Compared to Intermittant Claudication Critical Limb Ischemia Is Associated with Elevated Levels of Cytokines

Area of Science:

• Vascular Biology
• Immunology
• Biomarkers

Background:

• Critical limb ischemia (CLI) represents the advanced stage of peripheral artery disease (PAD).
• CLI is associated with a significantly poorer clinical prognosis compared to intermittent claudication (IC).
• The underlying mechanisms contributing to CLI's poor outcomes, particularly the role of systemic inflammation, require further elucidation.

Purpose of the Study:

• To compare the circulating cytokine profiles of patients with CLI versus IC.
• To identify specific cytokines associated with CLI and their potential role in disease severity and outcome.

Main Methods:

• A cohort of 226 peripheral artery disease (PAD) patients undergoing invasive treatment for IC or CLI was analyzed.
• Circulating levels of 48 cytokines were measured in all participants.
• Multivariable linear regression models were used to assess associations between CLI and cytokine levels, adjusting for baseline differences.

Main Results:

• CLI patients, compared to IC patients, were older and had higher rates of chronic kidney disease and diabetes.
• CLI was independently associated with significantly elevated levels of numerous cytokines, including IL-1β, IL-6, IL-10, IFN-γ, GM-CSF, G-CSF, and VEGF.
• The cytokine profile in CLI patients resembled that seen in severe systemic conditions like sepsis or cancer.

Conclusions:

• Critical limb ischemia (CLI) is characterized by a distinct systemic inflammatory profile, evidenced by elevated circulating cytokines.
• This heightened systemic inflammation in CLI may contribute to the poor clinical outcomes observed in these patients.
• The findings suggest CLI is more than a localized vascular issue, but a systemic inflammatory condition.