作者：韩嘉明，段豪亮，刘杏利，马玉兰

单位：

1.青海大学医学院2.青海大学附属医院心血管内科

Units：

1.Medical College of Qinghai University, Xining 810000, China 2.Department of Cardiology, Affiliated Hospital of Qinghai University, Xining 810000, China

关键词：

心力衰竭; 氧化三甲胺; 全因死亡; 主要不良心血管事件; Meta分析; 剂量-反应关系;

Keywords：

Heart failure; Trimethylamine-N-oxide; All-cause mortality; Major adverse cardiovascular events; Metaanalysis; Dose-response analysis

CLC：

DOI：

10.12114/j.issn.1008-5971.2023.00.062

Funds：

国家自然科学基金地区科学基金项目（81760084）；

摘要：

目的 系统评价血浆氧化三甲胺（TMAO）水平与心力衰竭患者预后[全因死亡和主要不良心血管事件（MACE）]的关系，并分析血浆TMAO水平与心力衰竭患者发生全因死亡风险的剂量-反应关系。方法 计算机检索中国知网、万方数据知识服务平台、超星数字图书馆、维普网、Cochrane Library、Web of Science、PubMed、Embase等公开发表的血浆TMAO水平与心力衰竭患者全因死亡和MACE关系的前瞻性队列研究。检索时限从建库至2022年12月。提取纳入文献的资料，采用纽卡斯尔-渥太华量表（NOS）进行文献质量评价，采用Stata 17.0软件进行Meta分析及剂量-反应关系分析。结果 共纳入13篇文献17项研究及11 260例患者。Meta分析结果显示，血浆TMAO水平是心力衰竭患者发生全因死亡的影响因素[HR=1.38,95%CI(1.24,1.53)]；亚组分析结果显示，随访时间<3年和随访时间≥3年的研究均显示血浆TMAO水平是心力衰竭患者发生全因死亡的影响因素[HR=1.22,95%CI(1.13,1.33);HR=1.66,95%CI(1.46,1.89)]。血浆TMAO水平是心力衰竭患者发生MACE的影响因素[HR=1.35,95%CI(1.18,1.55)]；亚组分析结果显示，随访时间<3年和随访时间≥3年的研究均显示血浆TMAO水平是心力衰竭患者发生MACE的影响因素[HR=1.25,95%CI(1.12,1.41);HR=1.53,95%CI(1.05,2.25)]。剂量-反应关系分析结果显示，血浆TMAO水平与心力衰竭患者发生全因死亡的风险呈线性剂量-反应关系，血浆TMAO水平每升高1μmol/L，全因死亡发生风险增加4.8%。结论 血浆TMAO水平是心力衰竭患者发生全因死亡和MACE的影响因素，血浆TMAO水平每升高1μmol/L，心力衰竭患者全因死亡发生风险增加4.8%。

Abstract：

　Objective To systematically evaluate the relationship between plasma trimethylamine N-oxide (TMAO) level and prognosis [all-cause death and major adverse cardiovascular events (MACE) ] in patients with heart failure, and analyze the dose-response relationship between plasma TMAO level and risk of all-cause death in patients with heart failure. Methods Databases including CNKI, Wanfang Data, Superstar Digital Library, VIP, Cochrane Library, Web of Science, PubMed, Embase were searched for prospective cohort studies on the relationship between plasma TMAO level and all-cause death and MACE in patients with heart failure from inception to December 2022. The data of the included literature were extracted, the NewcastleOttawa Scale (NOS) was used to evaluate the quality of the included literature, and Stata 17.0 was used for meta-analysis and dose-response relationship analysis. Results A total of 13 articles and 17 studies were included, and involving 11 260 patients. Meta-analysis results showed that plasma TMAO level was an influencing factor of all-cause death in patients with heart failure [HR=1.38, 95%CI (1.24, 1.53) ] . The results of subgroup analysis showed that, studies with a follow-up period of less than 3 years and a follow-up period greater than or equal to 3 years both showed that plasma TMAO level was an influencing factor of all-cause death in patients with heart failure [HR=1.22, 95%CI (1.13, 1.33) ; HR=1.66, 95%CI (1.46, 1.89) ] . Plasma TMAO level was an influencing factor of MACE in patients with heart failure [HR=1.35, 95%CI (1.18, 1.55) ] . The results of subgroup analysis showed that, studies with a follow-up period of less than 3 years and a follow-up period greater than or equal to 3 years both showed that plasma TMAO level was an influencing factor of MACE in patients with heart failure [HR=1.25, 95%CI (1.12, 1.41) ; HR=1.53, 95%CI (1.05, 2.25) ] . Dose-response relationship analysis results showed that there was a linear dose-response relationship between plasma TMAO level and the risk of all-cause death in patients with heart failure, for every 1 μmol/L increase in plasma TMAO level, the risk of all-cause mortality increased by 4.8%. Conclusion Plasma TMAO level is an influencing factor of allcause death and MACE in patients with heart failure, for every 1 μmol/L increase in plasma TMAO level, the risk of all-cause mortality increases by 4.8%.

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