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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.
J Am Coll Cardiol. 2009 Jun 09; 53(23):2186-96.JACC

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+Show Affiliations

University of California San Diego, 92093-0682, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19497447

Citation

Fraley, Alexander E., et al. "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." Journal of the American College of Cardiology, vol. 53, no. 23, 2009, pp. 2186-96.
Fraley AE, Schwartz GG, Olsson AG, et al. 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. J Am Coll Cardiol. 2009;53(23):2186-96.
Fraley, A. E., Schwartz, G. G., Olsson, A. G., Kinlay, S., Szarek, M., Rifai, N., Libby, P., Ganz, P., Witztum, J. L., & Tsimikas, S. (2009). 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. Journal of the American College of Cardiology, 53(23), 2186-96. https://doi.org/10.1016/j.jacc.2009.02.041
Fraley AE, et al. 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. J Am Coll Cardiol. 2009 Jun 9;53(23):2186-96. PubMed PMID: 19497447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Fraley,Alexander E, AU - Schwartz,Gregory G, AU - Olsson,Anders G, AU - Kinlay,Scott, AU - Szarek,Michael, AU - Rifai,Nader, AU - Libby,Peter, AU - Ganz,Peter, AU - Witztum,Joseph L, AU - Tsimikas,Sotirios, AU - ,, PY - 2008/10/21/received PY - 2009/02/05/revised PY - 2009/02/11/accepted PY - 2009/6/6/entrez PY - 2009/6/6/pubmed PY - 2009/6/25/medline SP - 2186 EP - 96 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 53 IS - 23 N2 - 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. SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/19497447/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(09)00928-0 DB - PRIME DP - Unbound Medicine ER -