The application describes a population-based case-cohort study to determine whether retinal arteriolar changes (generalized narrowing, focal narrowing and arterio-venous nicking) and retinopathy are associated with 10-year stroke-and ischemic heart disease-related mortality. The study population will be selected from participants of the Beaver Dam Eye Study, a well-characterized population of predominantly white persons aged 43-86 years at the baseline examination in 1988-90. Cases are defined as participants who have died from either stroke or ischemic heart disease since the baseline examination. Three participants per case will be selected from the cohort at baseline as controls, matched on gender and 5-year age intervals to cases. Focal arteriolar narrowing, arteriovenous nicking and retinopathy have been graded to baseline using a standardized photographic grading protocol. To evaluate generalized arteriolar narrowing, a method modified from the Atherosclerosis Risk in Communities Study will be used. Retinal photographs will be digitized and processed using a high-resolution scanner. Retinal arteriole and venule widths will then be measured with the help of a computer program based on pixel density contrast between the vessel and the background retina. Finally, the average width of the arterioles will be summarized as a retinal arteriole to venule ratio (AVR). Standard case-control methodology will be applied to calculate the relative odds of association between generalized retinal arteriolar narrowing (using different categories of AVR) and other changes with stroke-and ischemic heart disease-related mortality. Logistic regression models controlling for potential confounders (e.g., blood pressure, serum lipid levels) will be employed to evaluate the independent association between retinal arteriolar characteristics and stroke- and ischemic heart disease mortality. Data from this study will improve the understanding of the association between microvascular characteristics and cardiovascular mortality.
