Pravastatin therapy in primary moderate hypercholesterolaemia: changes in metabolism of apolipoprotein B-containing...

This study examined the actions of pravastatin on the metabolism of apolipoprotein B (apo B) in very low-, intermediate-, and low-density lipoproteins (VLDL, IDL, and LDL) in 10 patients with primary moderate hypercholesterolaemia. 131I-VLDL apo B was used as a tracer, and appearance of label was followed into IDL apo B and LDL apo B. Compared to placebo, pravastatin therapy reduced levels of cholesterol in total plasma. LDL, VLDL, and IDL cholesterol by 25%, 29%, 31%, and 47%, respectively. Pravastatin treatment also significantly decreased concentrations of apo B in LDL, IDL, and VLDL. The drug significantly reduced the mean production rate for VLDL apo B by 40%, and decreased production rates for LDL apo B in eight of 10 patients. In contrast, fractional catabolic rates (FCRs) were not altered significantly in any of the three lipoprotein fractions on pravastatin therapy. Further, pravastatin produced no consistent changes in LDL particle size, composition, or LDL subclass pattern. Thus pravastatin seemingly reduced input rates for all apo B-containing lipoproteins. Consistent with previous studies, this response was most likely the result of enhanced removal of nascent lipoproteins by increased activity of LDL receptors, although decreased synthesis of apo B in the liver is a possible second action.