title: Inflammatory Markers and Outcomes After Lacunar Stroke: Levels of Inflammatory Markers in Treatment of Stroke Study.
abstract: OBJECTIVE
  We hypothesized that concentrations of interleukin 6 (IL-6), serum amyloid A, tumor necrosis factor-α receptor 1, CD40 ligand, and monocyte chemoattractant protein 1 would predict recurrent ischemic stroke and major vascular events after recent lacunar stroke.
  
  
  METHODS
  Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) study, a Phase III trial in patients with recent lacunar stroke. Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for recurrence risks.
  
  
  RESULTS
  Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), there were 115 major vascular events (stroke, myocardial infarction, and vascular death). The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-α receptor 1 (adjusted HR per SD, 1.21; 95% CI, 1.05-1.41; P=0.01) and IL-6 (adjusted HR per SD, 1.10; 95% CI, 1.02-1.19; P=0.008). Compared with the bottom quartile (tumor necrosis factor-α receptor 1 <2.24 ng/L), those in the top quartile of tumor necrosis factor-α receptor 1 (>3.63 ng/L) were at twice the risk of major vascular events after adjusting for demographics (partially adjusted HR, 1.98; 95% CI, 1.11-3.52), though the effect attenuated after adjusting for other risk factors and statin use (adjusted HR, 1.68; 95% CI, 0.93-3.04). Serum amyloid A, CD40 ligand, and monocyte chemoattractant protein 1 were not associated with prognosis.
  
  
  CONCLUSIONS
  Among recent lacunar stroke patients, IL-6 and TNF receptor concentrations predict risk of recurrent vascular events, and they are associated with the effect of antiplatelet therapies.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.). akb2188@cumc.columbia.edu.
authors.forename: Amelia K
authors.initials: AK
authors.lastname: Boehme
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.).
authors.forename: Leslie A
authors.initials: LA
authors.lastname: McClure
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.).
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Luna
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.).
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Del Brutto
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.).
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Benavente
authors.affiliation: From the Department of Neurology, College of Physicians and Surgeons (A.K.B., J.M.L., M.S.V.E.) and Department of Epidemiology, Mailman School of Public Health (A.K.B., M.S.V.E.), Columbia University, New York; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); Department of Biostatistics, School of Public Health, University of Alabama at Birmingham (Y.Z.); Department of Neurological Sciences, Universidad de Especialidades Espíritu Santo, Guayaquil, Ecuador (O.H.D.B.); and Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.).
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012307:Risk Factors; D059409:Stroke, Lacunar / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D047888:Receptors, Tumor Necrosis Factor, Type I
keywords: inflammation; interleukin 6; lacunar stroke; prognosis; stroke