{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:23:27Z","timestamp":1793305407671,"version":"4.5.0"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Although increasing evidence suggests that trimethylamine N-oxide (TMAO) is associated with atherosclerosis, little is known about whether TMAO and its related metabolites (ie, choline, betaine, and carnitine) are associated with small vessel disease.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the association between TMAO and its related metabolites with features of cerebral small vessel disease, including white matter hyperintensity volume (WMHV) and acute lacunar infarction.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cross-sectional study included patients enrolled in the Specialized Programs of Translational Research in Acute Stroke biorepository. The registry included 522 patients with acute ischemic stroke who were 18 years or older who presented at the Massachusetts General Hospital or Brigham and Women\u2019s Hospital within 9 hours after onset between January 2007 and April 2010. The analyses in this study were conducted between November 2022 and April 2023.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Plasma TMAO, choline, betaine, and carnitine were measured by liquid chromatography\u2013tandem mass spectrometry.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n WMHV was quantified by a semiautomated approach using signal intensity threshold with subsequent manual editing. Ischemic stroke subtype was classified using the Causative Classification System.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 351 patients included in this study, the mean (SD) age was 69 (15) years; 209 patients (59.5%) were male and had a median (IQR) admission National Institute of Health Stroke Scale of 6 (3-13). The magnetic resonance imaging subgroup consisted of 291 patients with a mean (SD) age of 67 (15) years. Among these, the median (IQR) WMHV was 3.2 (1.31-8.4) cm\n 3<\/jats:sup>\n . TMAO was associated with WMHV after adjustment for age and sex (\u03b2, 0.15; 95% CI, 0.01-0.29;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). TMAO remained significant in a multivariate analysis adjusted for age, sex, hypertension, diabetes, and smoking (\u03b2, 0.14; 95% CI, 0-0.29;\n P<\/jats:italic>\n \u2009=\u2009.05). TMAO was associated with lacunar stroke but not other ischemic stroke subtypes in a model adjusted for age, sex, hypertension, diabetes, and smoking (OR, 1.67; 95% CI, 1.05-2.66;\n P<\/jats:italic>\n \u2009=\u2009.03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this observational study, TMAO was associated with cerebral small vessel disease determined by WMHV and acute lacunar infarction. The association was independent of traditional vascular risk factors.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.30446","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T11:36:18Z","timestamp":1692790578000},"page":"e2330446","source":"Crossref","is-referenced-by-count":18,"title":["Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke"],"prefix":"10.1001","volume":"6","author":[{"given":"Naruchorn","family":"Kijpaisalratana","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston"},{"name":"Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"},{"name":"Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Ament","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Bevers","sequence":"additional","affiliation":[{"name":"Divisions of Stroke, Cerebrovascular and Critical Care Neurology, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun M.","family":"Bhave","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Lucia","family":"Garcia Guarniz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine A.","family":"Couch","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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