Abstract 20864: The Inflammatory Biomarkers IL-6 and IP-10 Predict Amputation and Mortality in Patients With Severe Limb Ischemia
Background: Patients with Severe Limb Ischemia (SLI) have a high risk of amputations and mortality. In this study we investigate whether levels of inflammatory plasma cytokines, angiogenic growth factors or endothelial damage markers are associated with major outcomes in SLI.
Methods and Results: Data were collected from a randomized controlled trial cohort investigating cell therapy for SLI (the JUVENTAS study). The primary outcome was major events, defined as amputation or death, at 1 year. In a discovery cohort of 108 patients, a panel of cytokines consisting of GROa, HGF, LIF, SCF, SCGFb, SDF1a, TRAIL, IL-6, IL-8, FGFb, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFa, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum. 34 patients had experienced an event at 1 year after inclusion. In multivariate analysis a clinical prediction model consisting of IL-6, IP-10, Ankle-Brachial Index and Hemoglobin was found to best predict outcomes, with a C-statistic of 86.6% (figure 1A). The model was independently validated in a second cohort of a further 52 patients, where it displayed similar prediction performance (C-statistic 80.5%). Model scores were additionally evaluated in survival analysis (median follow-up 3 years): patients in the highest tertile had a Hazard Rate of 13.3 (95% CI 5.4 - 32.7, p = 1.65 x 10-8) for major events compared to the lowest tertile of model scores (figure 1B).
Conclusion: We identified two inflammatory biomarkers, IL-6 and IP-10 that predict major events, in a cohort of patients with SLI. In longitudinal follow-up levels of IL-6 and IP-10 were strongly related to disease-outcome, consistent with a role for inflammation in disease progression.
Author Disclosures: H. Gremmels: None. M. Teraa: None. J.O. Fledderus: None. B.W. van Balkom: None. M.C. Verhaar: None.
- © 2016 by American Heart Association, Inc.