PLASMA-LIPOPROTEINS IN DIET-RESISTANT POLYGENIC AND FAMILIAL HYPERCHOLESTEROLEMIA - THE EFFECTS OF 3-HYDROXY-3-METHYLGLUTARIC ACID (HMGA, MEVALON

The effects of 3-hydroxy-3-methylglutaric acid (HMGA; Mevalon), a serum cholesterol-lowering agent, were studied in five patients with heterozygous familial hypercholesterolaemia (FH) and in 17 patients with polygenic hypercholesterolaemia. After 8-9 weeks of treatment (1 g twice daily) the mean reduction in total and LDL-cholesterol was -11.4% and -18.0% respectively in heterozygous FH. However, the response was markedly heterogeneous. In patients with polygenic hypercholesterolaemia, HMGA produced a considerably greater mean reduction in total and LDL-cholesterol (-14.4% and -19.0% respectively) and a significant reduction in total serum triglyceride concentration (-11.6%). In all patients HDL-cholesterol levels tended to decrease during treatment. In Type IIa polygenic hypercholesterolaemia a transitory slight increase in VLDL-cholesterol levels was also observed. The drug was well tolerated. No clinically significant changes in liver funtion occurred. HMGA appears to be a useful drug for the treatment of most patients with diet-resistant polygenic hypercholesterolaemia and of some patients with heterozygous FH. Hence, the genetic classification of the form of hypercholesterolaemia is to some extent predictive of the lipid-lowering effects of HMGA.