Effect of fluvastatin on apolipoprotein-defined lipoprotein subclasses in patients with chronic renal insufficiency.
According to the concept of apolipoprotein (apo)-defined lipoproteins, apoA-I-containing lipoproteins consist of two subclasses referred to as lipoprotein A-I (LpA-I) and lipoprotein A-I:A-II (LpA-I:A-II), and apoB-containing lipoproteins of five subclasses, namely lipoprotein B (LpB), lipoprotein B:C (LpB:C), lipoprotein B:E (LpB:E), lipoprotein B:C:E (LpB:C:E), and lipoprotein A-II:B:C:D:E (LpA-II:B:C:D:E). The purpose of this study was to determine the levels of apoA-I- and apoB-containing lipoprotein subclasses before and after fluvastatin treatment of patients with chronic renal insufficiency. ApoA-I- and apoB-containing lipoprotein subclasses were measured in 15 patients with chronic renal failure and 15 asymptomatic subjects. The effect of fluvastatin on lipoprotein subclasses was determined in a randomized, double-blind, placebo-controlled, two-way, treatment period crossover study. Patients were administered fluvastatin 40 mg/day or placebo during 8 weeks in a randomized order. Patients were characterized by significantly higher levels of LpB (P < 0.001), LpB:C (P < 0.001), and LpB:E (P < 0.05), and slightly higher levels of LpB:C:E and LpA-II:B:C:D:E than controls. The levels of LpA-I:A-II were significantly lower (P < 0.01) in patients than controls. Fluvastatin treatment reduced all apoB-containing subclasses, but only the reduced level of LpB subclass was statistically significant (P < 0.02). The levels of LpA-I and LpA-I:A-II were not affected. Fluvastatin treatment reduced and normalized LpB and LpB:E subclasses. Although slightly reduced, the levels of markedly atherogenic LpB:C subclass were not normalized. The potential role of LpB:C on the progression of coronary artery disease in chronic renal insufficiency remains to be determined in future studies.
Alaupovic
P
P
Lipid and Lipoprotein Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, 73104, USA. alaupovicp@omrf.ouhsc.edu
Attman
P-O
PO
Knight-Gibson
C
C
Mulec
H
H
Weiss
L
L
Samuelsson
O
O
D000368:Aged; D001055:Apolipoproteins B / Q000097:blood / Q000145:classification / Q000187:drug effects*; D001827:Body Height; D015992:Body Mass Index; D015331:Cohort Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood / Q000145:classification / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D001055:Apolipoproteins B; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008074:Lipoproteins; D000077340:Fluvastatin