Related Experiment Video
Updated: Jul 26, 2025
Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia
Published on: September 22, 2020
Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening
Elisabetta Nardella1, Federico Biscetti2,3, Maria Margherita Rando1
1Cardiovascular Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, Roma, 00168, Italy.
Insights
Biomarkers like IL-6 and CRP predict adverse cardiac and limb events after lower-extremity revascularization in diabetic patients with chronic limb threatening ischemia. Identifying high-risk patients early can improve outcomes.
Area of Science:
- Vascular Surgery
- Cardiology
- Diabetology
- Biomarker Research
Background:
- Diabetic patients with chronic limb threatening ischemia (CLTI) often require lower-extremity endovascular revascularization (LER).
- Post-LER complications include major adverse cardiac events (MACE) and major adverse limb events (MALE).
- Cytokines play a role in atherosclerosis, suggesting potential biomarkers for MACE and MALE risk.
Purpose of the Study:
- To investigate the relationship between baseline biomarker levels and MACE/MALE after LER in diabetic CLTI patients.
- To assess the predictive value of a panel of inflammatory biomarkers for vascular outcomes post-LER.
- To determine if biomarkers improve risk prediction beyond traditional factors.
Main Methods:
- Prospective non-randomized study of 264 diabetic CLTI patients undergoing LER.
- Baseline serum biomarker levels (IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG, Sortilin, Omentin-1) were measured.
- MACE and MALE incidence were tracked for 12 months post-revascularization.
Main Results:
- Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG, and Sortilin levels were associated with increased MACE and MALE.
- Low Omentin-1 levels were inversely related to MACE and MALE.
- Biomarker inclusion significantly improved risk prediction models for incident events.
Conclusions:
- Baseline levels of specific inflammatory biomarkers predict adverse vascular outcomes in diabetic CLTI patients post-LER.
- This biomarker panel can help identify patients at higher risk for MACE, MALE, and procedure failure.
- Inflammatory state assessment may guide clinical management to prevent post-LER complications.
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.
Related Concept Videos
01:21Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:27Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
01:27Peripheral Artery Disease III: Interprofessional Care
01:30Coronary Artery Disease I: Introduction