THE EFFECT OF PRAVASTATIN IN RELATION TO LOW-DENSITY-LIPOPROTEIN RECEPTOR ACTIVITY

Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, suppresses new synthesis of cholesterol via HMG-CoA in hepatocytes. As a result. low density lipoprotein (LDL) receptor activity in the liver is enhanced, which leads to lowering of plasma cholesterol. Inhibitors are shown to be effective in heterozygous familial hypercholesterolaemia (FH). Although FH heterozygotes are defined genetically as possessing half the normal LDL receptor activity, some heterogeneity of LDL receptor activity is observed in these patients. To see whether the effect of an inhibitor is related to LDL receptor activity in each patient, pravastatin was administered to 7 FH heterozygotes for 3 months at a daily dose of 10 mg; their mean LDL receptor activities measured before the therapy were 4.5.0±9.9% of the normal control. After medication, mean serum total cholesterol decreased from 349.0 to 279.7 mg/dl (p<0.05), and LDL-cholesterol decreased from 272.6 to 207.7 mg/dl (p<0.05). A significant correlation between the initial LDL receptor activity and the effect of pravastatin was not proved. However, the pre-treatment level of LDL-cholesterol was positively correlated (r=0.79.5) with the absolute decrement of LDL-cholesterol after 3 months (p<0.0.5). This implies that the more LDL-cholesterol was elevated, the more pravastatin was effective. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.