Brain Hemorrhage Risk Higher With Late Macular Degeneration

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

Dr. Renske G. Wieberdink

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.