Reversion of the inflammatory markers in patients with chronic limb threatening ischaemia

Introduction Peripheral arterial disease (PAD) affects over 202 million individuals worldwide, with 1.3% suffering from chronic limb-threatening ischaemia (CLTI). Atherosclerosis, characterized by intense inflammation, is the primary cause of PAD. Inflammation is linked to higher mortality rates, especially in CLTI patients. This study aims to compare the evolution of inflammatory markers between claudication and CLTI patients over three, six, and twelve months. Methods A prospective, single-center observational study was conducted from January 2018 to July 2022. A PAD cohort was observed at admission and at three, six, and twelve months, with data on clinical, analytical, and inflammatory markers collected. The analyzed markers included positive acute phase proteins (C-reactive protein - CRP and fibrinogen) and negative acute phase proteins (albumin, total cholesterol, and high-density lipoprotein - HDL). Results The study involved 119 subjects (mean age: 67.58 ± 9.60 years; 79.80% males), with 65 patients having claudication and 54 with CLTI. At admission, CLTI patients exhibited significantly higher serum levels of CRP and fibrinogen (positive acute phase proteins) and lower levels of albumin, total cholesterol, and HDL (negative acute phase proteins) compared to claudication patients. Three months after CLTI resolution, negative acute phase proteins increased, and positive acute phase proteins decreased. However, no significant changes in inflammatory proteins were observed in patients with claudication over time. Conclusion CLTI patients demonstrate an inflammatory state, which may have deleterious consequences and be partially reversible after the resolution of the ischemic process. Recognizing the potential for reversibility through revascularization/amputation underscores the significance of timely intervention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Portuguese Society of Vascular Surgery. This work was developed under the scope of project NORTE-01-0145-FEDER- 000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER), and by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was obtained from the local Hospital, with the protocol number 75/2017. The email from the hsopital in question is geral{at}hospitaldeguimaraes.min-saude.pt. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes In case data is requested, it will be provided.