Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: Results From the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial
Fraley AE et al. – In pts with acute coronary syndromes (ACS), baseline levels of oxidative biomarkers varied by specific cardiovascular disease (CVD) risk factors and were largely independent of inflammatory biomarkers. Atorvastatin uniformly increased oxidized phospholipids (OxPL)/apolipoprotein B particles (apoB) levels in all subgroups. Future studies must assess whether the increase in OxPL/apoB levels reflects the benefit of effective therapeutic interventions and prediction of new CVD events. Methods- Study of relationship between oxidative biomarkers, CVD risk factors, and inflammatory and thrombosis biomarkers
- Measurement of OxPL/apoB, lipoprotein (a) [Lp(a)], and oxidized low-density lipoprotein (OxLDL) biomarkers
- OxLDL biomarkers: immunoglobulin (Ig)G and IgM autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL) and IgG and IgM apoB-100 immune complexes (IC/apoB)
- Assessment at baseline and after 16 wks of treatment with atorvastatin 80 mg/day or placebo
- Subjects: 2,342 ACS pts enrolled in MIRACL
Results- At baseline, potentially atheroprotective IgM autoantibodies and IgM IC/apoB lower in male pts, diabetic pts, and pts age >65 yrs
- Higher levels of OxPL/apoB, Lp(a), and OxLDL biomarkers for pts with LDL levels greater vs less than the median (122 mg/dL)
- Atorvastatin resulted in significantly larger changes in all biomarkers in female pts, pts age <65 yrs, pts with LDL cholesterol <122 mg/dl, nonsmokers, and nondiabetic pts
- A significant increase in OxPL/apoB in response to atorvastatin in all 20 subgroups
- Weak or no significant correlations between all OxLDL biomarkers and C-reactive protein, serum amyloid A, tissue plasminogen activator, interleukin-6, intercellular adhesion molecule, vascular cell adhesion molecule, P-selectin, and E-selectin at randomization and 16 wks
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