Pravastatin in heterozygous familial hypercholesterolemia: low-density lipoprotein (LDL) cholesterol-lowering effect and LDL receptor activity on skin fibroblastS.
The cholesterol-lowering effect of provastatin, a new competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, was studied in 10 patients with heterozygous familial hypercholesterolemia (FH). Residual low-density lipoprotein receptor (LDL-R) activity was also evaluated in cultured skin fibroblasts prior to treatment, and showed a wide range of reduction from 30% to 70% of the normal value. Treatment with pravastatin 40 mg once daily reduced total and LDL cholesterol (LDL-C) after 6 months by 19.7% and 25.4%, respectively (P less than .001). Serum apolipoprotein (apo) B levels decreased significantly by 29.1% (P less than .001). No significant changes were observed in mean serum total triglycerides or high-density lipoprotein cholesterol (HDL-C) levels. A positive correlation between residual LDL-R activity and maximum percent reduction of LDL-C levels was observed (r = .676, P less than .05). No clinically important side effects were recorded and the treatment was well tolerated. Thus, pravastatin effectively reduces LDL in heterozygous FH, and this effect appears to be related to LDL-R status.
Gaddi
A
A
Cattedra di Medicina Interna e Centro Aterosclerosi, Università di Bologna, Italy.
Arca
M
M
Ciarrocchi
A
A
Fazio
S
S
D'Alò
G
G
Tiozzo
R
R
Descovich
G C
GC
Calandra
S
S
D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D012044:Regression Analysis; D012867:Skin / Q000378:metabolism* / Q000473:pathology
D008078:Cholesterol, LDL; D008055:Lipids; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D017035:Pravastatin