We aimed to determine the serum concentrations of altered compounds to understand the changes in metabolism and pathophysiology that occur prior to thrombotic stroke. In this prospective cohort study, high-resolution metabolomics (HRM) was employed to analyze serum samples obtained from patients at risk of stroke (n = 99) and non-risk controls (n = 301). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were employed to identify the discriminant metabolic profiles and to determine significantly different metabolites between healthy control and stroke risk groups. PLS-DA satisfactorily separated the stroke risk sera from control sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking, diabetes mellitus, or insulin sensitivity. A group of 35 metabolites, most of them amino acids, that were capable of discriminating stroke risk sera from controls were identified using untargeted metabolomics. Further, the targeted metabolomics approach confirmed that the quantified concentrations of l-tryptophan, 3-methoxytyramine, methionine, homocysteinesulfinic acid, cysteine, isoleucine, carnitine, arginine, linoleic acid, and sphingosine were specifically elevated in the sera of patients who were later diagnosed with stroke. Our untargeted and targeted metabolomics approaches support investigating these compounds as novel biomarkers for early and non-invasive detection of thrombotic stroke.

中文翻译：

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对有血栓性中风风险的人的血清进行整体代谢组学分析。

我们旨在确定改变的化合物的血清浓度，以了解血栓性中风之前发生的代谢和病理生理学变化。在这项前瞻性队列研究中，高分辨率代谢组学（HRM）用于分析从有中风风险（n = 99）和无风险对照组（n = 301）的患者那里获得的血清样本。使用偏最小二乘判别分析（PLS-DA），以及使用q = 0.05的错误发现率（FDR）进行单变量分析，来识别判别性代谢谱，并确定健康对照组和中风风险组之间的代谢产物显着不同。PLS-DA令人满意地将中风风险血清与对照血清分开。此外，这些判别性代谢特征与高血压，吸烟，糖尿病，或胰岛素敏感性。使用非靶向代谢组学鉴定了一组35种代谢物，其中大多数是氨基酸，它们能够将中风风险血清与对照区分开。此外，有针对性的代谢组学方法证实，在后来被诊断出的患者血清中，l-色氨酸，3-甲氧基酪胺，蛋氨酸，高半胱氨酸亚磺酸，半胱氨酸，异亮氨酸，肉碱，精氨酸，亚油酸和鞘氨醇的定量浓度特别升高。中风。我们的非靶向和靶向代谢组学方法支持对这些化合物的研究，将其作为血栓性中风的早期和非侵入性检测的新型生物标志物。此外，有针对性的代谢组学方法证实，在后来被诊断出的患者血清中，l-色氨酸，3-甲氧基酪胺，蛋氨酸，高半胱氨酸亚磺酸，半胱氨酸，异亮氨酸，肉碱，精氨酸，亚油酸和鞘氨醇的定量浓度特别升高。中风。我们的非靶向和靶向代谢组学方法支持对这些化合物的研究，将其作为血栓性中风的早期和非侵入性检测的新型生物标志物。此外，有针对性的代谢组学方法证实，在后来被诊断出的患者血清中，l-色氨酸，3-甲氧基酪胺，蛋氨酸，高半胱氨酸亚磺酸，半胱氨酸，异亮氨酸，肉碱，精氨酸，亚油酸和鞘氨醇的定量浓度特别升高。中风。我们的非靶向和靶向代谢组学方法支持对这些化合物的研究，将其作为血栓性中风的早期和非侵入性检测的新型生物标志物。