Background and aims

Nuclear magnetic resonance (NMR)-based metabolomics analyses have defined the lipoprotein profile of carotid artery intima-media thickness (IMT) in detail. In this study, the aim was to use multi-modal mass spectroscopy (MS) to relate multiple metabolites from different chemical classes to IMT and also to the echogenicity of the intima-media complex (IM-GSM).

Method

Multi-modal MS with 791 annotated non-xenobiotic metabolites was measured in two different population-based samples (PIVUS at age 80, n = 586 and POEM at age 50, n = 495) in which also carotid IMT and IM-GSM have been assessed by ultrasound.

Results

Four metabolites were significantly (false discovery rate, FDR<0.05) related to IMT in a meta-analysis of POEM and PIVUS. The top finding was adenosine 3′,5′-cyclic monophosphate (cAMP), being inversely related to IMT. Fifty metabolites were significantly related to IM-GSM in a meta-analysis of POEM and PIVUS. The top findings were branched-chained amino acids (BCAA), fructosyllysine, metabolonic lactone sulfate, a ceramide together with some sphingomyelins and phosphatidylcholines. All these top findings represented inverse relationships. Two metabolites identified by lasso regression in PIVUS increased discrimination of an echolucent IM-GSM by 3.3% in POEM compared to traditional cardiovascular risk factors (p = 0.020).

Conclusions

IMT, especially IM-GSM, was related to multiple metabolites from different chemical classes. Although such metabolites improved the discrimination of an echolucent IM-GSM, it remains to be investigated if any of those metabolites are involved in the pathogenesis of carotid arteriopathy.

中文翻译：

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颈动脉内中膜厚度和回声的代谢组学特征

背景和目标

基于核磁共振 (NMR) 的代谢组学分析详细定义了颈动脉内中膜厚度 (IMT) 的脂蛋白谱。在这项研究中，目的是使用多模态质谱 (MS) 将来自不同化学类别的多种代谢物与 IMT 以及内膜中膜复合物 (IM-GSM) 的回声相关联。

方法

在两种不同的基于人群的样本（80 岁的 PIVUS，n = 586 和 50 岁的 POEM，n = 495）中测量了具有 791 种注释的非异生物代谢物的多模式 MS，其中颈动脉 IMT 和 IM-GSM 也已被测量通过超声评估。

结果

在 POEM 和 PIVUS 的荟萃分析中，四种代谢物与 IMT 显着相关（错误发现率，FDR<0.05）。最重要的发现是腺苷 3',5'-环磷酸腺苷 (cAMP)，与 IMT 呈负相关。在 POEM 和 PIVUS 的荟萃分析中，50 种代谢物与 IM-GSM 显着相关。最重要的发现是支链氨基酸 (BCAA)、果糖基赖氨酸、代谢内酯硫酸盐、神经酰胺以及一些鞘磷脂和磷脂酰胆碱。所有这些最重要的发现都代表了反向关系。与传统的心血管危险因素相比，PIVUS 中通过套索回归确定的两种代谢物使 POEM 中回声透明 IM-GSM 的辨别率提高了 3.3%（p  = 0.020）。

结论

IMT，尤其是 IM-GSM，与来自不同化学类别的多种代谢物有关。尽管这些代谢物提高了对回声 IM-GSM 的辨别力，但这些代谢物是否与颈动脉病的发病机制有关，仍有待研究。