Acute coronary events

Abstract

In the United States alone, more than 400,000 Americans die annually from coronary artery disease and more than 1,000,000 suffer acute coronary events, i.e., myocardial infarction and sudden cardiac death. Considering the aging of our population and increasing incidence of diabetes and obesity, the morbidity from coronary artery disease, and its associated costs, will place an increasing, substantial burden on our society. Between 2010 and 2030, total direct medical costs spent in the US for cardiovascular diseases are projected to triple from 273 to 818 billion dollars. Although effective treatments are available and considerable efforts are ongoing to identify new strategies for the prevention of coronary events, predicting such events in an individual has been challenging. In hopes of improving our ability to determine the risk of coronary events, it is prudent to review our knowledge of factors that lead to acute coronary events.

Figure 1

Histopathologic images of partially and complete coronary arterial lumen occlusion, due to thrombosis. Panel A shows an example of plaque erosion with non-occlusive thrombus in a 73-year-old man, without history of coronary artery disease, who died suddenly. The plaque shown—located in the proximal LAD—is the potential culprit lesion. The thrombus is adhering to a proteoglycan-rich intima, as demonstrated in the magnified section. Early organization of the thrombus is evident, near the intima. Panel B shows plaque erosion, with occlusive thrombus, in a 37-year-old man, who suffered an unwitnessed sudden cardiac death. The plaque shown, located in the proximal LAD, is the likely culprit lesion. Although early necrotic core (NC) is present (black arrows), there is no connection between NC and thrombus. Panel C demonstrates a ruptured plaque—with occlusive thrombus (Thr)—in a 47-year-old man with no history of coronary artery disease, who died suddenly. The plaque shown located in the proximal LAD is the likely culprit lesion. The fibrous cap is disrupted (yellow arrow), allowing the exposure of the necrotic core to the blood stream. All specimens were stained using Movat pentachrome. Abbreviations: LAD: left anterior descending coronary artery; NC: necrotic core; thr: Thrombus.

Figure 2

Histopathologic images of thin cap fibroatheromas at various stages. Panel A shows an example of an intact thin cap fibroatheroma, with large necrotic core (NC), in a 47-year-old man who died suddenly. The plaque shown — located in the proximal RCA— resulted in 70% cross-sectional lumen narrowing. Panel B shows a plaque rupture with non-occlusive thrombus (Thr), in the LCx, of a 44-year-old woman, without history of coronary artery disease, who died suddenly. The yellow arrow marks the site of the disrupted fibrous cap. Panel C demonstrates a coronary arterial cross-section, with evidence of several healed plaque ruptures, in a 55-year-old man, who died suddenly—prior to scheduled cardiac catheterization. Autopsy revealed severe three-vessel coronary artery disease. Shown is a plaque in the proximal LCx causing 80% lumen narrowing. The magnified section and black arrows highlight multiple necrotic cores (NC), which ruptured at different points in time leading to the multi-layered appearance. All specimens were stained using Movat pentachrome. Abbreviations: NC: necrotic core; RCA: right coronary artery; LCx: left circumflex coronary artery; Thr: thrombus.

Figure 3

The progression of coronary artery disease. In panel A, a cross-section of a normal artery is shown. Atherosclerotic plaque has accumulated in the next drawing (B) leading to external vascular remodeling, to minimize lumen encroachment. Panel C illustrates the event of plaque rupture and plaque hemorrhage leading to intramural thrombus. In the vast majority of cases, such plaque rupture will lead to plaque healing and growth (Panel D). In some cases, thrombus material is embolized distally, which may cause symptoms of coronary arterial insufficiency or asymptomatic microinfarctions (Panel E). In case plaque rupture coincides with a thrombosis conducive state at the site of plaque rupture or erosion, arterial thrombosis and occlusion may occur which may trigger a coronary event (Panel F).

Figure 4

The complex interplay of factors contributing to acute coronary event risk. The purpose of this illustration is to convey the complexity of factors influencing event risk, but not to provide a complete list of factors and associations involved. Both coronary thrombogenicity, i.e., a stimulus for clinically significant arterial thrombosis, and a thrombosis favorable condition need to be present for a coronary event to occur.