Peripheral arterial disease ("PAD") represents atherosclerosis of the lower extremities and is generally reflective of systemic atherosclerotic disease and is therefore a risk factor for adverse cardiac events such as myocardial infarction and stroke. This disease affects between 8-12 million Americans, and the number of people diagnosed with PAD is expected to increase concurrently with the rising number of people diagnosed with diabetes. The American Heart Association and the American College of Cardiology have identified three demographics at risk for PAD: smokers 50 years of age or older; diabetics 50 years of age or older; and the elderly 70 years of age or older. Collectively, this represents tens of millions of Americans.

PAD is most commonly diagnosed using the ankle-brachial index ("ABI"), which is performed using a handheld Doppler. Blood pressures are measured in the arm and at the ankles and the ratio (ankle/arm) is calculated. Non-affected individuals should have a ratio of 0.9 or greater, while individuals with a ratio of less than 0.9 are defined as having PAD. Although the ABI has good sensitivity and specificity for PAD, its implementation into routine clinical practice has been hampered by poor physician adoption, generally because of the need to utilize special equipment by a specially trained technician and the need to have the patient lie supine prior to the administration of this test. Additionally, studies have shown that the ABI is often performed incorrectly. Therefore, a blood test that can be more routinely implemented would be beneficial in identifying people at increased risk for PAD. In collaboration with Dr. John Cooke at Stanford, Vermillion has performed both an initial discovery study and a first validation study that has resulted in the identification blood markers that could assist in the diagnosis of PAD. These findings form the basis of a novel blood diagnostic test for PAD.

The results of these studies, including the publication of two blood markers for PAD, were published in the August 2007 on-line issue of the peer-reviewed journal Circulation, which is published by the American Heart Association (the "AHA"). Independent validation of these initial findings was subsequently published in the peer-reviewed journal Vascular Medicine in 2008. This study, which encompassed 540 individuals, confirmed the elevation of the two biomarkers in subjects with PAD. Moreover, the study showed that a panel of markers improved the identification of subjects with PAD and was complementary to available data, including the AHA risk score. In this study, subjects with a moderate AHA risk score but elevated PAD biomarker score had almost an 8 times increased likelihood of having PAD than if they had a normal PAD biomarker score.

Ongoing efforts are aimed at further validating these biomarkers in combination with additional cardiovascular biomarkers as well as a prospective study in a general practice setting. Quest has accepted the PAD test as a development program under the terms of the Amended Strategic Alliance Agreement.

Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies
Wilson AM, Kimura E, Harada RK, Nair N, Narasimhan B, Meng XY, Zhang F, Beck KR, Olin JW, Fung ET, Cooke JP.
Circulation. 2007 Sep 18;116(12):1396-403. Epub 2007 Aug 27.

A biomarker panel for peripheral arterial disease.
Fung ET, Wilson AM, Zhang F, Harris N, Edwards KA, Olin JW, Cooke JP.
Vasc Med. 2008 Aug;13(3):217-24.