The pathophysiology of acute coronary syndromes

Virtually all regional acute myocardial infarcts are caused by thrombosis developing on a culprit coronary atherosclerotic plaque. The very rare exceptions to this are spontaneous coronary artery dissection, coronary arteritis, coronary emboli, coronary spasm, and compression by myocardial bridges. Thrombosis is also the major initiating factor in unstable angina, particularly when rest pain is recent and increasing in severity. Necropsy studies suggest that a new thrombotic coronary event underlies 50–70% of sudden deaths caused by ischaemic heart disease. Given the importance of thrombosis as the trigger for acute myocardial ischaemia, it is necessary to know something about the structure of plaques before thrombotic events occur and why there should be a sudden change from a stable state (no thrombus) to an unstable state (thrombus). The fully developed human fibrolipid plaque, designated by the American Heart Association (AHA) as type IV or type Va,1 has a core of lipid surrounded by a capsule of connective tissue (fig 1). The core is an extracellular mass of lipid containing cholesterol and its esters, some of which is in a crystalline form. The core is surrounded by numerous macrophages, many of which contain abundant intracytoplasmic droplets of cholesterol (foam cells). These macrophages are derived from monocytes which crossed the endothelium from the arterial lumen. They are not inert or end stage cells, but are highly activated, producing procoagulant tissue factor and a host of inflammatory cell mediators such as tumour necrosis factor α (TNF α), interleukins, and metalloproteinases. The connective tissue capsule which surrounds this inflammatory mass is predominantly collagen synthesised by smooth muscle cells. The portion of the capsule separating the core from the arterial lumen itself is the plaque cap. Figure 1 The established stable plaque. In this cross section of a human coronary artery there is an established fibrolipid plaque with a …