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A biomarker panel for peripheral arterial disease

Vermillion, Inc., Fremont, CA, USA

Andrew M Wilson

Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

Fujun Zhang

Vermillion, Inc., Fremont, CA, USA

Nathan Harris

Vermillion, Inc., Fremont, CA, USA

Kim A Edwards

Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

Jeffrey W Olin

Zena and Michael A Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, NY, USA

John P Cooke

Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA john.cooke{at}stanford.edu

Abstract

Peripheral arterial disease (PAD) is common, but often not diagnosed. A biomarker index would be useful to raise suspicion of PAD, so as to trigger appropriate vascular testing and management. The study comprised 540 individuals: 197 individuals with both coronary artery disease and peripheral arterial disease (CAD + PAD); 81 with CAD only; and 262 with no hemodynamically significant disease (NHSD) of the coronary or peripheral arteries. Multiple linear regression was performed to generate a biomarker panel score that could predict ankle–brachial index (ABI). Logistic regression was used to investigate the relationship between disease status and the panel score as well as other risk factors (e.g. age, diabetes status, smoking status). ROC analysis was performed to test the prediction power of the biomarker panel score. Among the plasma markers tested, beta 2 microglobulin (β2M) and cystatin C had the highest correlation with ABI, and higher than any of the conventional risk factors of age, smoking status, and diabetes status. A biomarker panel score derived from β2M, cystatin C, hsCRP, and glucose had an increased association with PAD status (OR = 12.4, 95% confidence interval (CI) 6.6–23.5 for highest vs lowest quartile), which was still significant after adjusting for known risk factors (OR = 7.3, 95% CI 3.6–14.9 for highest vs lowest quartile). In conclusion, after taking into account the traditional risk factors for PAD, a biomarker panel comprising β2M, cystatin C, hsCRP, and glucose adds useful information to assess the risk of disease.

Key Words: beta 2 microglobulin • C-reactive peptide • cystatin C • glucose • proteomics

Vascular Medicine, Vol. 13, No. 3, 217-224 (2008)
DOI: 10.1177/1358863X08089276


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