Effect of treatment with simvastatin on serum cholesteryl ester transfer in patients on dialysis. PERFECT Study Collaborative Group.
BACKGROUND
Plasma cholesteryl ester transfer activity is increased in patients with chronic renal failure on dialysis who have elevated levels of apolipoprotein B (apoB)-containing lipoproteins. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, reduces levels of these lipoproteins but the effect of treatment on cholesteryl ester transfer activity in patients on dialysis remains to be determined.


METHODS
We measured serum newly synthesized cholesteryl ester transfer (NCET) activity, lecithin:cholesterol acyltransferase (LCAT) activity and serum lipid, lipoprotein and apolipoprotein concentrations before and immediately after 6 months treatment with simvastatin (10 mg daily, n = 24) or placebo (n = 29) in 53 patients with chronic renal failure receiving haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).


RESULTS
Simvastatin therapy significantly reduced serum cholesterol, LDL cholesterol, apoB concentrations, and both NCET (P = 0.001) and LCAT (P = 0.012) rates. The decrease in NCET activity was correlated significantly with the corresponding decrease in apoB concentration (r = 0.715, P < 0.001) and LCAT activity (r = 0.715, P < 0.001) during simvastatin therapy and was no longer significant when apoB concentration (P = 0.14) or LCAT activity (P = 0.07) were controlled.


CONCLUSIONS
These data show that simvastatin therapy reduces serum NCET rates, and suggest that this may be linked to the concomitant decrease in levels of apoB-containing lipoproteins which are acceptors of transferred cholesteryl esters, and to the decrease in serum LCAT rates in patients with chronic renal failure with treatment.
Walker
R J
RJ
Department of Medicine, University of Otago Medical School, Dunedin, New Zealand.
Sutherland
W H
WH
Walker
H L
HL
MacMahon
S
S
Robson
R A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002788:Cholesterol Esters / Q000097:blood*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D006435:Renal Dialysis; D019821:Simvastatin; D002785:Sterol O-Acyltransferase / Q000097:blood
D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008148:Lovastatin; D019821:Simvastatin; D002785:Sterol O-Acyltransferase