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Decreased glomerular filtration rate is a risk factor for hemorrhagic but not for ischemic stroke: the Rotterdam

Michiel J Bos¹, Peter J Koudstaal, Albert Hofman

¹Department of Epidemiology & Biostatistics, Erasmus Medical Center, Dr. Molewaterplein 50, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

|October 27, 2007

Insights

Reduced kidney function, indicated by a lower glomerular filtration rate (GFR), strongly increases the risk of hemorrhagic stroke, but not ischemic stroke. This finding highlights a significant association between chronic kidney disease and stroke subtypes.

Area of Science:

Nephrology
Neurology
Epidemiology

Background:

Chronic kidney disease (CKD) is linked to increased cardiovascular disease risk.
The relationship between decreased glomerular filtration rate (GFR) and stroke risk remains unclear.
Early stages of CKD are defined by reduced GFR.

Purpose of the Study:

To investigate the association between estimated glomerular filtration rate (eGFR) and the risk of overall stroke.
To determine if reduced eGFR is a risk factor for specific stroke subtypes, namely ischemic and hemorrhagic stroke.
To assess the impact of declining kidney function on cerebrovascular disease incidence in an older population.

Main Methods:

Prospective, population-based cohort study (Rotterdam Study) including 4937 participants aged 55+.
Glomerular filtration rate (GFR) estimated using the Cockcroft-Gault equation from serum creatinine.
Incident cerebrovascular disease events prospectively followed until January 1, 2005, analyzed with Cox proportional hazards models.

Main Results:

Over 10.2 years of follow-up, 586 strokes occurred (338 ischemic, 44 hemorrhagic).
No significant association was found between GFR and overall or ischemic stroke risk.
A strong, dose-dependent association was observed between decreasing GFR and increased risk of hemorrhagic stroke (HR 4.10 for lowest vs. highest GFR quartile).

Conclusions:

Decreased glomerular filtration rate (GFR) is identified as a significant risk factor for hemorrhagic stroke.
Reduced GFR is not associated with an increased risk of ischemic stroke.
This study underscores the importance of kidney function assessment in predicting hemorrhagic stroke risk.

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Abstract

Background And Purpose:

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.

Methods:

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.

Results:

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.

Conclusions:

Decreased GFR is a strong risk factor for hemorrhagic, but not ischemic stroke.

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