Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.
Department of Neurology, Massachusetts General Hospital, Boston.
JAMA Netw Open. 2023 Aug 1;6(8):e2330446. doi: 10.1001/jamanetworkopen.2023.30446.
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.
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.
Plasma TMAO, choline, betaine, and carnitine were measured by liquid chromatography-tandem mass spectrometry.
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.
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).
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.
虽然越来越多的证据表明三甲胺 N-氧化物（TMAO）与动脉粥样硬化有关，但关于 TMAO 及其相关代谢物（即胆碱、甜菜碱和肉碱）是否与小血管疾病有关知之甚少。
评估 TMAO 及其相关代谢物与脑小血管疾病特征（包括脑白质高信号体积（WMHV）和急性腔隙性梗死）之间的关联。
设计、地点和参与者：这项横断面研究纳入了专门的急性中风转化研究生物库中的患者登记。该登记册包括 522 名年龄在 18 岁或以上的急性缺血性中风患者，他们在 2007 年 1 月至 2010 年 4 月期间在发病后 9 小时内于马萨诸塞州总医院或布莱根妇女医院就诊。本研究的分析于 2022 年 11 月至 2023 年 4 月进行。
通过液相色谱-串联质谱法测量血浆 TMAO、胆碱、甜菜碱和肉碱。
WMHV 通过使用信号强度阈值的半自动方法进行量化，随后进行手动编辑。采用病因分类系统对缺血性中风亚型进行分类。
在这项研究中，纳入了 351 名患者，平均（标准差）年龄为 69（15）岁；209 名患者（59.5%）为男性，中位（IQR）入院国立卫生研究院中风量表评分为 6（3-13）。磁共振成像亚组由 291 名平均（标准差）年龄为 67（15）岁的患者组成。在这些患者中，WMHV 的中位数（IQR）为 3.2（1.31-8.4）cm3。TMAO 在调整年龄和性别后与 WMHV 相关（β，0.15；95%CI，0.01-0.29；P<0.001）。在调整年龄、性别、高血压、糖尿病和吸烟的多变量分析中，TMAO 仍然显著（β，0.14；95%CI，0-0.29；P=0.05）。在调整年龄、性别、高血压、糖尿病和吸烟的模型中，TMAO 与腔隙性中风相关，但与其他缺血性中风亚型无关（OR，1.67；95%CI，1.05-2.66；P=0.03）。
在这项观察性研究中，TMAO 与通过 WMHV 和急性腔隙性梗死确定的脑小血管疾病相关。该关联独立于传统的血管危险因素。
