TY - JOUR
T1 - A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia
AU - Gremmels, Hendrik
AU - Teraa, Martin
AU - de Jager, Saskia C.A.
AU - Pasterkamp, Gerard
AU - de Borst, Gert J.
AU - Verhaar, Marianne C.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069704732&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-47217-1
DO - 10.1038/s41598-019-47217-1
M3 - Article
C2 - 31341203
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 10740
ER -