Impact of inflammation on chronic limb-threatening ischaemia

INTRODUCTION: Peripheral arterial disease (PAD) affects more than 202 million people worldwide, 1.3% of which with chronic limb-threatening ischaemia (CLTI). PAD is associated with an elevated mortality and morbidity. However, the evolution from claudication or from asymptomatic PAD to CLTI is not completely understood and cardiovascular risk factors are unable to fully explain it. The aim of this opportunistic review is to understand the role of inflammation in the evolution to CLTI and to analyse if inflammation can increase the mortality risk. METHODS: A systematic search of the PubMed database was performed with the keywords and medical subject heading (MesH): “inflammation”, “cytokine”, “prognosis”, “death”, “mortality”, “CLTI” and “CLI”. Of 146 papers, 8 articles and 1622 patients were included RESULTS: We verified that inflammation is important for the initiation and progression of PAD. There are several candidate inflammatory triggers, including the cardiovascular risk factors (age, nicotine abuse, diabetes mellitus, hypercholesterolemia). However, these traditional risk factors, fail to explain the variable nature of disease progression between individuals and the pro-inflammatory polymorphisms could be a key element. Several studies also proved that patients with CLTI have a marked elevated level of cytokines. The increase inflammatory burden in patients with PAD, particularly with CLTI could explain the increased inflammation and may help to explain why the prevalence of clinically manifested coronary artery disease in PAD is much higher than the prevalence of PAD in coronary artery disease patients. CONCLUSION: Anti-inflammatory therapy and revascularization can avoid the systemic consequences of inflammation in patient with CLTI and should be timely implemented.