Improvement of serum oxidation by pravastatin might be one of the mechanisms by which endothelial function in dilated coronary artery segments is ameliorated.
BACKGROUND
Oxidation susceptibility of lipids in vitro is considered to reflect the exposure of lipids to oxidation stress in vivo which is related to cardiovascular morbidity. This study examined the effect of pravastatin therapy on serum oxidation susceptibility, particularly in relation to endothelial function of coronary arteries.


METHODS
The participants were recruited from the Pravastatin-Related Effects Following Angioplasty on Coronary Endothelium trial, a double-blinded, placebo-controlled, randomized, multi-center study designed to analyze the effect of pravastatin treatment on endothelial function in previously dilated and normal coronary arteries. Serial, graded, intra-coronary acetylcholine infusions were used to assess endothelial function. In vitro, copper-induced, serum oxidation parameters were determined at randomization and at time of coronary endothelial function assessment.


RESULTS
Oxidation parameters were determined in 45 patients (pravastatin 23, placebo 22). Pravastatin therapy significantly improved serum oxidation lag time (+8%, P<0.05), maximal diene formation rate (-22%, P<0.01) and total amount of dienes formed after 5 h (-16%, P<0.01). These parameters remained essentially unchanged in the placebo group. Acetylcholine-evoked responses were positively correlated to therapy-induced change in serum oxidation susceptibility in the dilated segment group (r2=0.56, P=0.006).


CONCLUSIONS
Pravastatin's beneficial effect on endothelial dysfunction of dilated coronary segments may be secondary to pravastatin's improvement of oxidation susceptibility.
Mulder
Han J G H
HJ
Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300RC Leiden, The Netherlands. j.g.h.mulder@lumc.nl
Schalij
Martin J
MJ
van der Laarse
Arnoud
A
Hollaar
Leny
L
Zwinderman
Aeilko H
AH
Bruschke
Albert V G
AV
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001769:Blood / Q000378:metabolism*; D003327:Coronary Disease / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D010084:Oxidation-Reduction; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
D000924:Anticholesteremic Agents; D017035:Pravastatin; D000109:Acetylcholine