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Published on: September 22, 2020
Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia
Alexandra Ioana Popescu1, Andreea Luciana Rata2, Sorin Barac3
1Pharmacology Department, Doctoral School, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania.
Insights
Inflammation markers are elevated in chronic limb-threatening ischemia (CLTI), indicating a link between inflammation, diabetes, and adverse cardiovascular or limb events in CLTI patients.
Area of Science:
- Vascular Medicine
- Biomarker Research
- Peripheral Arterial Disease
Background:
- Chronic limb-threatening ischemia (CLTI) is an advanced stage of peripheral arterial disease.
- CLTI is characterized by ischemic rest pain, non-healing ulcers, or gangrene.
- Inflammation and endothelial dysfunction are key contributors to CLTI pathogenesis.
Purpose of the Study:
- To review biological markers associated with CLTI.
- To explore the relationship between these markers and adverse outcomes in CLTI patients.
Main Methods:
- A narrative review adhering to PRISMA guidelines.
- Searched Web of Science, Medline, and EMBASE databases.
- Included 22 studies assessing CLTI and related biological markers.
Main Results:
- Identified numerous markers (e.g., C-reactive protein, D-dimers, IL-6, TNF-α, ICAM-1, VCAM-1, NLR) positively associated with advanced CLTI.
- These markers correlated with major limb or major cardiovascular events in CLTI patients.
- Elevated marker values were particularly pronounced in CLTI patients with diabetes mellitus.
Conclusions:
- Increased levels of various biological markers are observed in CLTI patients.
- Diabetes mellitus exacerbates the association between CLTI and adverse cardiovascular or limb events.
- Further research is needed to validate these markers for diagnosis/prognosis and develop targeted therapies for inflammation and endothelial dysfunction in CLTI.
Background:
Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI.
Methods:
A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it.
Results:
We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients.
Conclusions:
All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.
