Atherothrombosis is a systemic arterial disease of large- and medium-sized arteries including the coronary, carotid, aorta, and peripheral arteries. The clinical manifestations depend on the size of the vessels and the regional circulation involved and include coronary artery disease, stroke, and peripheral vascular disease. A paradigm shift is occurring with a change in focus from the assessment and treatment of luminal narrowing toward greater understanding of the vascular biology in the arterial wall that leads to plaque vulnerability. Recent research has shown that inflammation plays a key role in the pathogenesis and progression of atherothrombosis. The basic concepts of evolution of atherothrombosis, and the role of inflammation leading to vulnerable plaque, will be discussed here.
The main components of atherothrombotic plaques are1,2,3,4,5,6,7 (1) connective tissue extracellular matrix, including collagen, proteoglycans, and fibronectin elastic fibers; (2) crystalline cholesterol, cholesteryl esters, and phospholipids; (3) cellular components such as macrophages, T lymphocytes, and smooth muscle cells; and (4) thrombotic material with platelets and fibrin deposition. The proportion of these components varies in different plaques, and explains the heterogeneity of lesions and potential vulnerability to plaque rupture.
CLASSIFICATION OF ATHEROTHROMBOTIC LESIONS
According to a simplified modification of the criteria set forth by the American Heart Association Committee on Vascular Lesions,3 plaque progression can be classified into five phases as shown in Figure 4-1.
Phase 1: (early): These lesions are small and commonly seen in individuals younger than 30 years. Based on their composition, these plaques are categorized into three types: type I lesions, consisting of macrophage-derived foam cells with intracellular lipid droplets; type II lesions, consisting of macrophages, smooth muscle cells, and extracellular lipid deposits; and type III lesions, consisting of smooth muscle cells surrounded by extracellular connective tissue, fibrils, and lipid deposits. It is possible for these early lesions to regress to normal.8
Phase 2: (advanced): These lesions, although not necessarily stenotic, may be prone to disruption because of their high lipid content, thin fibrous caps, and increased inflammation. They are categorized into two types: type IV lesions, which consist of confluent cellular lesions with a great deal of extracellular lipid intermixed with fibrous tissue, and type Va lesions, which possess an extracellular lipid core covered by a thin fibrous cap. Phase 2 plaques can evolve into the acute phases 3 and 4, and either of these can evolve into phase 5 plaques.
Phase 3: This phase consists of acute complicated type VI lesions, originating from disrupted type IV or Va lesions, and leading to mural, nonobstructive thrombosis. Although clinically silent, the process may occasionally lead to the onset of angina.9
Phase 4: This phase includes acute complicated type VI lesions, with fixed or repetitive occlusive thrombosis. This process may be ...
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