Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study

BMC Neurol. 2019 Jul 3;19(1):148. doi: 10.1186/s12883-019-1375-6.

Abstract

Background: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome.

Methods: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed.

Results: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time.

Conclusions: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset.

Trial registration: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

Keywords: Biomarkers; Ischemic stroke; Mortality; Outcome.

Publication types

  • Multicenter Study

MeSH terms

  • Acute-Phase Proteins
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / complications
  • Biomarkers / blood
  • Brain Ischemia / blood
  • Brain Ischemia / complications
  • Brain Ischemia / immunology*
  • Brain Ischemia / mortality
  • Carrier Proteins / blood
  • Diabetes Mellitus
  • Female
  • Germany
  • HLA-DR Antigens / blood*
  • Humans
  • Immune Tolerance
  • Inflammation / complications
  • Interleukin-10 / blood
  • Interleukin-6 / blood*
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Pneumonia / etiology*
  • Pneumonia / mortality
  • Prospective Studies
  • Spain
  • Stroke / blood
  • Stroke / complications
  • Stroke / immunology*
  • Stroke / mortality
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Carrier Proteins
  • HLA-DR Antigens
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide-binding protein
  • Interleukin-10

Associated data

  • ClinicalTrials.gov/NCT01079728