肾功能受损和代谢控制不佳会混淆三甲胺-N-氧化物的血浆水平。

Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control.

作者信息

Mueller Daniel M, Allenspach Martina, Othman Alaa, Saely Christoph H, Muendlein Axel, Vonbank Alexander, Drexel Heinz, von Eckardstein Arnold

机构信息

Institute of Clinical Chemistry, University Hospital and University of Zurich, Zurich, Switzerland.

Institute of Clinical Chemistry, University Hospital and University of Zurich, Zurich, Switzerland; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.

出版信息

Atherosclerosis. 2015 Dec;243(2):638-44. doi: 10.1016/j.atherosclerosis.2015.10.091. Epub 2015 Oct 24.

DOI:10.1016/j.atherosclerosis.2015.10.091

PMID:26554714

Abstract

BACKGROUND

After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.

METHODS

A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.

RESULTS

Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9 μmol/L; p < 0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980 μmol/L; p = 0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43 μmol/L; p = 0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho: -0.281; p < 0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8 μmol/L; p = 0.045).

CONCLUSIONS

Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease.

摘要

背景

摄入磷脂酰胆碱、左旋肉碱或甜菜碱后，肠道微生物群和肝脏酶会形成氧化三甲胺（TMAO）。血浆TMAO水平升高与心血管疾病风险增加及其他疾病有关。近期研究还发现，甜菜碱和胆碱本身也与心血管疾病风险增加有关。

方法

采用新开发的液相色谱-高分辨质谱法（LC-HRMS），对339例因疑似冠状动脉疾病接受冠状动脉造影的患者血浆中的TMAO、甜菜碱和胆碱浓度进行测定。

结果

男性的甜菜碱浓度显著高于女性（42.0 vs. 35.9 μmol/L；p < 0.001）。与血糖正常的患者相比，糖尿病患者的血浆TMAO浓度更高，但甜菜碱和胆碱浓度无差异（2.39 vs. 0.980 μmol/L；p = 0.001）；与无代谢综合征的患者相比，代谢综合征患者的血浆TMAO浓度更高（2.37 vs. 1.43 μmol/L；p = 0.002）。随着肾功能下降，血浆TMAO或胆碱浓度显著升高（斯皮尔曼相关系数：-0.281；p < 0.001）。然而，血浆TMAO或甜菜碱水平与心肌梗死病史、冠状动脉造影评估的冠心病存在情况以及8年随访期间的心血管事件均无关联。有急性心肌梗死病史的患者血浆胆碱水平显著低于无此病史的患者（10.0 vs. 10.8 μmol/L；p = 0.045）。