Decreased Glomerular Filtration Rate Is a Risk Factor for Hemorrhagic But Not for Ischemic Stroke

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Abstract
Persons with early stages of chronic kidney disease, defined by a decreased glomerular filtration rate (GFR), have an increased risk of cardiovascular disease. It is unclear whether decreased GFR is a risk factor for stroke. We assessed the association between GFR and stroke in a prospective population-based cohort study. The study was based on 4937 participants of the Rotterdam Study who at baseline (1990 to 1993) were aged 55 years or over, free from stroke, and had serum creatinine assessment. GFR was estimated with the Cockcroft-Gault equation. Follow-up for incident cerebrovascular disease was complete until January 1, 2005. Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders and results were expressed as hazard ratios with 95% CIs. During an average follow-up of 10.2 years, 586 strokes (338 ischemic, 44 hemorrhagic, and 204 unspecified strokes) occurred. We found no association between GFR and risk of overall stroke or risk of ischemic stroke. In contrast, with decreasing GFR, the risk of hemorrhagic stroke strongly increased; the age- and sex-adjusted hazard ratio for hemorrhagic stroke was 4.10 (95% CI, 1.25 to 13.42) for lowest versus highest quartile of GFR, and there was a clear and highly significant dose-effect relationship. Adjustment for other vascular risk factors only slightly attenuated this association. Decreased GFR is a strong risk factor for hemorrhagic, but not ischemic stroke.