Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide
Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide
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DOI：
10.1093/eurheartj/ehu002
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发表时间：
2014-04-01
影响因子：
39.3
通讯作者：
Hazen, Stanley L.
中科院分区：
文献类型：
--
作者：
Wang, Zeneng;Tang, W. H. Wilson;Hazen, Stanley L.
最近的代谢组学和动物模型研究表明，三甲胺-N-氧化物(TMAO)是一种肠道微生物区系依赖的代谢物，由饮食中含有三甲胺的营养物质如磷脂酰胆碱(PC)、胆碱和肉碱形成，与冠状动脉疾病的发病有关。通过对3903例接受择期冠状动脉造影术的稳定性患者进行为期3年的随访，研究空腹血浆胆碱和甜菜碱水平与主要不良心脏事件(MACE死亡、心肌梗死、卒中)风险之间的关系，旨在探讨全身胆碱和甜菜碱水平对稳定性心脏病患者预后的影响。在我们的研究队列中，TMAO、胆碱和甜菜碱水平的中位数分别为3.7(2.46.2)M、9.8(7.912.2)M和41.1(32.552.1)M。TMAO与胆碱之间的相关性不大，但有统计学意义(r0.33，P 0.001)，而与甜菜碱之间的相关性较小(r0.09，P 0.001)。血浆胆碱和甜菜碱水平越高，患MACE的风险分别增加1.9倍和1.4倍(四分位数分别为1分位数和1分位数；P0.01)。在调整了传统心血管危险因素和高敏C反应蛋白后，胆碱水平升高[1.34(1.031.74)，P<0.05]和甜菜碱水平[1.33(1.031.73)，P<0.05]均预示着MACE风险增加。当TMAO被添加到调整模型中时，胆碱和甜菜碱都不能预测MACE的风险，只有当TMAO升高时，胆碱和甜菜碱才能预测MACE的未来风险。血浆胆碱和甜菜碱水平升高都与独立于传统危险因素的事件MACE风险相关。然而，高胆碱和甜菜碱水平只与未来MACE的高风险相关，并伴随TMAO的增加。
Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients.We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.46.2)M, 9.8 (7.912.2)M, and 41.1 (32.552.1)M, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r 0.33, P 0.001) and less between TMAO and betaine (r 0.09, P 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.031.74), P 0.05], and betaine levels [1.33 (1.031.73), P 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated.Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.