Therapeutic approaches to the control of coronary atherosclerosis.

Abstract

Atherosclerosis is a multifactorial disease which culminates in the ruptured plaque seen at autopsy. Hypercholesterolaemia, subintimal accumulation of lipid, monocyte adhesion followed by penetration across the endothelium, the conversion of monocytes to macrophages and smooth muscle cell proliferation and migration are some of the events involved in the early stages of lesion formation. Late events include the formation of excess ground substance and collagen, and the formation of the fibrotic cap. Young lesions tend to be more fragile than "old" calcified lesions, and it is these young lesions which rupture, haemorrhage and provide anchor points for platelets. Therapeutic interventions aimed at controlling lesion formation include those which reduce risk factors, including hypertension as well as those which interfere with the cascade of events involved in lesion formation. Agents which lower plasma cholesterol provide one approach. Another approach is to use calcium antagonists which not only lower blood pressure, but also directly interfere with some of the metabolic events involved in lesion formation.