Oxidation-Specific Biomarkers and Risk of Peripheral Artery Disease

Study Questions:

What is the 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)?


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. The investigators used conditional logistic regression, conditioning on matching factors, to estimate odds ratios for PAD according to level of OxPL/apoB and present estimates adjusted for matching factors and additionally for other PAD risk factors.


Levels of OxPL/apoB were positively associated with risk of PAD in men and women: pooled relative risk (RR), 1.37; 95% confidence interval (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.


The authors concluded that OxPL/apoB levels were positively associated with risk of PAD in men and women.


This study suggests that OxPL/apoB levels are positively associated with risk of PAD in men and women, with no appreciable attenuation after adjustment for conventional risk factors. In contrast, there were no consistent relationships of indirect measures of oxidized lipoproteins such as autoantibodies to MDA-LDL and apoB-immune complexes with risk of PAD. Future research should explore the mechanisms that link oxidation to risk of PAD and test whether novel therapies that reduce levels of OxPL may prevent the development of atherosclerotic diseases such as PAD.

Clinical Topics: Dyslipidemia, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Advanced Lipid Testing, Lipid Metabolism, Novel Agents

Keywords: Follow-Up Studies, Lipoprotein(a), Oxidation-Reduction, Oxytocin, Peripheral Arterial Disease, Risk Factors, Autoantibodies, Body Mass Index, Case-Control Studies, Biological Markers, Benzimidazoles, Troponin I, Cardiology, Cardiovascular Diseases

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