Relationship between biomarkers of oxidized low-density lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) study.
OBJECTIVE
This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume.


BACKGROUND
Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known.


METHODS
In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed.


RESULTS
There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume.


CONCLUSIONS
Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.
Choi
Seung Hyuk
SH
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chae
Andrew
A
Miller
Elizabeth
E
Messig
Michael
M
Ntanios
Fady
F
DeMaria
Anthony N
AN
Nissen
Steven E
SE
Witztum
Joseph L
JL
Tsimikas
Sotirios
S
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000097:blood* / Q000000981:diagnostic imaging* / Q000188:drug therapy; D000069059:Atorvastatin; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism*; D017023:Coronary Angiography; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin / Q000627:therapeutic use; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use; D012107:Research Design
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001323:Autoantibodies; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017270:Lipoprotein(a); D010743:Phospholipids; D011758:Pyrroles; D008315:Malondialdehyde; D000069059:Atorvastatin; D017035:Pravastatin