肠道相关代谢物与急性心力衰竭预后的关系。

Association of gut-related metabolites with outcome in acute heart failure.

机构信息

Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom.

IRCCS SDN, Diagnostic and Nuclear Research Institute, Naples, Italy.

出版信息

Am Heart J. 2021 Apr;234:71-80. doi: 10.1016/j.ahj.2021.01.006. Epub 2021 Jan 14.

DOI:10.1016/j.ahj.2021.01.006

PMID:33454370

Abstract

BACKGROUND

Trimethylamine N-oxide (TMAO), a gut-related metabolite, is associated with heart failure (HF) outcomes. However, TMAO is the final product of a complex metabolic pathway (ie, choline/carnitine) that has never been entirely investigated in HF. The present study investigates a panel of metabolites involved in the TMAO-choline/carnitine metabolic pathway for their associations with outcome in acute HF patients.

METHODS

In total, 806 plasma samples from acute HF patients were analyzed for TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, γ-butyrobetaine, crotonobetaine, trimethylamine, betaine aldehyde, choline, and betaine using a developed liquid chromatography-tandem mass spectrometry method. Associations with outcome of all-cause mortality (death) and a composite of all-cause mortality and/or rehospitalization caused by HF (death/HF) at 30 days and 1 year were investigated.

RESULTS

TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, and γ-butyrobetaine were associated with death and death/HF at 30 days (short term; hazard ratio 1.30-1.49, P≤ .021) and at 1 year (long term; hazard ratio 1.15-1.25, P≤ .026) when adjusted for cardiac risk factors. L-carnitine and acetyl-L-carnitine were superior for short-term outcomes whereas TMAO was the superior metabolite for association with long-term outcomes. Furthermore, acetyl-L-carnitine and L-carnitine were superior for in-hospital mortality and improved risk stratification when combined with current clinical risk scores (ie, Acute Decompensated HEart Failure National REgistry, Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure, and Get With The Guidelines-Heart Failure; odds ratio (OR) ≥ 1.52, P≤ .020).

CONCLUSIONS

Carnitine-related metabolites show associations with adverse outcomes in acute HF, in particular L-carnitine and acetyl-L-carnitine for short-term outcomes, and TMAO for long-term outcomes. Further studies are warranted to investigate the role and implications of carnitine metabolites including intervention in the pathogenesis of HF.

摘要

背景

三甲胺 N-氧化物（TMAO）是一种与心力衰竭（HF）结局相关的肠道相关代谢物。然而，TMAO 是一个复杂代谢途径（即胆碱/肉碱）的最终产物，该途径从未在 HF 中完全研究过。本研究调查了 TMAO-胆碱/肉碱代谢途径中一组参与的代谢物与急性 HF 患者结局的相关性。

方法

总共分析了 806 例急性 HF 患者的血浆样本，使用开发的液相色谱-串联质谱法检测 TMAO、三甲基赖氨酸、左旋肉碱、乙酰左旋肉碱、γ-丁酰甜菜碱、丁烯酸甜菜碱、三甲胺、甜菜碱醛、胆碱和甜菜碱。研究了所有原因死亡率（死亡）和所有原因死亡率和/或 HF 再住院的复合终点（30 天和 1 年时的死亡/HF）与所有结果的相关性。

结果

TMAO、三甲基赖氨酸、左旋肉碱、乙酰左旋肉碱和 γ-丁酰甜菜碱与 30 天（短期）和 1 年（长期）时的死亡和死亡/HF 相关（危险比 1.30-1.49，P≤.021），调整心脏危险因素后。左旋肉碱和乙酰左旋肉碱与短期结局相关，而 TMAO 与长期结局相关。此外，乙酰左旋肉碱和左旋肉碱在与当前临床风险评分（即急性失代偿性心力衰竭国家登记处、医院心力衰竭患者救生治疗组织计划和 Get With The Guidelines-心力衰竭）联合使用时对住院死亡率和改善风险分层更有优势（优势比（OR）≥1.52，P≤.020）。