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Lawrence Ulanski, Thasarat Vajaranant, Charlotte Joslin; Stroke Risk in Advance Macular Degeneration from AREDS Data Set. Invest. Ophthalmol. Vis. Sci. 2013;54(15):232.
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© ARVO (1962-2015); The Authors (2016-present)
The AREDS dataset was analyzed to determine the relationship between AREDS category of disease and the risk of stoke to determine if there maybe a relationship between AMD category and risk for stroke.
The dbGaP Age-Related Eye Disease Study (AREDS) dataset, a longitudinal randomized clinical trial of high-dose antioxidants for prevention of age-related macular degeneration (AMD) in predominantly whites, was analyzed. AREDS (Category 1, 2, 3 and 4) was used to assess the hazard of baseline AMD status on self- reported, newly diagnosed stroke since the last study visit. The proportional hazard assumption among AMD categories was tested with Kaplan-Meier Survival Curves and the Log-Rank and Wilcoxon tests. The hazard ratio and 95% confidence interval (95% CI) for the effect of AMD on the hazard of incident stroke was estimated using multivariable Cox Proportional Hazard regression models, treating AMD as a categorical regression variable. Testing of null hypotheses and model building was conducted (SAS v9.3, Cary, NC) by comparing -2LogLikelihood (-2LL) model values among nested models (using a Chi-Square test with appropriate degrees of freedom).
Subject demographics are presented in Table 1. A total of 77 analyzed incident stroke events occurred, 42 (2.0%) in women and 35 (2.2%) in men during 12.5 years of follow-up. Proportional hazard ratio testing among AMD categories indicated a constant hazard ratio with time (Log-Rank, p = 0.23; and Wilcoxon p = 0.22 tests). Multivariable Cox regression analysis results and sex-stratified results are presented in Table 2. There is noted to be a significant dose-response increase in stroke risk in men based upon AMD category. Specifically, Categories 3 & 4 were associated with increased risk of stroke. (p<0.05) This was not seen in female subjects. Women demonstrate increased risk (p<0.001) for stroke associated with hypertension and diabetes. Significantly, stroke risk was not associated with BMI/obese, antioxidant treatment category, angina, or systolic/diastolic blood pressure.
While the incident of stroke was low, amongst this cohort advance AMD may serve as a risk marker for stroke in men. The difference in results between men and women may be related to differences in systemic disease pathogenesis between the sexes. Sex-stratified analyses with additional datasets are necessary to confirm these results.
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