Predicting Treatment Outcomes in Patients With Peripheral Artery Disease

Leg Bypass Surgery, Angioplasty and Stents Currently Fail Up to 50 Percent of the Time

Vascular Cures, a leading nonprofit investing in research to develop breakthrough treatments for vascular disease, recently announced results that indicate there may be a genetic basis for the varying outcomes of bypass surgery in the legs. Results were presented by Michael S. Conte, MD, of the University of California, San Francisco, at the 2011 Society for Vascular Surgery Annual Meeting.

pipesBypass surgery, angioplasty and stents are all used to treat blockages caused by peripheral artery disease (PAD). Current estimates are that more than 8 million Americans have PAD, a condition that can produce severe disability and lead to amputation. Hundreds of thousands of procedures are performed each year in the U.S. to improve leg circulation in patients suffering from PAD, yet up to half of these fail within a few years due to excessive scarring that leads to reduced blood flow. The reasons for the variability in the outcome of PAD treatments have been poorly understood.

Led by vascular surgeons Dr. Conte and Alec Clowes, MD, at the University of Washington, the team demonstrated a potential genetic basis for why some patients experience blockage of their bypass grafts faster and more frequently than others.

“The results of this study, together with similar findings in a Dutch study of patients who underwent coronary stent angioplasty (van Tiel et al, 2009), strongly support the hypothesis that the formation of scar tissue in blood vessels is genetically regulated by the gene p27,” stated Dr. Conte.

Dr. Conte is chief of UCSF’s Division of Vascular and Endovascular Surgery and chief medical officer of Vascular Cures. Dr. Clowes is professor of surgery at the University of Washington and vice chair for research in the Department of Surgery.

“These studies represent a major breakthrough in our understanding of arteries closing after angioplasty and bypass grafting,” added Dr. Clowes. “More importantly, they may help us identify patients at increased risk of treatment failures. These results may also accelerate drug development to prevent renarrowing of vascular reconstructions.”

Members of the Vascular Cures Research Network, Dr. Conte and Dr. Clowes performed a gene association study in a group of 204 patients who had undergone leg vein bypass grafting, testing them for a common variation of the gene p27, which is known to control how cells grow. Patients with the -838AA genotype (17% of the patients) were 2.5 times more likely to have a successful graft over patients with either of the more common -838AC or -838CC genotypes. This result remained significant even when controlling for age, gender, diabetes and other clinical factors known to influence surgical outcomes. The study was funded partially by the National Heart, Lung and Blood Institute and Vascular Cures.

About PAD

Peripheral artery disease (PAD) is a build-up of plaque in the arteries of the leg and is a rapidly growing problem. PAD can cause significant pain and disability and affects more than 8 million Americans, requiring hundreds of thousands of surgeries and leading to over 80,000 amputations each year. The treatments used today to improve blood flow in patients with PAD are bypass surgery, angioplasty and stents. While often successful initially, these interventions frequently need to be repeated due to abnormal scar formation that causes re-narrowing of the artery or graft. The failure rates of angioplasty and stents are as high as 50 percent within one to two years, and half of all bypass procedures fail within five years.

About the Vascular Cures Research Network

The Vascular Cures Research Network is a national research consortium of up to 12 world-class medical institutions. Members of this collaborative team share information and results in order to substantially accelerate the development of new drugs, technologies and predictive tools to improve treatments for vascular disease.

Advances in genomics are putting the dream of individualized medicine within reach, identifying genetic profiles and biomarkers that predict disease or response to treatment. These discoveries rely on specialized analyses of tissue from large numbers of patients, maintained in a “biobank.” Vascular Cures is building the first national vascular biobank of blood and tissues from thousands of patients. The Vascular Cures Research Network and biobank will be a resource for researchers throughout the world for decades to come.

About Vascular Cures

A leader in vascular research, Vascular Cures invests in the development of breakthrough treatments to prevent disability and death from vascular disease. As an entrepreneurial nonprofit, Vascular Cures specifically designs its programs to speed the process of getting results to patients. Research by our network of leading vascular surgeon-scientists is advancing the development of powerful new ways to predict, treat and prevent vascular disease.