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Observational Study
. 2023 Aug 1;6(8):e2330446.
doi: 10.1001/jamanetworkopen.2023.30446.

Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke

Naruchorn Kijpaisalratana  1   2   3   4 , Zsuzsanna Ament  1   2 , Matthew B Bevers  5 , Varun M Bhave  6 , Ana-Lucia Garcia Guarniz  2 , Catharine A Couch  7 , M Ryan Irvin  7 , W Taylor Kimberly  1   2   6
Affiliations
Observational Study

Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke

Naruchorn Kijpaisalratana et al. JAMA Netw Open. .

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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's 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.

Exposures: Plasma TMAO, choline, betaine, and carnitine were measured by liquid chromatography-tandem mass spectrometry.

Main outcomes and measures: 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.

Results: 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) cm3. TMAO was associated with WMHV after adjustment for age and sex (β, 0.15; 95% CI, 0.01-0.29; P < .001). TMAO remained significant in a multivariate analysis adjusted for age, sex, hypertension, diabetes, and smoking (β, 0.14; 95% CI, 0-0.29; P = .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; P = .03).

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bevers reported receiving grants from National Institute of Neurological Disorders and Stroke outside the submitted work. Dr Kimberly reported receiving grants from National Institutes of Health during the conduct of the study and grants from Biogen, NControl Therapeutics, and Hyperfine and personal fees from Acasti Pharma, Astrocyte Pharmaceuticals, and Woolsey Pharmaceuticals outside the submitted work. Additionally, Dr Kimberly reported having a patent for PCT 16/486,687 issued. No other disclosures were reported.

Figures

Figure.
Figure.. Plasma Trimethylamine-N-Oxide (TMAO) Level Over Time in Patients With High and Low White Matter Hyperintensity (WMH)
See this image and copyright information in PMC

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