Small brain lesions and incident stroke and mortality: A cohort study

Background: Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. Objective: To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs). Design: Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. Setting: Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. Participants: 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. Measurements: Lesions on MRI (by size),WMHscore (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. Results: Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). Limitation: Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. Conclusion: Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates.