The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans.
OBJECTIVE
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-iPF(2 alpha)-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-iPF(2 alpha)-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.
Ky
Bonnie
B
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA.
Burke
Anne
A
Tsimikas
Sotirios
S
Wolfe
Megan L
ML
Tadesse
Mahlet G
MG
Szapary
Philippe O
PO
Witztum
Joseph L
JL
FitzGerald
Garret A
GA
Rader
Daniel J
DJ
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000187:drug effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D000069059:Atorvastatin; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001323:Autoantibodies; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D010743:Phospholipids; D011758:Pyrroles; D000069059:Atorvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D017035:Pravastatin