Genetic Epidemiology of Coronary Artery Disease

Coronary artery disease is responsible for almost 500,000 deaths each year making it the number one killer of women and men in the United States (1). As many as 1.5 million individuals have a myocardial infarction each year, and at least 250,000 die of their myocardial infarction within 1 hour of symptoms. Over 13 million Americans have a history of symptomatic coronary artery disease. Coronary artery disease is responsible for more than $90 billion annually in economic costs (1). Coronary atherosclerosis is the major cause of coronary artery disease (2). The atherosclerotic process is an organized, active, lifelong process involving elements of chronic inflammation followed by repair in the artery wall (3). The endothelium and many growth factors, cytokines, and vasoregulatory molecules are involved in the process (3). Atherosclerosis begins with the appearance of fatty streaks in the intima (4). The fatty streaks may evolve into fibrous plaques by accumulation of lipid, smooth muscle, and connective tissue. These plaques undergo vascularization, intraplaque hemorrhage, rupture, ulceration, and calcification and can impede blood flow through an artery. A thrombosis superimposed on a lesion can lead to myocardial infarction or sudden death (4). Comprehensive studies to date have identified risk factors for coronary artery disease endpoints including sudden death, myocardial infarction, or angina pectoris (see table 1). These established risk factors include older age, male sex, elevated total cholesterol levels, elevated low-density lipoprotein cholesterol levels, reduced high-density lipoprotein cholesterol levels, hypertension, diabetes mellitus, smoking, obesity, physical inactivity, and family history of premature coronary artery disease (5, 6) (see table 1). These factors, however, fail to identify a large proportion of