Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: A meta-analysis.

Duncan Wilson,Vincent Thijs,Phillip Rayson,Roland Veltkamp,David J Werring,Felix Fluri,Yining Huang,Hans Rolf Jäger,Peter M Rothwell,Young Dae Kim,Solveig Horstmann,Gareth Ambler,Andreas Charidimou,Toshio Imaizumi,Ka Sing Wong,Stéphanie Grégoire ,Yong Seok Lee ,Hiroyuki Naka ,Zoë Fox ,Vincent I H Kwa

doi:10.1212/wnl.0000000000003183

Abstract

Objective:To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA.Methods:We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis.Results:We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively).Conclusions:CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories.

Highlights

Twelve of the 15 studies provided data on cerebral microbleed (CMB) at the time of the initial ischemic stroke (IS)/TIA fully stratified into number categories and location
CMB presence was more prevalent, with higher burden, in the Eastern cohorts compared to Western cohorts
We found only weak evidence for a confounding effect of hypertension; as expected, the relative risk associated with baseline CMBs on future IS risk is attenuated in studies with a higher prevalence of hypertension

Summary

Introduction

Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Wellcome Trust.

Methods

Results

Discussion

Conclusion