Frontiers in Neurology (Apr 2021)

Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers

  • Yiyi Chen,
  • Yiyi Chen,
  • Yiyi Chen,
  • Yiyi Chen,
  • Jie Xu,
  • Jie Xu,
  • Jie Xu,
  • Jie Xu,
  • Yuesong Pan,
  • Yuesong Pan,
  • Yuesong Pan,
  • Yuesong Pan,
  • Hongyi Yan,
  • Hongyi Yan,
  • Hongyi Yan,
  • Hongyi Yan,
  • Jing Jing,
  • Jing Jing,
  • Jing Jing,
  • Jing Jing,
  • Jing Jing,
  • Yingying Yang,
  • Yingying Yang,
  • Yingying Yang,
  • Yingying Yang,
  • Xing Wang,
  • Xing Wang,
  • Xing Wang,
  • Xing Wang,
  • Huijuan Wan,
  • Huijuan Wan,
  • Huijuan Wan,
  • Huijuan Wan,
  • Ying Gao,
  • Ying Gao,
  • Ying Gao,
  • Ying Gao,
  • Shangrong Han,
  • Shangrong Han,
  • Shangrong Han,
  • Shangrong Han,
  • Xi Zhong,
  • Xi Zhong,
  • Xi Zhong,
  • Xi Zhong,
  • Chenhui Liu,
  • Chenhui Liu,
  • Chenhui Liu,
  • Chenhui Liu,
  • Jingtao Pi,
  • Jingtao Pi,
  • Jingtao Pi,
  • Jingtao Pi,
  • Zhengyang Li,
  • Zhengyang Li,
  • Zhengyang Li,
  • Zhengyang Li,
  • Biyang Luo,
  • Biyang Luo,
  • Biyang Luo,
  • Biyang Luo,
  • Guangyao Wang,
  • Guangyao Wang,
  • Guangyao Wang,
  • Guangyao Wang,
  • Yilong Zhao,
  • Yilong Zhao,
  • Yilong Zhao,
  • Yilong Zhao,
  • Nan Wang,
  • Nan Wang,
  • Nan Wang,
  • Nan Wang,
  • Jinxi Lin,
  • Jinxi Lin,
  • Jinxi Lin,
  • Jinxi Lin,
  • Xia Meng,
  • Xia Meng,
  • Xia Meng,
  • Xia Meng,
  • Xingquan Zhao,
  • Xingquan Zhao,
  • Xingquan Zhao,
  • Xingquan Zhao,
  • Liping Liu,
  • Liping Liu,
  • Liping Liu,
  • Liping Liu,
  • Wei Li,
  • Wei Li,
  • Wei Li,
  • Wei Li,
  • Yong Jiang,
  • Yong Jiang,
  • Yong Jiang,
  • Yong Jiang,
  • Zixiao Li,
  • Zixiao Li,
  • Zixiao Li,
  • Zixiao Li,
  • Xinmiao Zhang,
  • Xinmiao Zhang,
  • Xinmiao Zhang,
  • Xinmiao Zhang,
  • Xiaomeng Yang,
  • Xiaomeng Yang,
  • Xiaomeng Yang,
  • Xiaomeng Yang,
  • Ruijun Ji,
  • Ruijun Ji,
  • Ruijun Ji,
  • Ruijun Ji,
  • Chunjuan Wang,
  • Chunjuan Wang,
  • Chunjuan Wang,
  • Chunjuan Wang,
  • Hao Li,
  • Hao Li,
  • Hao Li,
  • Hao Li,
  • Penglian Wang,
  • Penglian Wang,
  • Penglian Wang,
  • Penglian Wang,
  • Huaguang Zheng,
  • Huaguang Zheng,
  • Huaguang Zheng,
  • Huaguang Zheng,
  • Weizhong Ji,
  • Xueli Cai,
  • Songdi Wu,
  • Xinsheng Han,
  • Yongjun Wang,
  • Yongjun Wang,
  • Yongjun Wang,
  • Yongjun Wang,
  • Yilong Wang,
  • Yilong Wang,
  • Yilong Wang,
  • Yilong Wang

DOI
https://doi.org/10.3389/fneur.2021.648702
Journal volume & issue
Vol. 12

Abstract

Read online

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds.Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions.Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0–2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1–2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9–1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease.Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.

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