Kochar's Clinical Medicine for Students

CHAPTER 26 Coronary Artery Disease Columbus D. Batiste, MD Coronary artery disease is defined by the development of atherosclerosis within the coronary vasculature, which often leads to impaired coronary blood flow. Although many advances have been made in the evaluation and treatment of coronary artery disease, it remains a significant burden both economically and clinically. The lifetime risk for coronary artery disease is 49% for men and 32% for women at age 40. Despite a significant decline in mortality related to cardiovascular disease over the past 50 years, coronary artery disease continues to be the leading cause of death in the United States. The development of atherosclerosis is the primary etiology of coronary artery disease and may lead to chronic stable angina and ultimately acute coronary syndromes including unstable angina, myocardial infarction, and sudden cardiac death. It may also lead to the development of arrhythmias and congestive heart failure due to ischemic damage to the heart muscle. Atherosclerosis is the formation of plaque within the intima of large-and medium-sized blood vessels. Atherosclerotic plaque is comprised of multiple cell types including macrophages, foam cells (macrophages filled with cholesterol esters), smooth muscle cells, and lymphocytes. It also incorporates such substances as lipids, fibrous connective tissue, and minerals such as calcium. The development of atherosclerosis within the coronary arteries is a process that begins in childhood. This process is regulated by several environmental factors as well as the genetic makeup of an individual and the degree of endothelial dysfunction present. The initial atherosclerotic lesions contain atherogenic lipoproteins, which release cytokines and cause an increase in macrophages and formation of foam cells. These most frequently develop at sites of focal thickening within the intima, which are present in everyone at birth. This thickening of the intima is an adaptation to local mechanical forces and is nonobstructive. These lesions progress to fatty streaks that consist of layers of foam cells and lipid-filled smooth muscles cells. Intermediate lesions may form after puberty and are the bridge between early and more advanced atherosclerosis. These lesions contain the same layers of foam cells and smooth muscle cells as fatty streaks. At this point, smooth muscle cells can divide and elaborate extracellular matrix, leading to the deposition of extracellular matrix and scattered accumulations of lipids within the evolving plaque. These scattered areas, once dense enough, can coalesce to form an extensive but well-defined lipid core. The lesion is now considered an atheroma. Atheromas are not typically obstructive and form in the third decade of life. They often are comprised of calcium and lymphocytes in addition to lipids. The lipid core can later begin to produce collagen which then forms a tough fibrous cap, which is then termed a fibroatheroma. Extensive calcification of the lipid core can also occur. Obstruction of coronary blood flow may accompany the development of these lesions and they may develop fissures, hematomas, or even thrombus. Once disruption of the fibrous cap occurs, they are classified as complicated lesions and are often the culprit of acute coronary syndromes (Fig. 26.1). Traditional risk factors for development of atherosclerotic heart disease include smoking, diabetes mellitus, hyperlipidemia, hypertension, and family history of early coronary artery disease (males younger than 45 years, females younger than 55 years) (Table 26.1). Nearly 90% of patients with coronary artery disease have at least one of these major risk factors. More recently, additional risk factors have been taken into account including physical inactivity, obesity, dietary indiscretion, and psychosocial stress.