Detecting Risk of Peripheral Arterial Disease

by Adrienne Mueller, PhD
March 21, 2022    

Peripheral artery disease (PAD) is a condition afflicting over 200 million individuals world-wide. It occurs when arteries in your arms and legs narrow to the point that they restrict blood flow. Symptoms can include numbness, weakness, and pain in the affected limbs, and severe cases may need to be treated with surgery. Individuals with PAD also have a two- to six-fold higher risk of major adverse cardiovascular events such as heart attacks. In the US, PAD generates an estimated annual health care cost of approximately $21 billion.

Increasing polygenic risk scores tracked with increased prevalence of peripheral artery disease (PAD).

PAD is a complex disorder with many contributing risk factors, including age, diabetes, smoking, and genetics. However specific genes that contribute to PAD have been difficult to identify; partly because the effects of individual genes can be small and a lot of data is needed to identify the combined effect of many genes on increasing someone’s risk of developing PAD. A recent large-scale genome-wide association study used data from over 30,000 individuals with PAD and identified numerous new genetic loci that are specifically associated with risk of PAD.

The next question is – how well does knowing about those genes help us predict whether a person will develop PAD. To address this question, a team of researchers from Stanford Vascular Surgery and Cardiovascular Medicine used the findings from the genome-wide association study to develop a model of an individual’s risk of developing PAD. This model generates a polygenic risk score for PAD. The researchers then tested their model on the genomic data from over 487,000 individuals from the UK Biobank. Their findings, led by first author Fudi Wang, PhD, and senior author Elsie Ross, MD, were recently published in Vascular Medicine.

Wang et al showed that individuals with the top 10% of highest polygenic risk scores had a 3-fold higher likelihood of having PAD than the 10% with the lowest scores. Additionally, the score helped predict increased risk of other cardiovascular disorders such as coronary artery disease, congestive heart failure, and cerebrovascular disease. Use of the polygenic risk score significantly improved the ability to detect individuals’ risk of having PAD, and in the future it will be a valuable tool to improve early identification of this prevalent but undiagnosed disease.

Additional Stanford Cardiovascular Institute-affiliated authors who contributed to this study include Ilies Ghanzouri, Nicholas J Leeper, and Philip S Tsao.

Dr. Fudi Wang

Dr. Elsie Ross