Abstract 25: Critical Limb Ischemia Progression is Associated with an Inflammatory Profile

Abstract

Background: Patients with Critical Limb Ischemia (CLI) have a high risk of amputations and mortality. We hypothesize that inflammation is involved in atherosclerotic disease progression. In this study we investigate whether levels of plasma cytokines are associated with disease progression in CLI. Methods: Data were collected from a randomized controlled trial cohort investigating cell therapy for CLI (the JUVENTAS study) from 2006 to 2012. The primary outcome measures were major amputation and mortality at 6 months; secondary outcomes included Ankle/Brachial Index (ABI) and Transcutaneous O2 Pressure. Plasma was collected at inclusion in the study and 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 and VEGF was measured and evaluated for predictive power. Results: Data on 108 patients was collected with a follow-up of 6 months. Patients who underwent a major outcome had significantly higher levels of IL-6, IL-8 and GROa (p=0.0004, 0.006 and 0.009 resp.). Univariate Kaplan-Meier analysis showed that amputation-free survival was 94.4% in the lowest tertile, 74% in the middle tertile and 64% in the highest tertile of plasma IL-6 levels (p=0.009, Fig A). Adjustment for potential confounders in multivariate Cox proportional hazards models showed that IL-6 remained independent predictor of major outcome. The ROC of a model using Il-6 as single predictor for major outcomes is 0.73 (Fig. B) Conclusion: Plasma levels of inflammatory cytokines, in particular IL-6 are associated with disease progression in CLI and can serve as an independent predictor of amputation-free survival.