Li Xinmin S, Obeid Slayman, Klingenberg Roland, Gencer Baris, Mach François, Räber Lorenz, Windecker Stephan, Rodondi Nicolas, Nanchen David, Muller Olivier, Miranda Melroy X, Matter Christian M, Wu Yuping, Li Lin, Wang Zeneng, Alamri Hassan S, Gogonea Valentin, Chung Yoon-Mi, Tang W H Wilson, Hazen Stanley L, Lüscher Thomas F
Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland.
Eur Heart J. 2017 Mar 14;38(11):814-824. doi: 10.1093/eurheartj/ehw582.
Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown.
We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts. In the Cleveland Cohort, comprised of sequential subjects (n = 530) presenting to the Emergency Department (ED) with chest pain of suspected cardiac origin, an elevated plasma TMAO level at presentation was independently associated with risk of major adverse cardiac events (MACE, including myocardial infarction, stroke, need for revascularization, or death) over the ensuing 30-day (4th quartile (Q4) adjusted odds ratio (OR) 6.30, 95% confidence interval (CI), 1.89-21.0, P < 0.01) and 6-month (Q4 adjusted OR 5.65, 95%CI, 1.91-16.7; P < 0.01) intervals. TMAO levels were also a significant predictor of the long term (7-year) mortality (Q4 adjusted HR 1.81, 95%CI, 1.04-3.15; P < 0.05). Interestingly, TMAO level at initial presentation predicted risk of incident MACE over the near-term (30 days and 6 months) even among subjects who were initially negative for troponin T (< 0.1 ng/mL) (30 days, Q4 adjusted OR 5.83, 95%CI, 1.79-19.03; P < 0.01). The prognostic value of TMAO was also assessed in an independent multicentre Swiss Cohort of ACS patients (n = 1683) who underwent coronary angiography. Trimethylamine N-oxide again predicted enhanced MACE risk (1-year) (adjusted Q4 hazard ratios: 1.57, 95% CI, 1.03-2.41; P <0.05).
Plasma TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events, and may thus provide clinical utility in risk stratification among subjects presenting with suspected ACS.
氧化三甲胺（TMAO）是一种由肠道微生物群对含三甲胺（TMA）的膳食营养素（如胆碱或肉碱）进行代谢产生的促动脉粥样硬化和促血栓形成代谢物，其全身水平可预测稳定的一级和二级预防患者发生心血管事件的风险。然而，TMAO在急性冠状动脉综合征（ACS）中的预后价值仍不清楚。
我们在两个独立队列中研究了TMAO水平与ACS连续患者发生心血管风险之间的关系。在克利夫兰队列中，由因疑似心脏源性胸痛就诊于急诊科（ED）的连续受试者（n = 530）组成，就诊时血浆TMAO水平升高与随后30天（第四四分位数（Q4）调整优势比（OR）6.30，95%置信区间（CI），1.89 - 21.0，P < 0.01）和6个月（Q4调整OR 5.65，95%CI，1.91 - 16.7；P < 0.01）期间发生主要不良心脏事件（MACE，包括心肌梗死、中风、血管重建需求或死亡）的风险独立相关。TMAO水平也是长期（7年）死亡率的显著预测因子（Q4调整风险比1.81，95%CI，1.04 - 3.15；P < 0.05）。有趣的是，即使在最初肌钙蛋白T阴性（< 0.1 ng/mL）的受试者中，初始就诊时的TMAO水平也能预测近期（30天和6个月）发生MACE的风险（30天，Q4调整OR 5.83，95%CI，1.79 - 19.03；P < 0.01）。还在一个接受冠状动脉造影的独立多中心瑞士ACS患者队列（n = 1683）中评估了TMAO的预后价值。氧化三甲胺再次预测MACE风险增加（1年）（调整后的Q4风险比：1.57，95%CI，1.03 - 2.41；P < 0.05）。
胸痛患者的血浆TMAO水平可预测心血管事件发生的近期和长期风险，因此可能在疑似ACS患者的风险分层中提供临床应用价值。
