or contribute to the progression of heart disease.

Inflammation: Treatment target

Now that atherosclerosis is known to be an inflammatory disease, new opportunities for prevention and treatment of heart disease can be pursued. For example, anti-inflammatory agents or drugs that suppress the immune system may be useful therapies for certain heart problems. Experimental vaccines for the prevention of atherosclerosis have shown some success.

Those individuals who are taking statin drugs to lower their LDL cholesterol may have an advantage in the fight against inflammation: Statins have anti-inflammatory properties.

From The New England Journal of Medicine and Mayo Clinic Women's HealthSource