Pathophysiology and inflammatory aspects of plaque rupture

Atherosclerotic plaque disruption with superimposed thrombosis is the main cause of acute coronary events. At present it is not known specifically how various risk factors influence the development and configuration of coronary plaques. The risk of plaque disruption depends more on plaque composition and vulnerability (plaque type) than on the degree of stenosis (plaque size). Lipid accumulation and chronic inflammation, particularly macrophage activities, seem to influence the development and the stability of a plaque and thus its propensity to rupture. Macrophages have the ability to secrete proteolytic enzymes and often infiltrate the region of imminent plaque rupture, and disruption may be associated with a generalized inflammatory reaction. Further, plaque disruption tends to occur at points where the plaque surface is weakest, corresponding to locations where mechanical and hemodynamic forces have their highest impact. The risk of plaque disruption is a function of both plaque vulnerability (intrinsic disease) and rupture triggers (extrinsic forces). The former predisposes the plaque to rupture; the latter may precipitate rupture. The danger of vulnerable plaques, however, is not related to disruption as such but to the resulting thrombosis. The magnitude of this thrombotic response and the ensuing flow obstruction depends on the contents and quantity of exposed thrombogenic plaque material, the degree of pre-existing stenosis, and the systemic thrombotic tendency. The thrombotic response is a dynamic process that is decisive for the clinical presentation and the outcome.