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.

Abstract

OBJECTIVES:

This study sought to define the relationship between oxidative biomarkers, cardiovascular disease (CVD) risk factors, and inflammatory and thrombosis biomarkers.

BACKGROUND:

Elevated levels of oxidized phospholipids (OxPL) on apolipoprotein B particles (apoB) represent a novel biomarker of CVD. Previous studies suggest that an increase in OxPL/apoB reflects a positive response to statins and a low-fat diet.

METHODS:

This study measured OxPL/apoB, lipoprotein (a) [Lp(a)], and oxidized low-density lipoprotein (OxLDL) biomarkers, consisting of immunoglobulin (Ig)G and IgM autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL) and IgG and IgM apoB-100 immune complexes (IC/apoB), at baseline and after 16 weeks of treatment with atorvastatin 80 mg/day or placebo in 2,342 patients with acute coronary syndromes (ACS) enrolled in the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial.

RESULTS:

At baseline, potentially atheroprotective IgM autoantibodies and IgM IC/apoB were lower in male patients, diabetic patients, and patients >65 years of age. Patients with an LDL level greater than the median (122 mg/dl) had higher levels of OxPL/apoB, Lp(a), and OxLDL biomarkers compared with those who had an LDL level less than the median. Atorvastatin resulted in significantly larger changes in all biomarkers in female patients, patients age <65 years, patients with LDL cholesterol <122 mg/dl, nonsmokers, and nondiabetic patients (p < 0.0001 for all). In particular, a significant increase in OxPL/apoB in response to atorvastatin was noted in all 20 subgroups evaluated. Weak or no significant correlations were noted 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 weeks.

CONCLUSIONS:

In patients with ACS, baseline levels of oxidative biomarkers varied according to specific CVD risk factors and were largely independent of inflammatory biomarkers. Atorvastatin uniformly increased OxPL/apoB levels in all subgroups studied. Future studies are warranted to assess whether the increase in OxPL/apoB levels reflects the benefit of effective therapeutic interventions and prediction of new CVD events.

• Authors: Alexander E Fraley, Gregory G Schwartz, Anders G Olsson, Scott Kinlay, Michael Szarek, Nader Rifai, Peter Libby, Peter Ganz, Joseph L Witztum, Sotirios Tsimikas, MIRACL Study Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 53 Issue 23 Pg. 2186-96 (Jun 09 2009) ISSN: 1558-3597 [Electronic] United States
• PMID: 19497447 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Anticholesteremic Agents
• Apolipoproteins B
• Autoantibodies
• Biomarkers
• Cholesterol, LDL
• Heptanoic Acids
• Immunoglobulin G
• Immunoglobulin M
• Lipoprotein(a)
• Phospholipids
• Pyrroles
• Reactive Oxygen Species
• Atorvastatin

Topics

• Acute Coronary Syndrome (drug therapy, immunology, physiopathology)
• Aged
• Aged, 80 and over
• Anticholesteremic Agents (therapeutic use)
• Apolipoproteins B (chemistry, immunology, metabolism)
• Atorvastatin
• Autoantibodies (analysis)
• Biomarkers (analysis)
• Cholesterol, LDL (analysis, immunology, metabolism)
• Cohort Studies
• Female
• Heptanoic Acids (therapeutic use)
• Humans
• Immunoglobulin G (analysis)
• Immunoglobulin M (analysis)
• Inflammation (physiopathology)
• Lipoprotein(a) (analysis)
• Male
• Middle Aged
• Oxidation-Reduction
• Phospholipids (analysis, metabolism)
• Pyrroles (therapeutic use)
• Reactive Oxygen Species
• Risk Factors
• Thromboembolism