Coronary Artery Disease
Coronary artery disease (often referred to as heart disease) is a narrowing of the arteries that supply blood to the heart muscle. It’s caused when plaque (deposits of cholesterol, fat and other substances) builds up along the inner walls of the arteries. It can cause the arteries to become stiff and less able to expand and contract as they move blood through the body (arteriosclerosis).
Over time, plaque can accumulate and significantly impede the flow of the blood through the artery. The section of heart muscle fed by that artery won’t get enough oxygen, especially when the heart has to work harder (like during exercise). Angina (chest pain) is a symptom that an area of the heart isn’t getting enough oxygen. In severe cases, the artery can become completely blocked and the affected heart muscle will die. This is a heart attack.
In the past, researchers believed most heart attacks were caused when an artery becomes completely blocked. Today, scientists have learned that heart attacks are more likely caused when the cap over soft areas of plaque ruptures, or breaks open. The body senses this as an injury and initiates a healing response. As clots gather to seal the “break” they can clog up the artery, causing a complete blockage and heart attack.
Another consequence of plaque rupture is the potential release of plaque contents into the circulatory system. The debris can travel up to the brain, where the contents get stuck and block the narrower cerebral arteries. Here, the blockage causes a stroke (death of cells in the affected area of the brain).
The American Heart Association estimates about 17.6 million Americans have coronary artery disease. This year, about 1.4 million Americans will have a heart attack. Coronary artery disease is the leading cause of death in the U.S., killing nearly 141,500 men and women in 2006.
Risk for coronary artery disease and a heart attack increases with age. Among men, the average age at the time of a first heart attack is 64.5. For women, it’s 70.3. Some other known risk factors include: smoking, being overweight, lack of exercise, family history of coronary artery disease and having high blood pressure, high cholesterol or diabetes.
Daniel Simon, M.D., Cardiovascular Center Director at Case Western Reserve University in Cleveland, OH, says, despite the known risk factors for coronary artery disease, there is still no way to determine who will have a heart attack. Sometimes people with significant risk factors stay healthy, while others with few risk factors end up with coronary artery blockages. He says the first symptom for about 50 percent of those with coronary artery disease is a heart attack.
Simon and his colleagues began looking for clues that may predict who is at higher risk for a heart attack. With family history being associated with strong risk, they decided to look at genetic factors. The investigators compared the genes of those having a heart attack against the genes of healthy (non-heart attack) patients. One finding set the two apart – a substance called myeloid-related protein-8/14 (MRP-8/14).
MRP-8/14 appears to be responsible for clot formation and hardening of the arteries. In one study, researchers eliminated the gene responsible for production of MRP-8/14 in mice. Those mice were less likely to develop clots and hardening of the arteries.
A human study measured levels of MRP-8/14 in healthy college students and their siblings. The researchers found that the level of the protein produced by the body is genetically determined in 43 percent of those tested. In another study, investigators discovered coronary artery disease patients with high levels of MRP-8/14 were more likely to have a heart attack or die after 30 days than those with low levels of the protein.
Dealing with MRP-8/14
According to Simon, a Swiss company has already developed a rapid bedside test to measure MRP-8/14 in patients coming to the emergency room for evaluation of chest pain. The test can provide results in just 15 minutes (versus as long as eight hours for standard blood tests). In emergency rooms, the test would be an extra useful aid to medical history, EKG and standard blood markers in determining probability or risk for a heart attack. The screening test is currently being studied for use in the U.S.
A second test being considered is one that can be done in a physician’s office. Simon envisions this being used along with other standard screening tests (like cholesterol) to determine a patient’s risk for a future heart attack.
The third test is much more technical and measures the amount of MRP-8/14 in the platelets. Simon says this test may be useful for patients who already have coronary artery disease because doctors can use the results to tailor therapy.
Simon cautions that researchers are also not sure what levels of MRP-8/14 may be safe or how to reduce MRP-8/14 in patients who have high levels of the protein.
AUDIENCE INQUIRYFor general information on heart disease and stroke:
American Heart Association, http://www.heart.org
National Heart, Lung and Blood Institute, http://www.nhlbi.nih.gov
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Healy, Aileen, Ph.D., et al., “Platelet Expression Profiling and Clinical Validation of Myeloid-Related Protein-14 as a Novel Determinant of Cardiovascular Events,” Circulation, May 16, 2006, Vol. 113, No. 19, pp. 2278-2284.
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Ionita, Mihaela, et al., “High Levels of Myeloid-Related Protein 14 in Human Atherosclerotic Plaques Correlate with the Characteristics of Rupture-Prone Lesions,” Arteriosclerosis, Thrombosis and Vascular Biology, August 2009, Vol. 29, No. 8, pp. 1220-1227.
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