Advanced Macular Degeneration Linked to Increased ICH

Susan Jeffrey

February 09, 2011

February 9, 2011 (Los Angeles, California) — A new report from the Rotterdam Study finds a link between advanced age-related macular degeneration (AMD) and an increased risk for intracerebral hemorrhage (ICH).

Researchers found that both the dry and the wet forms of late AMD were strongly and independently associated with ICH but not with cerebral infarction.

"This is a remarkable finding that has not been reported before," lead author Renske G. Wieberdink, MD, an epidemiologist at Erasmus Medical Center in Rotterdam, the Netherlands, said at a press conference here.

Dr. Renske G. Wieberdink

"However, we should be cautious when interpreting the results because although we reported a strong association, it's important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage."

Only if replicated in larger cohorts may the findings have clinical implications, she added.

Their report was presented here at the American Stroke Association International Stroke Conference 2011.

Common Mechanisms?

Both AMD and stroke frequently affect elderly populations, and several risk factors for these conditions overlap, including hypertension, smoking, elevated cholesterol levels, and carotid artery disease, the authors point out. "It has been hypothesized that stroke and AMD may have a common underlying pathway," Dr. Wieberdink said.

In this study, they examined the association between the presence of AMD and stroke risk and stroke subtypes by using the large population-based elderly cohort enrolled in the Rotterdam Study. The cohort includes 6207 participants who were 55 years of age or older and free of stroke at baseline between 1990 and 1993.

Participants were then continuously followed for stroke through linkage of the Rotterdam Study database with general practitioners' files and nursing home records. If a stroke was reported, hospital records were obtained to classify stroke subtype.

AMD was evaluated by using fundus photographs at baseline and at each follow-up visit. Severity of AMD was categorized into 5 stages ranging from 0, indicating no AMD, to stage 4. Stage 4 was further divided into what is known as atrophic ("dry") AMD or neovascular ("wet") AMD.

Follow-up for incident stroke was complete up to January 1, 2007. During that period (a total of 69,152 person-years of follow-up), 726 strokes occurred, including 397 cerebral infarctions and 59 intracerebral hemorrhages; stroke type for 270 was not specified.

After adjustment for potential confounders including systolic blood pressure, current smoking, and diabetes mellitus, the investigators found a "modest" association between stage 4 AMD and an increased risk for any stroke. However, late AMD, both dry and wet, was associated with a more than 6-fold increase in ICH, although not with cerebral infarction.

Risk for Stroke in Late-Stage AMD vs No AMD

Comparison Hazard Ratio (95% CI)
Stage 4 AMD (any stroke) 1.56 (1.08 - 2.26)
Late AMD (ICH) 6.11 (2.34 - 15.98)

CI = confidence interval

There was no association between early (stage 1 to 3) AMD and stroke or any subtype.

Dr. Wieberdink stressed that these results should be considered preliminary because of the relatively small number of events. Further, the mechanism of the relationship is unknown.

"We don't think there's a causal relationship between AMD and stroke," she said. "Instead, we think that AMD and bleeding stroke may result from a common underlying disease process. However, further research is required to further unravel the nature of the relationship between late AMD and stroke."

The follow-up period in this study predates some of the newer treatments for AMD, such as anti-vascular endothelial growth factor therapy, that may also affect stroke risk, Dr. Wieberdink noted.

Steven Greenberg, MD, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at Massachusetts General Hospital Stroke Research Center, moderated the press conference here.

Dr. Steven Greenberg

He also emphasized the preliminary nature of the findings but pointed out that if the relationship is real, it could affect clinical decision-making in these patients with AMD.

"If it were replicated and it was a clear study, the most straightforward question that patients want to know is whether this should affect your decision to use blood-thinning agents, at the mild end, like aspirin, or at the strong end, like warfarin or some of the other strong anticoagulant agents," he said.

Commenting on the findings, Philip B. Gorelick, MD, MPH, John S. Garvin Professor, head of the Department of Neurology and Rehabilitation, and director of the Center for Stroke Research at the University of Illinois College of Medicine, Chicago, also agreed that further replication of the results is required.

"Advanced stages of AMD may be associated with brain hemorrhage, but it's too early to know for sure because if you look at the confidence intervals based on the estimate of risk here, they're wide, and we're going to need further validation of this finding in other large datasets."

Because risk factors for both of these conditions are similar, he noted, "it would pay, currently, to control those risk factors to try to reduce the risk of brain hemorrhage, which is heavily related to blood pressure, so blood pressure should be given special attention to be controlled."

The researchers have disclosed no relevant financial relationships.

American Stroke Association International Stroke Conference 2011: Abstract #27. Presented February 9, 2011.

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