title: Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort.
abstract: BACKGROUND
  Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis.
  
  
  METHODS
  We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified.
  
  
  RESULTS
  Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 - 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 - 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 - 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved.
  
  
  CONCLUSIONS
  Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.
authors.affiliation: Division of Nephrology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN, 55415, USA. james.wetmore@hcmed.org.
authors.forename: James B
authors.initials: JB
authors.lastname: Wetmore
authors.affiliation: Department of Biostatistics, University of Kansas School of Medicine, Kansas City, KS, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Mahnken
authors.affiliation: Department of Biostatistics, University of Kansas School of Medicine, Kansas City, KS, USA.
authors.forename: Milind A
authors.initials: MA
authors.lastname: Phadnis
keywords: Dialysis; ESRD; Medicare; Mortality; Stroke; USRDS