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Cardiovascular Diabetology
Published in:

Open Access 01-12-2023 | Biomarkers | Research

Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study

Authors: Elisabetta Nardella, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Published in: Cardiovascular Diabetology | Issue 1/2023

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Abstract

Background

Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI.

Methods

In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes’ incidence was evaluated after 1, 3, 6 and 12 months.

Results

During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events.

Conclusions

Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.
Appendix
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Metadata
Title
Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study
Authors
Elisabetta Nardella
Federico Biscetti
Maria Margherita Rando
Andrea Leonardo Cecchini
Maria Anna Nicolazzi
Enrica Rossini
Flavia Angelini
Roberto Iezzi
Luis H. Eraso
Paul J. Dimuzio
Dario Pitocco
Massimo Massetti
Antonio Gasbarrini
Andrea Flex
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Biomarkers
Published in
Cardiovascular Diabetology / Issue 1/2023
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-023-01872-x

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