title: Association between inflammatory biomarkers and progression of intracranial large artery stenosis after ischemic stroke.
abstract: BACKGROUND
  Proinflammatory state has been implicated as a pathogenetic mechanism in the progression of intracranial large artery atherosclerosis (ILA). High levels of inflammatory biomarkers in healthy populations and in patients with acute stroke or acute coronary syndrome are known to be associated with subsequent stroke events. This study investigated the relationship between circulating biomarkers measured early after stroke onset and future ILA progression.
  
  
  METHODS
  In 48 patients with acute ischemic stroke, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2 and MMP-9 were measured within 48 hours after onset. Baseline severity and ILA progression were assessed by serial magnetic resonance angiography (MRA). The median follow-up period for MRA was 3.1 years. Hazard ratio (HR) was calculated using the Cox proportional hazard model adjusted for traditional risk factors, and accuracy of predicted ILA progression was analyzed by receiver operating characteristic (ROC) curve analysis.
  
  
  RESULTS
  ILA progression was observed in 6 of 48 patients (12.5%). After adjusting for age, sex, and presence of hypertension, baseline ILA severity score (HR 2.814; 95% confidence interval [CI] 1.172-6.754) and IL-6 (HR 1.215; 95% CI 1.002-1.473) were significantly associated with ILA progression. Area under the ROC curve (AUC) for prediction of ILA progression by traditional risks, baseline ILA severity score and IL-6, was 0.647. When IL-6 was removed from this model, AUC remained at 0.631.
  
  
  CONCLUSIONS
  In addition to traditional risk factors and baseline radiologic findings, circulating levels of IL-6 measured soon after stroke onset are associated with future ILA progression.
authors: Department of Internal Medicine, Division of Neurology, St. Marianna University School of Medicine, Kanagawa, Japan. shinnai@marianna-u.ac.jp
authors: Kanako
authors: K
authors: Shimizu
authors: Kana
authors: K
authors: Shimomura
authors: Yoshiaki
authors: Y
authors: Tokuyama
authors: Kenzo
authors: K
authors: Sakurai
authors: Kenji
authors: K
authors: Isahaya
authors: Satoshi
authors: S
authors: Takaishi
authors: Bunta
authors: B
authors: Kato
authors: Noriko
authors: N
authors: Usuki
authors: Takahiro
authors: T
authors: Shimizu
authors: Koji
authors: K
authors: Yamada
authors: Yasuhiro
authors: Y
authors: Hasegawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D002533:Cerebral Angiography / Q000379:methods; D002536:Cerebral Arteries / Q000473:pathology*; D016009:Chi-Square Distribution; D003251:Constriction, Pathologic; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6