title: Association Between Markers of Inflammation and Total Stroke by Hypertensive Status Among Women.
abstract: Markers of systemic inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule 1 [sICAM-1], and fibrinogen) have been associated with a greater risk of total and ischemic stroke, in addition to elevated blood pressure. However, the role of these inflammatory markers on stroke pathophysiology by hypertension status is uncertain.
  
  
  
  Blood samples were collected and assayed for hsCRP, sICAM-1, and fibrinogen among 27,330 initially healthy women from the Women's Health Study, and women were followed up from 1992 to 2013. Prior to randomization, the baseline questionnaire collected self-reported hypertension status, cardiovascular risk factors, and lifestyle factors. New cases of total, ischemic, and hemorrhagic stroke were updated annually through questionnaires and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models estimated overall associations between each inflammatory marker and stroke and separately stratified by hypertension status.
  
  
  
  We observed 629 incident total strokes over 477,278 person-years. In adjusted analyses, extreme quartiles of hsCRP and sICAM-1 were each associated with a significantly greater risk of total stroke (hsCRP: hazard ratios [HR] = 1.77, 95% confidence interval [CI]: 1.39-2.26; sICAM-1: HR = 1.28, 95% CI: 1.00-1.63). Fibrinogen was not associated with a significantly greater stroke risk. In analyses stratified by hypertension status, elevated hsCRP was associated with a nonstatistically significant greater risk of total stroke among prehypertensive and hypertensive women.
  
  
  
  These data indicate that hsCRP and sICAM-1 are associated with hypertension status and stroke risk among women. Further work should examine the role of inflammatory markers on ischemic stroke subtypes and clarify mechanisms.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; mjimenez11@partners.org.
authors.forename: Monik C
authors.initials: MC
authors.lastname: Jiménez
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA;
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA;
authors.forename: Gregory
authors.initials: G
authors.lastname: Kotler
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA;
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Everett
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA;
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA;
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA;
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Division of Aging, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications*; D015994:Incidence; D007249:Inflammation / Q000097:blood / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008875:Middle Aged; D020521:Stroke / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D002097:C-Reactive Protein
keywords: blood pressure; fibrinogen; high-sensitivity C-reactive protein; hypertension; intercellular adhesion molecule 1; ischemic stroke; prehypertension.