PLAQUE REGRESSION, PLAQUE DISRUPTION AND CLINICAL EVENTS - A RATIONALE FOR LIPID-LOWERING IN CORONARY-ARTERY DISEASE

Lipid lowering therapy appears to benefit the arterial disease process , as assessed by angiography. For example, in the Familial Atheroscler osis Treatment Study (FATS), the frequency of progression, per lesion at risk, was reduced by 75% among mild and moderate lesions, which for m the great majority of the lesion population. Regression frequency, p er lesion, is more than doubled in mild and moderate subgroups and qua drupled in the severe lesion subgroup. Clinical events were reduced by 73% in FATS; this was entirely due to a reduction in the likelihood t hat a mildly or moderately-diseased arterial segment would undergo abr upt and substantial progression to a severe lesion precipitating the c linical event. The occurrence of plaque fissuring, leading to plaque d isruption, thrombosis and clinical coronary events, is predicted by th e presence of a large fraction of core lipid in the plaque and a high density of lipid-laden macrophages in the fibrous cap of the atheroma, and possibly by cytotoxic concentrations of oxidized low density lipo protein (LDL) products. Lipid-laden macrophages can be largely elimina ted and core lipid in the plaque can be reabsorbed when lipid levels a re 'normalized' in experimental animals. Data suggest that these mecha nisms also operate in certain lesions in man, supporting the hypothesi s that lipid-lowering therapy selectively depletes (regresses) those f atty lesions containing a large lipid core and dense clusters of intim al macrophages. Such lesions, most vulnerable to fissuring, thereby be come more stable and the clinical event rate is accordingly decreased.