title: Carotid stiffness is associated with incident stroke: a systematic review and individual participant data meta-analysis.
abstract: BACKGROUND
  Carotid stiffening is considered a key element in the pathogenesis of stroke. However, results of studies evaluating the association between carotid stiffness and incident stroke have been inconsistent.
  
  
  OBJECTIVE
  This study investigated whether carotid stiffness (as determined by ultrasonography) is associated with incident stroke and whether this association is independent of aortic stiffness as estimated by carotid-femoral pulse wave velocity (cfPWV). Additionally, we evaluated the incremental value of carotid stiffness for stroke risk prediction beyond Framingham risk factors and cfPWV.
  
  
  METHODS
  This study included a systematic review and meta-analyses of aggregate and individual participant data (IPD), the latter of which was obtained by requesting individual-level data of all cohort studies with available data on carotid stiffness and cfPWV.
  
  
  RESULTS
  Ten studies (n = 22,472) were included in the aggregate data meta-analysis and 4 (n = 4,540) in the IPD meta-analysis. After adjusting for cardiovascular (CV) factors, the aggregate data meta-analysis showed that greater carotid stiffness (per SD) was associated with stroke (hazard ratio: 1.18; 95% confidence interval: 1.05 to 1.33). In addition, carotid stiffness was associated with total CV events and CV and all-cause mortality, but not with coronary heart disease events. In the IPD meta-analysis, additional adjustment for cfPWV did not materially change these associations. Carotid stiffness did improve stroke risk prediction beyond Framingham and cfPWV (integrative discrimination improvement: 0.4 percentage point [95% confidence interval: 0.1 to 0.6 percentage point] and continuous net reclassification improvement: 18.6% [95% confidence interval: 5.8% to 31.3%]).
  
  
  CONCLUSIONS
  Carotid stiffness is associated with incident stroke independently of CV factors and aortic stiffness. In addition, carotid stiffness improves stroke risk prediction beyond Framingham and aortic stiffness.
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: van Sloten
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Sedaghat
authors.affiliation: Inserm U970, HEGP, AP-HP, Université Paris-Descartes, Paris, France; Department of Pharmacology, Georges Pompidou European Hospital, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Laurent
authors.affiliation: Hôpital Manhès, Paris, France.
authors.forename: Gérard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Centre d'Investigations Préventives et Cliniques (IPC Center), Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pannier
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattace-Raso
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Inserm U970, HEGP, AP-HP, Université Paris-Descartes, Paris, France; Department of Pharmacology, Georges Pompidou European Hospital, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, the Netherlands. Electronic address: cda.stehouwer@mumc.nl.
authors.forename: Coen D A
authors.initials: CDA
authors.lastname: Stehouwer
mesh_terms: D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014943:Global Health; D006801:Humans; D015994:Incidence; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000503:physiopathology; D014463:Ultrasonography; D059289:Vascular Stiffness
keywords: arterial stiffness; cardiovascular disease; risk classification