Surreal illustration of a leg symbolizing PAD with DNA and a blood drop representing GDF15.

Could This Blood Test Save Your Limbs? The Promising Future of PAD Detection

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"New research highlights GDF15 as a potential game-changer in identifying and managing Peripheral Artery Disease, offering hope for early intervention and reduced amputation risk."

Peripheral Artery Disease (PAD) is a widespread manifestation of atherosclerosis, affecting millions globally. Despite advancements in healthcare, PAD continues to pose significant risks, including major amputation and mortality. Early detection and intervention are crucial to improving outcomes for individuals at risk.

A groundbreaking study published in the Journal of the American Heart Association sheds light on a promising biomarker, Growth Differentiation Factor 15 (GDF15), and its association with major amputation and mortality in PAD patients. This research suggests that GDF15 could be a valuable tool in identifying high-risk individuals and guiding treatment strategies.

GDF15 is a member of the transforming growth factor family, involved in processes like apoptosis and inflammation. Elevated levels of GDF15 may indicate increased cellular stress and damage, making it a potential marker for adverse clinical outcomes in various cardiovascular conditions, including PAD.

GDF15: A New Hope for PAD Management?

Surreal illustration of a leg symbolizing PAD with DNA and a blood drop representing GDF15.

The study, led by Judith J. De Haan and colleagues, involved analyzing data from two independent patient cohorts: the JUVENTAS trial and the Athero-Express Biobank. These cohorts included patients with critical limb ischemia and clinically manifest PAD. Researchers measured circulating GDF15 levels in these patients and correlated them with major adverse events, such as major amputation and all-cause mortality.

The results were compelling. Kaplan-Meier curves demonstrated that high levels of GDF15 were significantly associated with an increased risk of major events in both cohorts. This association remained significant even after adjusting for common confounders, suggesting that GDF15 provides independent prognostic information.

In the JUVENTAS trial, patients with the highest GDF15 levels had a four times greater risk of major events compared to those with the lowest levels.
Similarly, in the Athero-Express Biobank, high GDF15 levels were associated with a threefold increase in major event risk.
Interestingly, in the JUVENTAS trial, the association between GDF15 and major events was more pronounced in women, highlighting potential sex-based differences in PAD risk assessment.

These findings suggest that GDF15 could serve as an additive marker to improve the identification of patients at high risk of amputation or death, allowing for more informed treatment decisions and potentially better patient outcomes. The research indicates that incorporating GDF15 levels into risk assessment models could refine the prediction of adverse events in PAD patients beyond traditional risk factors.

The Future of PAD Diagnosis

The study's findings are promising, suggesting that GDF15 could be a valuable addition to the clinical toolkit for managing PAD. By identifying patients at higher risk, clinicians can tailor treatment strategies, potentially preventing major amputations and improving overall survival rates. Further research is needed to fully validate GDF15's clinical utility and to determine how best to integrate it into existing risk assessment algorithms. The potential benefits, however, are significant, offering hope for improved outcomes and a better quality of life for individuals living with PAD.

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This article is based on research published under:

DOI-LINK: 10.1161/jaha.117.006225, Alternate LINK

Title: Growth Differentiation Factor 15 Is Associated With Major Amputation And Mortality In Patients With Peripheral Artery Disease

Subject: Cardiology and Cardiovascular Medicine

Journal: Journal of the American Heart Association

Publisher: Ovid Technologies (Wolters Kluwer Health)

Authors: Judith J. De Haan, Saskia Haitjema, Hester M. Den Ruijter, Gerard Pasterkamp, Gert J. De Borst, Martin Teraa, Marianne C. Verhaar, Hendrik Gremmels, Saskia C. A. De Jager

Published: 2017-09-22

Everything You Need To Know

What is Peripheral Artery Disease (PAD), and why is early detection so important?

Peripheral Artery Disease (PAD) is a widespread manifestation of atherosclerosis, a condition where arteries become narrowed due to plaque buildup. Early detection is crucial because PAD can lead to severe complications, including major amputation and even mortality. Early intervention can help manage the disease, slow its progression, and improve outcomes for individuals at risk, potentially preventing these severe outcomes.

How does the blood test measuring GDF15 help in managing Peripheral Artery Disease (PAD)?

The blood test measuring Growth Differentiation Factor 15 (GDF15) is a potential game-changer in managing Peripheral Artery Disease (PAD). Elevated levels of GDF15, a member of the transforming growth factor family, may indicate increased cellular stress and damage, making it a potential marker for adverse clinical outcomes. By measuring GDF15 levels, clinicians can identify patients at a higher risk of major adverse events like amputation or death, allowing for more informed and timely treatment decisions.

What role did the JUVENTAS trial and the Athero-Express Biobank play in the study of GDF15 and PAD?

The JUVENTAS trial and the Athero-Express Biobank were crucial in studying the relationship between GDF15 and Peripheral Artery Disease (PAD). Researchers analyzed data from these two independent patient cohorts, which included patients with critical limb ischemia and clinically manifest PAD. By measuring circulating GDF15 levels in these patients and correlating them with major adverse events like amputation and all-cause mortality, researchers were able to establish a strong association between high GDF15 levels and increased risk. These cohorts helped validate the potential of GDF15 as a prognostic marker.

What were the key findings regarding the association between GDF15 levels and major events in PAD patients?

The research demonstrated that high levels of GDF15 were significantly associated with an increased risk of major adverse events in Peripheral Artery Disease (PAD) patients. Specifically, in the JUVENTAS trial, patients with the highest GDF15 levels had a four times greater risk of major events. Similarly, in the Athero-Express Biobank, high GDF15 levels were associated with a threefold increase in major event risk. This association remained significant even after adjusting for common confounders, indicating that GDF15 provides independent prognostic information, thus identifying high-risk individuals.

How could the integration of GDF15 into risk assessment models improve the management of PAD?

Integrating GDF15 levels into risk assessment models could significantly improve the management of Peripheral Artery Disease (PAD). By identifying patients at higher risk of amputation or death, clinicians can tailor treatment strategies more effectively. This might involve more aggressive interventions, such as lifestyle modifications, medications, or more invasive procedures, to prevent adverse events. Incorporating GDF15 could refine the prediction of adverse events beyond traditional risk factors, leading to better patient outcomes, potentially preventing major amputations, and improving overall survival rates for individuals living with PAD.