Abstract
Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GROα, HGF, SCF, SCGFβ, SDF1α, TRAIL, IL-6, IL-8, FGFβ, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFα, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n = 108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GROα and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n = 146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15–1.70, p = 0.0007) and 1.48 (95% CI 1.16–1.87, p = 0.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models.
Highlights
Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality
Levels of GROα, Hepatocyte Growth Factor (HGF), Stem Cell Factor (SCF), IL-6, IL-8, Granulocyte-colony stimulating factor (G-CSF), Induced Protein 10 (IP-10), Vascular Endothelial Growth Factor (VEGF), soluble Intercellular Cell-Adhesion Molecule 1 (sICAM)-1, soluble Vascular Cell Adhesion Molecule 1 (sVCAM)-1 and TM were higher in SLI patients compared to controls
In the present study we show that elevated serum levels of the inflammatory biomarkers IL-6 and IP-10 are independently associated with major clinical events in SLI patients
Summary
Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. We investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models. Circulating biomarkers that have been associated with the development of PAD and SLI, including sICAM-18, sVCAM-19, CRP10 and IL-611 reflect endothelial damage, oxidative stress, angiogenesis and inflammation[9,12]. We use baseline samples of no-option SLI patients included in the JUVENTAS cohort[16] to identify predictors for major amputation or death. We investigate which of these processes is most closely associated with major outcomes and predicts events independently of established risk factors. The results are subsequently validated in the remaining JUVENTAS cohort as well as in an independent cohort of patients from the AtheroExpress study[17] including milder forms of PAD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
