School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
Department of Chronic Disease Control and Prevention, Changshu Center for Disease Control and Prevention, Suzhou, China.
J Intern Med. 2023 Jan;293(1):110-120. doi: 10.1111/joim.13572. Epub 2022 Oct 6.
Trimethylamine N-oxide (TMAO) is a gut-derived atherogenic metabolite. However, the role of TMAO and its precursors in the development of stroke remains unclear. We aimed to examine the associations between metabolites in TMAO biosynthesis and stroke risk.
A nested case-control study was performed in a community-based cohort (2013-2018, n = 16,113). We included 412 identified stroke cases and 412 controls matched by age and sex. Plasma carnitine, choline, betaine, trimethyl lysine (TML), and TMAO were measured by ultrahigh performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) between these biomarkers and stroke risk.
After adjustment for body mass index, smoking, hypertension, educational attainment, and estimated glomerular filtration rate, the corresponding OR for the highest versus lowest quartile was 1.74 (95% CI: 1.16-2.61, P trend = 0.006) for total stroke and 1.81 (95% CI: 1.14-2.86, P trend = 0.020) for ischemic stroke in an essentially linear dose-response fashion. A significant association between TMAO and nonischemic stroke was shown as a J-shape with OR for the highest versus second quartile of 5.75 (95% CI: 1.73-19.1). No meaningful significant risk association was found among plasma carnitine, choline, betaine, and TML with stroke risk.
Increased TMAO was associated with higher stroke risk in the community-based population, whereas the TMAO precursors carnitine, choline, betaine, and TML were not associated. Further studies are warranted to confirm these findings and to further elucidate the role of TMAO in the development of stroke.
三甲胺 N-氧化物（TMAO）是一种肠道衍生的动脉粥样硬化代谢物。然而，TMAO 及其前体在中风发展中的作用尚不清楚。我们旨在研究 TMAO 生物合成代谢物与中风风险之间的关联。
在社区为基础的队列中进行了一项嵌套病例对照研究（2013-2018 年，n = 16113）。我们纳入了 412 例确诊的中风病例和 412 例年龄和性别匹配的对照。通过超高效液相色谱-串联质谱法测量血浆肉碱、胆碱、甜菜碱、三甲赖氨酸（TML）和 TMAO。使用条件逻辑回归分析计算这些生物标志物与中风风险之间的比值比（OR）及其 95%置信区间（CI）。
在调整体重指数、吸烟、高血压、教育程度和估计肾小球滤过率后，总中风的最高与最低四分位比的相应 OR 为 1.74（95%CI：1.16-2.61，P 趋势=0.006），缺血性中风的相应 OR 为 1.81（95%CI：1.14-2.86，P 趋势=0.020），呈基本线性剂量反应模式。TMAO 与非缺血性中风之间存在显著的关联，呈 J 形，最高与第二四分位比的 OR 为 5.75（95%CI：1.73-19.1）。血浆肉碱、胆碱、甜菜碱和 TML 与中风风险之间无明显的显著风险关联。
在社区人群中，TMAO 水平升高与中风风险增加相关，而 TMAO 的前体肉碱、胆碱、甜菜碱和 TML 与中风风险无关。需要进一步的研究来证实这些发现，并进一步阐明 TMAO 在中风发展中的作用。
