title: Association of kidney disease measures with ischemic versus hemorrhagic strokes: pooled analyses of 4 prospective community-based cohorts.
abstract: OBJECTIVE
  Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke.
  
  
  METHODS
  We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression.
  
  
  RESULTS
  Among 29,595 participants (mean age, 61 [SD 12.5] years; 46% men; 17% black), 1261 developed stroke (12% hemorrhagic) during 280,549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95% confidence interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07) for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure.
  
  
  CONCLUSIONS
  Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations.
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Bakhtawar K
authors.initials: BK
authors.lastname: Mahmoodi
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuya
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Yinying
authors.initials: Y
authors.lastname: Sang
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: W T
authors.initials: WT
authors.lastname: Longstreth
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (B.K.M., K.M., Y.S., M.W., J.C.); Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., R.T.G.); Department of Public Health, Fujita Health University, Toyoake, Japan (H.Y.); Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.F.G.); Department of Medicine and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison (B.C.A.); George Institute, University of Sydney, Sydney, New South Wales, Australia (M.W.); Departments of Neurology and Epidemiology, University of Washington, Seattle (W.T.L.); Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology and Health Service, University of Washington and Group Health Research Institute, Group Health Cooperative, Seattle (B.M.P.); Division of General Internal Medicine, San Francisco VA Medical Center, University of California San Francisco (M.G.S.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.). coresh@jhu.edu.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000453:epidemiology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000453:epidemiology* / Q000503:physiopathology; D015897:Comorbidity; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000453:epidemiology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000145:classification / Q000453:epidemiology* / Q000503:physiopathology; D014481:United States / Q000453:epidemiology
keywords: cardiovascular; epidemiology; renal insufficiency, chronic; risk factors; stroke