Cholesterol lowering and the vessel wall: New insights and future perspectives

The basis for most acute coronary events is either rupture or fissuring of unstable atherosclerotic plaques with subsequent thrombosis leading to coro nary artery occlusion. The development of atherosclerotic plaques takes sev eral decades, but the mechanical features determining its stability and the risk of rupture can change very rapidly depending on a number of internal factors. Unstable plaques have a large lipid core, a thin overlying fibrous cap and an abundance of inflammatory cells. The most important factor dete rmining the plaque stability is the plasma level of atherogenic LDL particl es. Increased levels of these particles cause endothelial dysfunction with impaired vasodilatation capacity and prevalence of vasoconstriction, mainta in inflammatory infiltration of the plaque, impair the strength of the fibr ous cap and facilitate aggregation and coagulation. Effective lowering of p lasma cholesterol by pharmacological and non-pharmacological means can reve rt most of these processes and increase the plaque's mechanical stability w ithin several hours to days. Lipid lowering therapy can therefore decrease the risk of acute coronary events within a very short space of time. Thus a radical decrease in lipid levels, along with modification of other risk fa ctors, may become the cornerstone for treatment of acute coronary syndromes , in addition to being an effective treatment in primary and secondary prev ention of coronary heart disease (CHD).