Coronary atherosclerosis: determinants of plaque rupture

Abstract

The most important mechanism responsible for the sudden and unpredictable onset of acute coronary syndromes is coronary plaque rupture with thrombosis and vasospasm superimposed. The risk of plaque rupture depends on plaque type (composition) rather than plaque size (volume); most ruptures occur in plaques containing a soft, lipid-rich core that is covered by a thin and inflamed cap of fibrous tissue. Compared with intact caps, the ruptured ones usually are thinner and contain less collagen (responsible for tensile strength), fewer smooth muscle cells (smc; collagen synthesizing cells), and many more macrophages (collagen degrading cells). Therefore, major determinants of plaque vulnerability and rupture are progressive lipid accumulation (core formation) and cap weakening due to ongoing inflammation with collagen degradation (macrophage-related) and impaired healing and repair (smc-related). These intrinsic plaque changes predispose plaques to rupture whereas extrinsic forces imposed on plaques, such as biomechanical and haemodynamic stresses, may determine the actual time of rupture by precipitating or 'triggering' it. Luckily, recent research in patients with coronary artery disease indicates that both plaque vulnerability and rupture triggers may be modified beneficially by treatment.