title: High-sensitivity C-reactive protein and interleukin-6-dominant inflammation and ischemic stroke risk: the northern Manhattan study.
abstract: OBJECTIVE
  Interleukin-6 (IL-6) is a proinflammatory cytokine with known autoregulatory feedback mechanisms. We hypothesized that elevated high-sensitivity C-reactive protein (hsCRP) relative to IL-6 confers an increased risk of ischemic stroke (IS), and low hsCRP relative to IL-6 a decreased risk, for individuals in the prospective, multiethnic, population-based Northern Manhattan Study (NOMAS).
  
  
  METHODS
  Serum hsCRP and IL-6 were measured in NOMAS participants at baseline. We created a trichotomized predictor based on the dominant biomarker in terms of quartiles: hsCRP-dominant, IL-6-dominant, and codominant groups. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for the association between inflammatory biomarker group status and risk of incident IS.
  
  
  RESULTS
  Of 3298 participants, both hsCRP and IL-6 were available in 1656 participants (mean follow-up, 7.8 years; 113 incident IS). The hsCRP-dominant group had increased risk of IS (adjusted hazard ratio, 2.62; 95% confidence interval, 1.56-4.41) and the IL-6-dominant group had decreased risk (adjusted hazard ratio, 0.38; 95% confidence interval, 0.18-0.82) when compared with the referent group, after adjusting for potential confounders. Model fit was improved using the inflammation-dominant construct, over either biomarker alone.
  
  
  CONCLUSIONS
  In this multiethnic cohort, when hsCRP-quartile was higher than IL-6 quartile, IS risk was increased, and conversely when IL-6 quartiles were elevated relative to hsCRP, IS risk was decreased. Construct validity requires confirmation in other cohorts.
authors.affiliation: From the Department of Epidemiology, Mailman School of Public Health, New York, NY (J.M.L., M.S.V.E.); Departments of Neurology (Y.P.M., M.S.V.E.) and Pathology (K.M.L., S.S.), Columbia University College of Physicians and Surgeons, New York, NY; Division of Biostatistics, Mailman School of Public Health, New York, NY (M.C.P., K.C.); Departments of Neurology, Epidemiology, and Human Genetics, Miller School of Medicine, University of Miami, FL (R.L.S.); and Gertrude H. Sergievsky Center, Columbia University, New York, NY (M.S.V.E.).
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Luna
authors.forename: Yeseon P
authors.initials: YP
authors.lastname: Moon
authors.forename: Khin M
authors.initials: KM
authors.lastname: Liu
authors.forename: Steven
authors.initials: S
authors.lastname: Spitalnik
authors.forename: Myunghee C
authors.initials: MC
authors.lastname: Paik
authors.forename: Keun
authors.initials: K
authors.lastname: Cheung
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: biomarkers; inflammation; ischemic stroke; prevention and control