Coronary artery disease, commonly referred to as coronary heart disease, atherosclerosis or ischaemic heart disease, is the result of plaques that form in the major arteries supplying blood to the heart. According to the report published by the American Heart Association for 2007, Heart Association Statistics Committee and Stroke Statistics Subcommittee on Heart Disease and Stroke Statistics—2007 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Committee, an estimated 1 in 3 American adults have one or more types of cardiovascular disease, and coronary heart disease caused 1 of every 5 deaths in the U.S. in 2004. Additional data from the Agency for Healthcare Research and Quality (AHRQ) show that 11.6% (12.9 million) of women and 11.4% (11.7 million) of men age 18 and older reported being told by a doctor that they have cardiovascular disease (CVD). In every year since 1900 except 1918 (the great influenza epidemic), CVD accounted for more deaths than any other single cause or group of causes of death in the United States. This year, an estimated 700,000 Americans will have a new heart attack and about 500,000 will have a recurrent attack.
A study of men and women in three prospective cohort studies found about 90% of the coronary heart disease patients have prior exposure to at least one of these major risk factors, which include high total blood cholesterol levels or current medication with cholesterol-lowering drugs, hypertension or current medication with BP-lowering drugs, current cigarette use, and clinical report of diabetes.
The estimated direct and indirect cost of cardiovascular disease for 2007 is $431.8 billion, according to the AHA report.
The arterial blood vessels, or those major vessels that carry blood to all organs, carry lipoproteins through the body. In coronary artery disease, the plaques are deposited in the walls of the arteries. These plaques cause a chronic inflammatory response known as atherosclerosis. Every one of us, from the moment of birth, begins to accumulate these plaques. But it is the inflammatory response to the plaques that cause complications that are chronic, slowly progressing and cumulative.
The soft or vulnerable plaque can suddenly rupture causing the formation of a blood clot that will rapidly slow or stop blood flow often within five minutes, leading to death of the tissues fed by the artery. This catastrophic event is called an infarction. One of the most commonly recognized scenarios is called coronary thrombosis of a coronary artery, causing myocardial infarction (a heart attack).
Dr. Klaus Ley studies the underlying factors that contribute to the disease atherosclerosis, and more specifically the chronic inflammatory response. His research has uncovered the role of leukocytes (cells of the immune system), and specifically the role of adhesion molecules, in the formation of these arterial plaques. Selectins are cell adhesion molecules that line the interior surface of blood vessels and are stimulated and expressed as part of the immune response. In other words, during inflammation, selectins play an important part in recruiting leukocytes to the site of injury. Specifically, P-selectin and E-selectin recruit the body’s immune cells to the site of inflammation (where the plaque accumulates) and causes them to “roll” along rather than bind to the plaque. Additional molecules called inflammatory chemokines are responsible for activating the clotting mechanism in the immune response. Dr. Ley is studying this interaction of proteins and molecules and how unstable plaque can be made more stable. More specifically, Dr. Ley is working on preventing certain proteins from binding to the site after the plaque ruptures, creating an infarction that results in death. The disease atherosclerosis is chronic, but the event is acute. Reduce occurrence of the event, reduce the death rate.
“Forty percent of heart attacks kill you before you reach a hospital, and you never even knew you had anything wrong,” said Ley.
Other complications resulting from atherosclerosis include abdominal aortic aneurysm (known as AAA), a weakness in the abdominal aorta that causes dilation or a bulging out in a portion of the artery. If the bulge ruptures, you can die. This aneurysm affects mostly the elderly, the majority of whom never even know they have the disease. At age 65, Medicare will pay for an expensive test specifically to detect this problem, but if you don’t get the test when you are 65, Medicare will never pay for it again. If a cheaper blood test could be created to enable everyone over 60 to get the test as-needed, those with an abdominal aortic aneurysm could get help before the vessel ruptures. Out of hundreds of biomarkers for the disease that causes this abdominal aortic aneurysm, or bulge, Dr. Ley has identified four candidate biomarkers for the disease. Dr. Ley’s research is essential to the ultimate creation of a test for AAA that is as good as or better than PSA (prostate-specific antigen) is for prostate cancer. This would save lives by making diagnosis more available and affordable.
“Even if you make a five percent dent in a disease, you're talking about tens or hundreds of thousands of people,” said Ley. “I do very basic work. At the end of the day, it's nice to have something that ties back to helping real people.”
