Trimethyllysine, a trimethylamine N-oxide precursor, provides near- and long-term prognostic value in patients presenting with acute coronary syndromes
Trimethyllysine, a trimethylamine N-oxide precursor, provides near- and long-term prognostic value in patients presenting with acute coronary syndromes
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DOI：
10.1093/eurheartj/ehz259
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发表时间：
2019-08-21
影响因子：
39.3
通讯作者：
Hazen, Stanley L.
中科院分区：
文献类型：
--
作者：
Li, Xinmin S.;Obeid, Slayman;Hazen, Stanley L.
目的 三甲基赖氨酸 (TML) 是肠道微生物群衍生代谢物三甲胺 N-氧化物 (TMAO) 的营养前体，与稳定受试者的心血管 (CV) 事件相关。我们检查了急性冠脉综合征 (ACS) 患者血浆 TML 水平与心血管事件之间的关系。方法和结果使用质谱法对两个独立队列中的血浆 TML 水平进行了定量，并研究了其与 CV 事件的关系。在克利夫兰队列 (N= 530) 中，由因胸痛和疑似 ACS 到急诊科就诊的患者组成，TML 与 30 天内的主要不良心脏事件（MACE、心肌梗死、中风、需要血运重建或全因死亡）相关[第三个三分位数 (T3)，调整后比值比 (OR) 1.77，95% 置信区间 (CI) 1.04-3.01； P < 0.05] 和 6 个月（T3，调整 OR 1.95，95% CI 1.15-3.32；P < 0.05）的随访，独立于传统的 CV 危险因素和肾功能指标。 TML 水平升高还与长期（7 年）全因死亡率相关[T3，调整后风险比 (HR) 2.52，95% CI 1.50-4.24； P < 0.001]，甚至在就诊时心肌肌钙蛋白 T 持续阴性的患者中也存在 MACE（例如 30 天 MACE，T3，调整后 OR 4.49，95% CI 2.06-9.79；P < 0.001）。三甲基赖氨酸与 TMAO 联合使用对近期和长期 CV 事件（包括高敏肌钙蛋白 T 水平“阴性”的患者）显示出额外的意义。在由 ACS 患者组成的多中心瑞士队列 (N= 1683) 中，观察到 TML 与事件 1 年不良心脏风险之间存在类似关联（例如死亡率，调整后 T3 HR 2.74，95% CI 1.28-5.85；P < 0.05；MACE，调整后 T3 HR 1.55，95% CI 1.04-2.31；P < 0.05）。结论 血浆 TML 水平（单独或与 TMAO 一起）与胸痛和 ACS 患者的近期和长期 CV 事件相关。
Aims Trimethyllysine (TML) serves as a nutrient precursor of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) and is associated with incident cardiovascular (CV) events in stable subjects. We examined the relationship between plasma TML levels and incident CV events in patients presenting with acute coronary syndromes (ACS).Methods and results Plasma levels of TML were quantified in two independent cohorts using mass spectrometry, and its relationship with CV events was investigated. In a Cleveland Cohort (N= 530), comprised of patients presenting to the emergency department with chest pain and suspected ACS, TML was associated with major adverse cardiac events (MACE, myocardial infarction, stroke, need for revascularization, or all-cause mortality) over both 30 days [3rd tertile (T3), adjusted odds ratio (OR) 1.77, 95% confidence interval (CI) 1.04-3.01; P < 0.05] and 6 months (T3, adjusted OR 1.95, 95% CI 1.15-3.32; P < 0.05) of follow-up independent of traditional CV risk factors and indices of renal function. Elevated TML levels were also associated with incident long-term (7-year) all-cause mortality [T3, adjusted hazard ratio (HR) 2.52, 95% CI 1.50-4.24; P < 0.001], and MACE even amongst patients persistently negative for cardiac Troponin T at presentation (e.g. 30-day MACE, T3, adjusted OR 4.49, 95% CI 2.06-9.79; P < 0.001). Trimethyllysine in combination with TMAO showed additive significance for near- and long-term CV events, including patients with `negative' high-sensitivity Troponin T levels. In a multicentre Swiss Cohort (N= 1683) comprised of ACS patients, similar associations between TML and incident 1-year adverse cardiac risks were observed (e.g. mortality, adjusted T3 HR 2.74, 95% CI 1.28-5.85; P < 0.05; and MACE, adjusted T3 HR 1.55, 95% CI 1.04-2.31; P < 0.05).Conclusion Plasma TML levels, alone and together with TMAO, are associated with both near- and long-term CV events in patients with chest pain and ACS.