What is the Role of Biomarkers in Identifying Risk in Patients with Peripheral Artery Disease?

Monica Bertoia, PHD (Disclosure)

Sotirios Tsimikas, M.D., F.A.C.C. (Disclosure)

August 05, 2013

Although treatments such as statins and anti-platelet agents effectively slow the progression of peripheral artery disease (PAD) as well as reduce associated morbidity and mortality, PAD is often asymptomatic and can remain untreated until it reaches more advanced stages. Biomarkers to predict the development of PAD are therefore extremely important. Several biomarkers have been identified that are associated with risk of PAD, and include inflammatory cytokines, markers of endothelial dysfunction, modulators of angiogenesis, lipoproteins, coagulation factors, and markers of oxidative stress1.

Evidence suggests that oxidative stress plays a significant role in the etiology of atherosclerosis2; however many biomarkers of oxidation are lacking in terms of reliability, accuracy, cost-effectiveness, or ease of measurement. Furthermore, many biomarkers of oxidation have not been evaluated as potential risk factors for PAD. In our recent study3, we examined the association between levels of oxidized phospholipids (OxPL) on apolipoprotein B-100-containing lipoproteins (OxPL/apoB), a marker of lipid oxidation, and risk of PAD.

We found a positive association between pro-inflammatory OxPL/apoB, with men and women in the third highest tertile of OxPL/apoB having approximately double the risk of PAD compared to those in the lowest tertile. Lipoprotein (a) [Lp(a)], the main carrier of OxPL, was also associated with risk of PAD, indicating that OxPL play a key role in the pathophysiology of atherosclerosis mediated by Lp(a). We also found that levels of OxPL/apoB were not associated with traditional cardiovascular disease risk factors including biomarkers (triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, hemoglobin A1c, cystatin C, and homocysteine), with the exception of Lp(a). OxPL therefore represent a unique oxidation-specific biomarker that appears to be valid, cost-effective, and measurable in plasma collected by standard protocols.

  1. 1. Cooke JP, Wilson, AM. Biomarkers of peripheral arterial disease. J Am Coll Cardiol 2010:55; 2017-23.
  2. 2. Berliner JA, Navab M, Fogelman AM,et al., Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91:2488-96.
  3. 3. Bertoia ML, Pai JK, Lee JH, et al. Oxidation-specific biomarkers and risk of peripheral artery disease. J Am Coll Cardiol 2013; 61:2169-79.


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