title: Association between interleukin-6 levels and first-ever cerebrovascular events in patients with vascular risk factors.
abstract: OBJECTIVE
  The objective of this study was to examine the association of inflammatory markers with risk of first-ever cerebrovascular events (CVEs), while simultaneously evaluating subclinical vascular disease.
  
  
  RESULTS
  We enrolled 464 outpatients who had vascular risk factors without any preexisting cardiovascular disease. We examined the presence of silent lacunar infarction (SLI) by magnetic resonance imaging; carotid intima-media thickness by ultrasound; and measured high-sensitivity C-reactive protein, interleukin (IL)-6, and IL-18 at baseline, and assessed their associations with CVEs using Cox proportional hazards models of 4.8±2.6 years follow-up. We further calculated measures of reclassification and discrimination. In age- and sex-adjusted analysis, IL-6, but neither high-sensitivity C-reactive protein nor IL-18, was associated with CVEs. The association remained significant after adjustment for conventional risk factors, intima-media thickness, and SLI (hazard ratios: 1.80, per 1-SD increase in log IL-6, P=0.03). Compared with the patients with below median IL-6 without SLI, those with above median IL-6 and SLI had a higher risk of CVEs (hazard ratios: 4.14, P=0.0014). The combination of IL-6 and SLI resulted in the net reclassification improvement of 14.3% (P=0.04), and the integrated discrimination improvement gain of 2.1% (P=0.05).
  
  
  CONCLUSIONS
  IL-6 levels were independently associated with CVEs and could improve reclassification in those with SLI.
authors.affiliation: Department of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Miwa
authors.forename: Makiko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Shuhei
authors.initials: S
authors.lastname: Okazaki
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Furukado
authors.forename: Manabu
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D059168:Carotid Intima-Media Thickness; D002533:Cerebral Angiography / Q000379:methods; D002561:Cerebrovascular Disorders / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D016009:Chi-Square Distribution; D016002:Discriminant Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D059409:Stroke, Lacunar / Q000453:epidemiology / Q000276:immunology; D013997:Time Factors
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D020382:Interleukin-18; D015850:Interleukin-6; D002097:C-Reactive Protein