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

Juho Jalkanen,Mikael Maksimow,Maija Hollmén,Harri Hakovirta,Sirpa Jalkanen,Maria Cristina Vinci

doi:10.1371/journal.pone.0162353

Juho Jalkanen, Mikael Maksimow + Show 4 more

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https://doi.org/10.1371/journal.pone.0162353

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Journal: PloS one	Publication Date: Sep 9, 2016
Citations: 27	License type: CC BY 4.0

Affiliation: Turku University Hospital, University of Turku

Abstract

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) and associated with an extremely poor clinical outcome. In order to understand the possible role of circulating cytokines and poor outcome associated with CLI we compared the circulating cytokine profile of patients with CLI against patients with intermittent claudication (IC). The levels of 48 circulating cytokines were examined in 226 consecutive patients with peripheral artery disease (PAD) admitted for elective, non-urgent, invasive treatment of IC or CLI. The PAD patient cohort was evenly distributed between subjects with IC (46.5%) and CLI (53.5%). As accustomed in PAD, CLI was associated with higher age, chronic kidney disease and diabetes when compared to IC (P < 0.01 for all). In multivariable linear regression modeling taking into account the baseline differences between IC and CLI groups CLI was independently associated with elevated levels of a large number of cytokines: IL-1β, IL-1ra, IL-2Rα, IL-4, IL-6, IL-10, IFN-γ, GM-CSF, G-CSF (P < 0.01 for all), and IL-2, IL-7, IL-12, IL-13, IL-17, bFGF, VEGF, SCGF-β (P < 0.05 for all). The current findings indicate that CLI is associated with a circulating cytokine profile, which resembles serious medical conditions such as severe pancreatitis, sepsis, or even cancer. Compared to IC, CLI is a systemic inflammatory condition, which may explain the extremely poor outcome associated with it.

Highlights

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) in which atherosclerotic occlusions of the lower limbs arteries cause insufficient flow to maintain viable peripheral tissue
To further understand the nature of CLI and possible inflammatory activity associated with it, we examined the circulating levels of 48 different cytokines, chemokines and growth factors in a prospectively gathered cohort of patients with diagnosed and symptomatic PAD and compared patients with intermittent claudication (IC) and CLI against each other adjusting for age, co-morbidities, risk factors, and concomitant medication
Upon admission limb ischemia was scored in all patients according to ankle-brachial index (ABI), symptoms and clinical manifestations according to the Rutherford classifications

Summary

Introduction

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) in which atherosclerotic occlusions of the lower limbs arteries cause insufficient flow to maintain viable peripheral tissue. Clinical manifestations include rest pain, non-healing ulcers, and gangrene. If revascularization is not performed the condition is associated with an extremely high risk of limb loss [1,2]. Even after successful revascularization this patient group is characterized with severe cardiovascular morbidity and increased mortality [3,4,5]. Despite major efforts PAD remains an unrecognized emerging health crisis [2,6,7]. Over 200 million people suffer from PAD worldwide, and its incidence and burden of death is PLOS ONE | DOI:10.1371/journal.pone.0162353. Over 200 million people suffer from PAD worldwide, and its incidence and burden of death is PLOS ONE | DOI:10.1371/journal.pone.0162353 September 9, 2016

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