Abstract

Introduction: Silent brain infarction (SBI) on magnetic resonance imaging (MRI) is relatively frequently detected but of uncertain clinical significance. Hypothesis: We hypothesized that a pooled estimate from all relevant published and unpublished sources will demonstrate SBI to be an independent risk factor for future stroke. Methods: We performed a systematic review and meta-analysis to summarize the association between MRI-defined SBI and future stroke. We searched for relevant literature in Ovid MEDLINE, Ovid Embase, and the Cochrane Library Database from inception to April 3, 2015. All cohort studies involving adults with MRI detection of SBI who were subsequently followed for incident clinically-defined stroke were eligible. Study data and quality assessment was recorded in duplicate with disagreements in data extraction resolved by a third reader. Results: We studied 14,764 subjects from 13 studies with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% CI 2.24-3.86, P<0.0001; Q=39.649, P<0.0001, Figure Panel A). In the 8 studies of 10,427 subjects providing cardiovascular risk factor-adjusted hazard ratios (HR), SBI was an independent predictor of incident stroke (HR of 2.08 [95% CI 1.69-2.56, P<0.0001, Figure Panel B]; Q=8.99, P=0.253). In a subgroup analysis pooling 9,483 stroke-free individuals from large population-based studies, SBI was present in ∼18% of participants and remained a strong predictor of future stroke (HR 2.06 [95% CI 1.64-2.59], p<0.01). A potential limitation of the existing literature was that MRI techniques for detecting SBI were variable across studies and were detected using older generation MRI equipment. Conclusion: SBI is present in approximately 1 in 5 stroke-free older adults and is associated with 2-fold increased risk of future stroke.

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