Influence of lovastatin therapy on metabolism of low density lipoproteins in mixed hyperlipidaemia.

To determine the mechanisms whereby HMG-CoA reductase inhibitors lower the levels of low density lipoproteins (LDL) in patients with mixed hyperlipidaemia, LDL turnover studies were conducted in 12 such patients during placebo and then during treatment with lovastatin. Drug therapy reduced total cholesterol and triglyceride concentrations by 33% and 32%, respectively. During lovastatin therapy, LDL-cholesterol levels fell by 37%, and LDL-apo B concentrations decreased by an average of 29%. The decrease in LDL-apo B concentrations on lovastatin therapy was largely due to an increase in fractional catabolic rates (FCRs) for LDL apo B. The average increase in FCRs was 34%, whereas transport rates (production rates) for LDL apo B remained unchanged. These results strongly suggest that an increase in LDL-receptor activity is the major mechanism whereby LDL levels are lowered during lovastatin therapy. The data do not indicate that this drug inhibited the input of apo B-containing lipoproteins, which would have been expected to result in a decrease in the rate of production of LDL.