Background and aims

The association of plasma trimethylamine N-oxide (TMAO) with atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus (DM) and its determinants, as well as the role of TMAO as a predictor for short and long-term mortality, is still under discussion. We investigated associations between four plasma metabolites of the TMAO pathway and different clinical manifestations of atherosclerosis, diabetes determinants, and risk of short and long-term mortality in patients with stable ASCVD, acute myocardial infarction (AMI), cardiogenic shock (CS), and DM in three independent cohorts.

Methods

TMAO and its dietary precursors were simultaneously quantified by liquid chromatography-tandem mass spectrometry in a total of 2655 participants of the German Leipzig Research Center for Civilization Diseases (LIFE)-Heart study, LIFE-Adult study, and the European Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) multicenter trial. Associations with ASCVD manifestations, metabolic syndrome, 30-day mortality of patients with AMI and CS, and long-term mortality of subjects with suspected coronary artery disease (CAD) were analyzed.

Results

TMAO plasma levels were not independently associated with stable ASCVD. Elevated TMAO plasma concentrations were independently associated with obesity (odds ratio, 1.23; p < 0.01) and DM (odds ratio, 1.37; p < 0.001) in LIFE-Heart. The latter association was confirmed in LIFE-Adult. We found no association of TMAO plasma levels with short-term mortality in patients with AMI and CS. However, TMAO plasma levels were independent predictors of long-term mortality in patients with suspected CAD (hazard ratio, 1.24; p < 0.05).

Conclusions

Potential proatherogenic mechanisms of TMAO seem to have no short-term effect in AMI. Presented associations with diabetes mellitus and obesity suggest that TMAO might have a functional role in metabolic syndrome.

中文翻译：

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血浆三甲胺N-氧化物水平与动脉粥样硬化性心血管疾病和代谢综合征因素的关系

背景和目标

血浆三甲胺N-氧化物 (TMAO) 与动脉粥样硬化性心血管疾病 (ASCVD)、糖尿病 (DM) 及其决定因素的关联，以及 TMAO 作为短期和长期死亡率预测因子的作用仍在讨论中. 我们研究了 TMAO 途径的四种血浆代谢物与动脉粥样硬化的不同临床表现、糖尿病决定因素以及稳定性 ASCVD、急性心肌梗死 (AMI)、心源性休克 (CS) 和短期和长期死亡风险之间的关联。 DM 在三个独立的队列中。

方法

在德国莱比锡文明疾病研究中心 (LIFE)-心脏研究、LIFE-成人研究和欧洲仅罪犯病变 PCI与欧洲罪犯病变研究中心 (LIFE) 的总共 2655 名参与者中，TMAO 及其膳食前体同时通过液相色谱-串联质谱法进行量化心源性休克中的多支血管 PCI (CULPRIT-SHOCK) 多中心试验。分析了与 ASCVD 表现、代谢综合征、AMI 和 CS 患者 30 天死亡率以及疑似冠状动脉疾病 (CAD) 受试者长期死亡率的关联。

结果

TMAO 血浆水平与稳定的 ASCVD 不独立相关。 在 LIFE-Heart 中 ，TMAO 血浆浓度升高与肥胖（比值比，1.23；p < 0.01）和糖尿病（比值比，1.37；p < 0.001）独立相关。后一种关联在 LIFE-Adult 中得到证实。我们发现 AMI 和 CS 患者的 TMAO 血浆水平与短期死亡率没有关联。然而，TMAO 血浆水平是疑似 CAD 患者长期死亡率的独立预测因子（风险比，1.24；p  < 0.05）。

结论

TMAO 的潜在促动脉粥样硬化机制似乎对 AMI 没有短期影响。与糖尿病和肥胖症的相关性表明 TMAO 可能在代谢综合征中具有功能性作用。