Impact of inflammation on chronic limb-threatening ischaemia
DOI:
https://doi.org/10.48750/acv.487Keywords:
Inflammation, peripheral arterial disease, chronic limb-threatening ischaemia, cytokinesAbstract
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.
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References
Brevetti G, Giugliano G, Brevetti L, Hiatt WR. Inflammation in Peripheral Artery Disease. Circulation 2010;122:1862–75. https://doi.org/10.1161/CIRCULATIONAHA.109.918417.
Simon F, Oberhuber A, Floros N, Düppers P, Schelzig H, Duran M. Pathophysiology of chronic limb ischemia. Gefässchirurgie 2018;23:13–8. https://doi.org/10.1007/s00772-018-0380-1.
Jalkanen J, Maksimow M, Hollmén M, Jalkanen S, Hakovirta H. Compared to Intermittant Claudication Critical Limb Ischemia Is Associated with Elevated Levels of Cytokines. PLOS ONE 2016;11:e0162353. https://doi.org/10.1371/journal.pone.0162353.
Aday AW, Matsushita K. Epidemiology of Peripheral Artery Disease and Polyvascular Disease. Circulation Research 2021;128:1818–32. https://doi.org/10.1161/CIRCRESAHA.121.318535.
Girn HRS, Orsi NM, Homer-Vanniasinkam S. An overview of cytokine interactions in atherosclerosis and implications for peripheral arterial disease. Vascular Medicine 2007;12:299–309. https://doi.org/10.1177/1358863X07083387.
Fiotti N, Giansante C, Ponte E, Delbello C, Calabrese S, Zacchi T, et al. Atherosclerosis and inflammation. Patterns of cytokine regulation in patients with peripheral arterial disease. Atherosclerosis 1999;145:51–60. https://doi.org/10.1016/S0021-9150(99)00013-1.
Wozniak K, Sleszycka J, Safianowska A, Wiechno W, Domagala-Kulawik J. Systemic inflammation in peripheral arterial disease with or without coexistent chronic obstructive pulmonary disease: Analysis of selected markers. Archives of Medical Science 2012;8:477–83. https://doi.org/10.5114/aoms.2012.29403.
Gremmels H, Teraa M, de Jager SCA, Pasterkamp G, de Borst GJ, Verhaar MC. A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia. Scientific Reports 2019;9:10740. https://doi.org/10.1038/s41598-019-47217-1.
Barani J, Nilsson J-Å, Mattiasson I, Lindblad B, Gottsäter A. Inflammatory mediators are associated with 1-year mortality in critical limb ischemia. Journal of Vascular Surgery 2005;42:75–80. https://doi.org/10.1016/j.jvs.2005.03.025.
Flex A, Gaetani E, Angelini F, Sabusco A, Chillà C, Straface G, et al. Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia. Journal of Internal Medicine 2007;262:124–30. https://doi.org/10.1111/j.1365-2796.2007.01791.x.
Pärsson H, Holmberg A, Siegbahn A, Bergqvist D. Activation of Coagulation and Fibrinolytic Systems in Patients with CLI is not Normalized after Surgical Revascularisation. European Journal of Vascular and Endovascular Surgery 2004;27:186–92. https://doi.org/10.1016/j.ejvs.2003.10.015.
Gary T, Belaj K, Hafner F, Eller P, Rief P, Hackl G, et al. Graz Critical Limb Ischemia Score. Medicine 2015;94:e1054. https://doi.org/10.1097/MD.0000000000001054.
Woodburn KR, Rumley A, Lowe GDO, Pollock JG. Fibrinogen and markers of fibrinolysis and endothelial damage following resolution of critical limb ischaemia. European Journal of Vascular and Endovascular Surgery 1995;10:272–8. https://doi.org/10.1016/S1078-5884(05)80042-5.
Komarov AL, Panchenko EP, Dobrovolsky AB, Karpov YA, Deev AD, Titaeva E v., et al. D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease. European Heart Journal 2002;23:1309–16. https://doi.org/10.1053/euhj.2001.3116.
