Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins, C-reactive protein and in vivo oxidized LDL.
BACKGROUND
Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-stage renal disease (ESRD). Dyslipidemia may be a major contributor in this process and can be influenced by lipid-lowering drugs (statins). Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP).


METHODS
We evaluated in a single-blind randomized trial of 28 ESRD patients on hemodialysis, the dose-depending effects of both atorvastatin and simvastatin on lipids, lipoproteins, LDL particle heterogeneity, high sensitive-CRP, and markers of in vivo LDL oxidation.


RESULTS
Both statin therapies significantly lowered total plasma cholesterol and LDL-cholesterol concentrations to the same extent, whereas reduction in the concentrations of triglyceride-rich particles was less pronounced. Furthermore, statin therapy reduced LDL cholesterol in all LDL subfractions, without altering the overall LDL particle density. After both statins plasma hs-CRP concentrations were not significantly reduced; parameters of in vivo LDL oxidation (plasma ox-LDL concentration and the oxidation level of isolated LDL), were significantly decreased. Autoantibodies against ox-LDL, however, did not change during this trial period.


CONCLUSIONS
These results show that atorvastatin and simvastatin exhibit comparable favourable effects on lipid profiles in ESRD. Moreover, the reduction of in vivo oxidatively modified LDL as shown in this ESRD population, may indicate that these statins exhibit favourable effects on oxidative stress in vivo.
van den Akker
Judith M
JM
Department of Internal Medicine, Rijnstate Hospital of Arnhem, Arnhem, The Netherlands.
Bredie
Sebastian J H
SJ
Diepenveen
Sabine H A
SH
van Tits
Lambertus J H
LJ
Stalenhoef
Anton F H
AF
van Leusen
Rob
R
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects*; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D008075:Lipoproteins, HDL / Q000032:analysis / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011758:Pyrroles / Q000008:administration & dosage*; D012016:Reference Values; D006435:Renal Dialysis / Q000379:methods; D018570:Risk Assessment; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin