慢性收缩性心力衰竭中肠道微生物群依赖性磷脂酰胆碱代谢产物、舒张功能障碍及不良临床结局
Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure.
作者信息
Tang W H Wilson, Wang Zeneng, Shrestha Kevin, Borowski Allen G, Wu Yuping, Troughton Richard W, Klein Allan L, Hazen Stanley L
机构信息
Center for Cardiovascular Diagnostics and Prevention, Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland, Ohio; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
Center for Cardiovascular Diagnostics and Prevention, Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland, Ohio.
出版信息
J Card Fail. 2015 Feb;21(2):91-6. doi: 10.1016/j.cardfail.2014.11.006. Epub 2014 Nov 20.
BACKGROUND
Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aimed to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF).
METHODS AND RESULTS
In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median (interquartile range) TMAO levels, choline, and betaine levels were 5.8 (3.6-12.1) μmol/L, 10.9 (8.4-14.0) μmol/L, and 43.8 (37.1-53.0) μmol/L, respectively, and were correlated with each other (all P < .0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9-13.2] vs 4.8 [3.4-9.8] μmol/L; P = .005) and in subjects with New York Heart Association functional class III or greater (7.0 [4.7-14.8] vs 4.7 [3.4-11.3] μmol/L; P = .02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (hazard ratio [HR] 1.64, 95% CI 1.22-2.20; P = .001), betaine (HR 1.51, 95% CI 1.10-2.08; P = .01), and TMAO (HR 1.48, 95% CI 1.10-1.96; P = .01) predicted increased risk for 5-year adverse clinical events (death/transplantation). Only higher TMAO levels predicted incident adverse clinical events independently from age, estimated glomerular filtration rate, mitral E/septal Ea, and NT-proBNP levels (HR 1.46, 95% CI 1.03-2.14; P = .03).
CONCLUSION
Elevated plasma TMAO, choline, and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO was associated with poor prognosis after adjustment for cardiorenal indices.
背景
氧化三甲胺（TMAO）与心血管疾病风险增加有关。我们旨在确定TMAO及其膳食前体胆碱和甜菜碱在心力衰竭（HF）中的预后价值。
方法和结果
在112例接受全面超声心动图评估的慢性收缩性HF患者中，我们通过质谱法测量了血浆TMAO、胆碱和甜菜碱。TMAO水平、胆碱水平和甜菜碱水平的中位数（四分位间距）分别为5.8（3.6 - 12.1）μmol/L、10.9（8.4 - 14.0）μmol/L和43.8（37.1 - 53.0）μmol/L，且彼此相关（两者均P <.0001）。糖尿病患者的TMAO水平显著更高（9.4 [4.9 - 13.2] vs 4.8 [3.4 - 9.8] μmol/L；P =.005），纽约心脏协会功能分级为III级或更高的受试者也是如此（7.0 [4.7 - 14.8] vs 4.7 [3.4 - 11.3] μmol/L；P =.02）。TMAO、胆碱和甜菜碱水平升高均与较高的血浆N末端B型利钠肽原（NT - proBNP）水平以及更严重的左心室舒张功能障碍相关，但与收缩功能障碍或炎症及内皮生物标志物无关。较高的胆碱（风险比[HR] 1.64，95%置信区间1.22 - 2.20；P =.001）、甜菜碱（HR 1.51，95%置信区间1.10 - 2.08；P =.01）和TMAO（HR 1.48，95%置信区间1.10 - 1.96；P =.01）预测5年不良临床事件（死亡/移植）风险增加。只有较高的TMAO水平独立于年龄、估计肾小球滤过率、二尖瓣E/室间隔Ea和NT - proBNP水平预测不良临床事件的发生（HR 1.46，95%置信区间1.03 - 2.14；P =.03）。
结论
血浆TMAO、胆碱和甜菜碱水平升高均与更严重的左心室舒张功能障碍相关，并预示慢性收缩性HF患者长期不良临床结局更差。然而，在调整心肾指标后，只有较高的血浆TMAO与不良预后相关。
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