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J Am Coll Cardiol, 2008; 51:1653-1662, doi:10.1016/j.jacc.2008.01.026 © 2008 by the American College of Cardiology Foundation |


* Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania
University of California San Diego, La Jolla, California.
Manuscript received September 28, 2007; revised manuscript received January 24, 2008, accepted January 29, 2008.
* Reprint requests and correspondence: Dr. Daniel J. Rader, University of Pennsylvania, 421 Curie Boulevard, Room 654 BRB, Philadelphia, Pennsylvania 19104-6160. (Email: rader{at}mail.med.upenn.edu).
Objectives: The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma.
Background: Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, but their effects on circulating biomarkers of oxidative stress are not well-defined.
Methods: Hypercholesterolemic subjects (n = 120, ages 21 to 80 years with LDL-C 130 to 220 mg/dl) were randomized in a double-blind, parallel design to pravastatin 40 mg/day (prava40), atorvastatin 10 mg/day (atorva10), atorvastatin 80 mg/day (atorva80), or placebo. At baseline and 16 weeks, urinary isoprostanes (8, 12-iso-iPF2
-VI isoform), plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), Mercodia oxidized LDL (OxLDL) with antibody 4E6, oxidized phospholipids/apolipoprotein B-100 particle (OxPL/apoB) with antibody E06, immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL, and apolipoprotein B (apoB)-immune complexes (IC) were measured.
Results: After 16 weeks, there were no significant changes in urinary 8, 12-iso-iPF2
-VI. The Lp-PLA2 and OxLDL were reduced in statin-treated groups, but after adjusting for apoB, only prava40 led to a reduction in Lp-PLA2 (–15%, p = 0.008) and atorva10 to a decrease in OxLDL (–12.9%, p = 0.01). The OxPL/apoB increased 25.8% (p < 0.01) with prava40 and 20.2% (p < 0.05) with atorva80. There were no changes in MDA-LDL autoantibodies, but significant decreases in IC were noted.
Conclusions: This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects. Future outcome studies should collectively assess various oxidative markers to define clinical utility.
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