EFFECTS OF LOVASTATIN THERAPY ON VERY-LOW-DENSITY LIPOPROTEIN TRIGLYCERIDE-METABOLISM IN SUBJECTS WITH COMBINED HYPERLIPIDEMIA - EVIDENCE FOR REDUCED ASSEMBLY AND SECRETION OF TRIGLYCERIDE-RICH LIPOPROTEINS

We have previously reported decreased production rates of the major apolipoprotein B (apoB)-containing lipoproteins, very-low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) in patients with combined hyperlipidemia (CHL) during treatment with lovastatin. In the present study, we determined the effects of lovastatin therapy on VLDL triglyceride (TG) metabolism. Plasma VLDL turnover was determined in six CHL patients, before and during lovastatin therapy. 3H-triglyceride-glycerol-specific activity data derived from injection of 3H-glycerol were analyzed by compartmental modeling. The effects of lovastatin on VLDL TG metabolism were compared with those previously determined on VLDL apoB metabolism in these subjects. Lovastatin therapy was associated with decreased concentrations of VLDL TG in five of six patients and decreased VLDL apoB concentrations in all six. VLDL TG production rates (PR) decreased in five patients, with the mean for the group decreasing from 14.1 ± 7.1 to 10.3 ± 4.0 mg/kg/h (P < .05). VLDL apoB PR also decreased in five patients, with the mean decreasing from 21.8 ± 20.3 to 12.2 ± 9.0 mg/kg/d (P = .11). Changes in VLDL TG concentrations during lovastatin treatment were correlated with changes in VLDL apoB concentrations (r = .74, P = .09) and in VLDL TG PR (r = .91, P = .01). Changes in VLDL TG PR were also related to changes in VLDL apoB PR (r = .62, P = NS). There were no consistent changes in the fractional catabolic rates of either VLDL TG or VLDL apoB during lovastatin therapy. These findings suggest that, in CHL patients, reductions in VLDL TG concentrations during lovastatin therapy are usually associated with decreased VLDL TG PR, and these effects parallel concomitant reductions in VLDL apoB PR. Taken together with our previous finding of reduced total apoB secretion into plasma during lovastatin treatment, these results support the hypothesis that the overall hypolipidemic effects of lovastatin in patients with CHL are due to decreased assembly and secretion of apoB-containing lipoproteins. © 1992.