Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis

• Type of Material: Article
• Authors: Hyung-Min Kwon, Seoul National University; Michael Lynn, Emory University; Tanya N. Turan, Medical University of South Carolina; Colin P. Derdeyn, Washington University; David Fiorella, State University of New York; Bethany F. Lane, Morehouse School of Medicine; Jean Montgomery, Emory University; L. Scott Janis, National Institute of Health; Zoran Rumboldt, Medical University of South Carolina; Marc I. Chimowitz, Medical University of South Carolina
• Language: English
• Date: 2016-01-01
• Publisher: American Medical Association (AMA)
• Publication Version: Final Published Version
• Copyright Statement: © 2018 American Medical Association. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1001/jamaneurol.2015.3145
• Title of Journal or Parent Work: JAMA Neurology
• ISSN: 2168-6149
• Volume: 73
• Issue: 1
• Start Page: 36
• End Page: 42
• Grant/Funding Information: Walgreens pharmacies provided study medications except rosuvastatin to patients at a discounted price (paid for by the study).; This research was also supported by the Investigator-Sponsored Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to study patients.; The Regulatory and Clinical Research Institute (RCRI) (Minneapolis, MN) provided assistance in designing the site monitoring processes and perform the site monitoring visits.; The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Albuquerque, NM) handled the procurement, labeling, distribution, and inventory management of the study devices and rosuvastatin.; Vendors: INTERVENT provided the lifestyle modification program to the study at a discounted rate.; In addition, the following Clinical and Translational Science Awards, funded by the National Institutes of Health, provided local support for the evaluation of patients in the trial: Medical University of South Carolina (UL1RR029882), University of Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and University of California, San Francisco (UL1RR024131).; Corporate Support: Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third party device distribution, site monitoring, and study auditing.; This study was funded by a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS).
• Keywords: Cerebrovascular circulation; Atherosclerosis; Lacunar infarct; Risk factors; Vascular disease
• Research Categories: Biology, Bioinformatics; Health Sciences, Radiology; Biology, Neuroscience

Abstract

Importance: Intracranial large artery stenosis (ICAS) and small vessel disease (SVD) may coexist. There are limited data on the frequency and risk factors for coexistent SVD and the effect of SVD on stroke recurrence in patients receiving medical treatment for ICAS. Objective: To investigate the frequency and risk factors for SVD and the effect of SVD on stroke recurrence in patients with ICAS. Design, Setting, and Participants: A post hoc analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, a prospective, multicenter clinical trial. Among 451 participants, 313 (69.4%) had baseline brain magnetic resonance imaging scans read centrally for SVD that was defined by any of the following: old lacunar infarction, grade 2 to 3 on the Fazekas scale (for high-grade white matter hyperintensities), or microbleeds. Patient enrollment in SAMMPRIS began November 25, 2008, and follow-up ended on April 30, 2013. Data analysis for the present study was performed from May 13, 2014, to July 29, 2015. Main Outcomes and Measures: Risk factors in patients with vs without SVD and the association between SVD and other baseline risk factors with any ischemic stroke and ischemic stroke in the territory of the stenotic artery determined using proportional hazards regression. Results: Of 313 patients, 155 individuals (49.5%) had SVD noted on baseline magnetic resonance imaging. Variables that were significantly higher in patients with SVD, reported as mean (SD), included age, 63.5 (10.5) years (P < .001), systolic blood pressure, 149 (22) mmHg (P < .001), glucose level, 130 (50) mg/dL (P = .03), and lower Montreal Cognitive Assessment scores (median, ≥24 [interquartile range, 20–26]; P = .02).Other significant variables were the number of patients with diabetes mellitus (88 of 155 [56.8%]; P = .003), coronary artery disease (46 [29.7%]; P = .004), stroke before the qualifying event (59 [38.1%]; P < .001), old infarct in the territory of the stenotic intracranial artery (88 [56.8%]; P < .001), and receiving antithrombotic therapy at the time of the qualifying event (109 [70.3%]; P = .005). The association between SVD and any ischemic stroke was nearly significant in the direction of a higher risk (18 [23.7%]); P = .07) for patients with SVD. On bivariate analysis, SVD was not associated with an increased risk on multivariable analyses (hazard ratio, 1.7 [95%CI, 0.8–3.8]; P = .20). In addition, SVD was not associated with an increased risk of stroke in the territory on either bivariate or multivariable analyses. Conclusions and Relevance: Although SVD is common in patients with ICAS, the presence of SVD on baseline magnetic resonance imaging is not independently associated with an increased risk of stroke in patients with ICAS.