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Letter regarding article by Tsimikas et al, "high-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial".

Circulation (Impact Factor: 14.95). 06/2005; 111(18):e284-5; author reply e284-5. DOI: 10.1161/01.CIR.0000164264.00913.6D
Source: PubMed

ABSTRACT predominantly associated with Lp(a), 2 the increased OxPL/apoB ratio could be explained by the shift in the Lp(a)/LDL ratio. Similarly, in the placebo-treated group the decreased OxPL/apoB ratio results from a decrease in Lp(a) relative to LDL. It is therefore unlikely that the OxPL/apoB ratio is a surrogate marker of net removal of OxPL from the vessel wall. Moreover, the observed 30% decrease in total plasma apoB-OxPL also argues against an increased net efflux of OxPL from the vessel wall. Recently, using the OxLDL assay from Mercodia in which an oxidation epitope associated with apoB is detected with mono- clonal antibody 4E6, we found that atorvastatin (80 mg/d) and simvastatin (40 mg/d) reduced total plasma Ox-apoB (43% and 35%, respectively) in patients with familial hypercholesterol- emia from the ASAP study.3 Interestingly, we observed no change in the Ox-apoB/apoB ratio when we used the noncom- petitive version of the kit, in which the immobilized antibody captures Ox-apoB from the sample. We did, however, observe a small increase in the Ox-apoB/apoB ratio (18% for atorvastatin, 13% for simvastatin) when we used the competitive version, which unlike the noncompetitive version is sensitive to the number of oxidation epitopes associated with apoB. In addition, the increase in Ox-apoB/apoB ratio can be explained by an increase in Lp(a) relative to LDL. To further address this question, measurements of OxLDL with E06 and 4E6 in well- designed assays (eg, in isolated Lp(a) particles) at different time points after the start of statin treatment are required.

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    ABSTRACT: OBJECTIVES: The goal of this study was to examine the prospective association between oxidation-specific biomarkers, primarily oxidized phospholipids (OxPL) on apolipoprotein B-100-containing lipoproteins (OxPL/apoB) and lipoprotein (a) [Lp(a)], and risk of peripheral artery disease (PAD). As secondary analyses, we examined indirect measures of oxidized lipoproteins, including autoantibodies to malondialdehyde-modified low density lipoprotein (MDA-LDL) and apolipoprotein B-100 immune complexes (ApoB-IC). BACKGROUND: Biomarkers to predict the development of PAD are lacking. OxPL circulate in plasma, are transported by Lp(a), and deposit in the vascular wall and induce local inflammation. METHODS: The study population included two parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study (1994-2008) and 144 women within the Nurses' Health Study (1990-2010) with incident confirmed cases of clinically significant PAD, matched 1:3 to controls. RESULTS: Levels of OxPL/apoB were positively associated with risk of PAD in men and women: pooled relative risk (RR) 1.37, 95% CI, 1.19-1.58 for each 1-standard deviation increase after adjusting age, smoking, fasting status, month of blood draw, lipids, body mass index, and other cardiovascular disease risk factors. Lp(a) was similarly associated with risk of PAD (pooled adjusted RR, 1.36; 95% CI, 1.18-1.57 for each 1-standard deviation increase). Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD. CONCLUSIONS: OxPL/apoB were positively associated with risk of PAD in men and women. The major lipoprotein carrier of OxPL, Lp(a), was also associated with risk of PAD, reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a).
    Journal of the American College of Cardiology 03/2013; · 15.34 Impact Factor

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