Effects of combined therapy with lovastatin and colestipol in heterozygous familial hypercholesterolemia. Effects on kinetics of apolipoprotein B

This investigation was carried out in 10 male patients with heterozygous familial hypercholesterolemia to determine the effects of combined drug therapy with lovastatin and colestipol on the kinetics of apolipoprotein B (apo B) in low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Drug treatment produced reductions in plasma total cholesterol and LDL cholesterol averaging 41% and 48%, respectively. Levels of LDL apo B declined by only 34%, which resulted in a reduction in LDL cholesterol/apo B ratios. The major change in LDL apo B kinetics was a marked increase in fractional catabolic rate for LDL apo B, while production rates for LDL apo B were not changed. Combined drug therapy likewise produced a striking reduction in VLDL cholesterol. This change was associated with an increased clearance of a slowly catabolized fraction of VLDL apo B. Production rates for total VLDL apo B were unchanged. Overall, the combination of lovastatin and colestipol reduced plasma cholesterol and lipoprotein fractions to an acceptable range, and the primary mechanism appeared to be via an increase in the activity of LDL receptors and not by a reduction in production rates of lipoproteins.