title: Lipid and apoprotein changes during atorvastatin up-titration in hemodialysis patients with hypercholesterolemia: a placebo-controlled study.
abstract: BACKGROUND
  Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich, apoprotein B-containing "remnant" lipoproteins, small dense low-density lipoprotein, and low levels of high-density lipoprotein. They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin, a potent, broadacting lipid regulator. This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients, to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup.
  
  
  METHODS
  In this randomized, placebo-controlled, double-blind study in hemodialysis patients with hypercholesterolemia (n = 42, mean total cholesterol 243 +/- 33 mg/dl (6.3 +/- 0.8 mmol/l)), the efficacy of 4-weekly increasing doses of atorvastatin (10 - 40 mg daily) was investigated. Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions.
  
  
  RESULTS
  Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin (total cholesterol -33%, low-density lipoprotein cholesterol -43% after 12 weeks), while high-density lipoprotein cholesterol remained unchanged. Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg, while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III. At week 12, the fraction of small dense low-density lipoprotein was significantly reduced from 23% - 18%, and apoprotein B-containing intermediate-density lipoproteins were no longer detectable.
  
  
  CONCLUSIONS
  In conclusion, atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis. Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated. Further prospective studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality.
authors.affiliation: ZNA - Jan Palfijn, Merksem, Brussels, Belgium. robert.lins@village.uunet.be
authors.forename: R L
authors.initials: RL
authors.lastname: Lins
authors.forename: K E
authors.initials: KE
authors.lastname: Matthys
authors.forename: J M
authors.initials: JM
authors.lastname: Billiouw
authors.forename: M
authors.initials: M
authors.lastname: Dratwa
authors.forename: P
authors.initials: P
authors.lastname: Dupont
authors.forename: N H
authors.initials: NH
authors.lastname: Lameire
authors.forename: P C
authors.initials: PC
authors.lastname: Peeters
authors.forename: J C
authors.initials: JC
authors.lastname: Stolear
authors.forename: C
authors.initials: C
authors.lastname: Tielemans
authors.forename: B
authors.initials: B
authors.lastname: Maes
authors.forename: G A
authors.initials: GA
authors.lastname: Verpooten
authors.forename: J
authors.initials: J
authors.lastname: Ducobu
authors.forename: Y A
authors.initials: YA
authors.lastname: Carpentier
mesh_terms: D000368:Aged; D001055:Apolipoproteins B / Q000097:blood* / Q000187:drug effects; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage*; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin