title: Does inflammation predispose to recurrent vascular events after recent transient ischaemic attack and minor stroke? The North West of England transient ischaemic attack and minor stroke (NORTHSTAR) study.
abstract: OBJECTIVE
  Inflammation is implicated in the pathogenesis and outcome of ischaemic injury. Poststroke inflammation is associated with outcome but it remains unclear whether such inflammation precedes or results from ischaemic injury. We hypothesised that inflammatory markers are associated with an increased risk of recurrent vascular events soon after transient ischaemic attack and minor stroke.
  
  
  METHODS
  This was a multicentre, prospective, nested case-control study. Plasma concentrations of C-reactive protein, interleukin-6, interleukin-1-receptor antagonist and fibrinogen, leucocyte counts, erythrocyte sedimentation rate and inflammatory gene allele frequencies were analysed in 711 patients with recent transient ischaemic attack or minor stroke. Cases were defined by the incidence of one or more recurrent vascular events during the three-month follow-up. Association of inflammatory markers with case-status was determined using conditional logistic regression.
  
  
  RESULTS
  Plasma concentrations of C-reactive protein, interleukin-1-receptor antagonist and interleukin-6 were not associated with case-status. In secondary analyses, only erythrocyte sedimentation rate was significantly associated with case-status (odds ratio 1·39, 95% confidence interval 1·03-1·85; P=0·03), but this effect did not persist after adjustment for smoking and past history of transient ischaemic attack or stroke. Single nucleotide polymorphisms in four inflammatory genes (interleukin-6, fibrinogen, P-selectin and vascular cell adhesion molecule-1) were nominally associated with case-status.
  
  
  CONCLUSIONS
  Circulating inflammatory markers were not associated with recurrent vascular events. Nominally significant associations between genetic markers and case-status will require replication. These data provide little evidence for an inflammatory state predisposing to stroke and other vascular events in a susceptible population.
authors.affiliation: Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK. johann.selvarajah@manchester.ac.uk
authors.forename: Johann R
authors.initials: JR
authors.lastname: Selvarajah
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Sharon
authors.initials: S
authors.lastname: Hulme
authors.forename: Rachel
authors.initials: R
authors.lastname: Georgiou
authors.forename: Charles
authors.initials: C
authors.lastname: Sherrington
authors.forename: John
authors.initials: J
authors.lastname: Staniland
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Illingworth
authors.forename: Francine
authors.initials: F
authors.lastname: Jury
authors.forename: Antony
authors.initials: A
authors.lastname: Payton
authors.forename: William E
authors.initials: WE
authors.lastname: Ollier
authors.forename: Andy
authors.initials: A
authors.lastname: Vail
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hopkins
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Tyrrell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D016001:Confidence Intervals; D004739:England / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D018401:Sample Size; D012959:Socioeconomic Factors; D020521:Stroke / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers