Last Updated: 2007-12-06 16:25:53 -0400 (Reuters Health)

NEW YORK (Reuters Health) – More than 10 years of follow-up in the ongoing, population-based Rotterdam Study shows that a low glomerular filtration rate (GFR) is associated with a more than 4-fold increase in risk of hemorrhagic stroke — but not ischemic stroke.

The study findings are based on 4,937 participants in the Rotterdam Study who had serum creatinine levels measured at baseline. Subjects were aged 55 and older and free from stroke.

Average follow-up was 10.2 years, during which there were 586 strokes. Of these, 338 were ischemic strokes, 44 were hemorrhagic and 204 were unspecified, Dr. Monique M. B. Bretler and colleagues at Erasmus Medical Center in Rotterdam report in the December issue of Stroke.

The team found that there was no increased risk of stroke overall or increased risk of ischemic stroke with low GFR. However, with decreasing GFR, the risk of hemorrhagic stroke strongly increased. After adjusting for age and sex, the hazard ratio for hemorrhagic stroke was 4.10 for the lowest versus highest quartile of GFR, with a "clear and highly significant dose-effect relationship."

The investigators offer two possible explanations for the link between low GFR and hemorrhagic stroke. They propose that "decreased GFR may be a marker of cerebral small vessel disease, which is presumed to be the main pathophysiological mechanism in the majority of brain hemorrhages, whereas it plays a much smaller role in brain infarctions."

A second hypothesis is that chronic kidney disease leads to hemorrhagic stroke pathophysiology. "An important sequel of chronic kidney disease is platelet dysfunction. This becomes apparent by prolonged bleeding time, mucocutaneous ecchymoses, and mucosal oozing in patients with severe chronic kidney disease. It is possible that a slightly decreased GFR also influences platelet function, which might explain the increased risk of hemorrhagic stroke in persons with decreased GFR," Dr. Bretler and colleagues propose.

"We think this is an important finding because our knowledge of causes of hemorrhagic stroke is very limited," they observe.

Stroke 2007;38:3127-3132.