Influence of combined therapy with mevinolin and interruption of bile-acid reabsorption on low density lipoproteins in heterozygous familial hypercholesterolemia.
Patients with heterozygous familial hypercholesterolemia have a 50% deficiency of receptors for plasma low density lipoproteins (LDL) that induces a marked increase in plasma LDL levels. Two therapeutic measures that seem to increase the synthesis of LDL receptors are interruption of the enterohepatic circulation of bile acids with either bile-acid sequestrants or the ileal-exclusion operation, and competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase with mevinolin or compactin. To determine the effectiveness of this combination and the mechanisms of lowering LDL levels, we measured turnover rates of LDL apoprotein (apo-LDL) before and during treatment with mevinolin and colestipol in eight patients with heterozygous familial hypercholesterolemia. Drug therapy reduced LDL cholesterol levels by an average of 52%; this response was due to a 40% increase in fractional catabolic rate of apo-LDL and a 26% decrease in its production rate. A similar response was obtained in two patients who had previously had an ileal-exclusion operation for severe hypercholesterolemia and who were treated with mevinolin.
D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003084:Colestipol / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D004764:Enterohepatic Circulation; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D007082:Ileum / Q000601:surgery; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood*; D008148:Lovastatin; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*
D001053:Apolipoproteins; D001647:Bile Acids and Salts; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D009281:Naphthalenes; C010681:apolipoprotein LDL, human; D002784:Cholesterol; D008148:Lovastatin; D003084:Colestipol