Bakhtawar K Mahmoodi1, Hiroshi Yatsuya1, Kunihiro Matsushita1, Yinying Sang1, Rebecca F Gottesman1, Brad C Astor1, Mark Woodward1, W T Longstreth1, Bruce M Psaty1, Michael G Shlipak1, Aaron R Folsom1, Ron T Gansevoort1, Josef Coresh2. 1. 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.). 2. 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.
Abstract
BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: 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.
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