White matter hyperintensity burden in acute stroke patients differs by ischemic stroke subtype
Anne‐Katrin Giese, Markus D. Schirmer, Adrian V. Dalca, Ramesh Sridharan, Kathleen Donahue, Marco Nardin, Robert E. Irie, Elissa C. McIntosh, Steven J. T. Mocking, Huichun Xu, John W. Cole, Eva Giralt‐Steinhauer, Jordi Jiménez-Conde, Christina Jern, Dawn Kleindorfer, Robin Lemmens, Johan Wassélius, Arne Lindgren, Tatjana Rundek, Ralph L. Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Słowik, Vincent Thijs, Bradford B. Worrall, Daniel Woo, Steven J. Kittner, Patrick F. McArdle, Braxton D. Mitchell, Jonathan Rosand, James F. Meschia, Ona Wu, Polina Golland, Natalia S. Rost, Anne‐Katrin Giese, Markus D. Schirmer, Adrian V. Dalca, Ramesh Sridharan, Kathleen Donahue, Marco Nardin, Robert E. Irie, Elissa C McIntos, Steven J. T. Mocking, Huichun Xu, John W. Cole, Eva Giralt‐Steinhauer, Jordi Jiménez-Conde, Christina Jern, Dawn Kleindorfer, Robin Lemmens, Johan Wassélius, Arne Lindgren, Tatjana Rundek, Ralph L. Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Słowik, Vincent Thijs, Bradford B. Worrall, Daniel Woo, Patrick F. McArdle, Braxton D. Mitchell, Jonathan Rosand
Abstract
<h3>Objective</h3> To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). <h3>Methods</h3> For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool–based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. <h3>Results</h3> Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all <i>p</i> < 0.001). Median WMHv in all patients with AIS was 5.86 cm<sup>3</sup> (interquartile range 2.18–14.61 cm<sup>3</sup>) and differed significantly across CCS subtypes (<i>p</i> < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all <i>p</i> < 0.001), and diabetes mellitus (<i>p</i> = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (<i>p</i> < 0.001). <h3>Conclusion</h3> In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.