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Tien Yin Wong, MD, MPH; Ronald Klein, MD, MPH; A. Richey Sharrett, MD, DrPH; David J. Couper, PhD; Barbara E. K. Klein, MD, MPH; Duan-Ping Liao, MD, PhD; Larry D. Hubbard, MAT; Thomas H. Mosley, PhD; for the ARIC Investigators

JAMA. 2002;288:67-74.

Context  White matter lesions (WMLs) detected on cerebral imaging scans have been hypothesized to have a microvascular etiology and to precede the development of clinical stroke. However, few clinical data are available to support these hypotheses.

Objective  To examine the relationship of WMLs, retinal microvascular abnormalities, and incident clinical stroke in healthy, middle-aged men and women.

Design and Setting  The Atherosclerosis Risk in Communities Study (ARIC), a prospective, population-based cohort study conducted in 4 US communities and initiated in 1987-1989.

Participants  A total of 1684 persons aged 51 to 72 years who had cerebral magnetic resonance imaging (MRI) and retinal photography at the third examination (1993-1995).

Main Outcome Measures  Odds of WMLs, defined by standardized methods from MRI, by presence or absence of specific retinal microvascular abnormality (eg, microaneurysm, retinal hemorrhage) on retinal photograph; incident clinical stroke, ascertained after a median follow-up of 4.7 years, according to presence or absence of WMLs and retinopathy.

Results  Persons with retinopathy were more likely to have WMLs than those without retinopathy (22.9% vs 9.9%; odds ratio, 2.5; 95% confidence interval [CI], 1.5-4.0, adjusted for age, sex, race, and vascular risk factors). The 5-year cumulative incidence of clinical stroke was higher in persons with vs without WMLs (6.8% vs 1.4%; adjusted relative risk [RR], 3.4; 95% CI, 1.5-7.7) and in persons with vs without retinopathy (8.0% vs 1.4%; adjusted RR, 4.9; 95% CI, 2.0-11.9). Persons with both WMLs and retinopathy had a significantly higher 5-year cumulative incidence of stroke than those without either WMLs or retinopathy (20.0% vs 1.4%; adjusted RR, 18.1; 95% CI, 5.9-55.4).

Conclusions  In this cohort, middle-aged persons with cerebral WMLs detected on MRI were more likely to have retinal microvascular abnormalities and to have an increased risk of clinical stroke than people without WMLs. The risk of stroke was higher when retinopathy was simultaneously present in persons with WMLs.

Author Affiliations: Department of Ophthalmology, University of Wisconsin, Madison (Drs Wong, R. Klein, B. Klein, and Mr Hubbard); Singapore National Eye Center and Department of Ophthalmology, National University of Singapore (Dr Wong); Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Md (Dr Wong); National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Sharrett); Department of Biostatistics, University of North Carolina, Chapel Hill (Dr Couper); Department of Health Evaluation Sciences, Pennsylvania State University College of Medicine, Hershey (Dr Liao); and Department of Medicine, University of Mississippi Medical Center, Jackson (Dr Mosley).

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