Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies.
Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies.
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DOI：
10.1161/jaha.116.004947
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发表时间：
2017-06-29
影响因子：
5.4
通讯作者：
Qi L
中科院分区：
文献类型：
--
作者：
Heianza Y;Ma W;Manson JE;Rexrode KM;Qi L
肠道微生物代谢物已被认为是心血管事件和过早死亡的新危险因素。肠道微生物代谢物三甲胺氧化氮（TMAO）及其前体血液浓度与主要不良心血管事件（MACE）或死亡之间的关联强度和一致性尚未得到全面评估。我们量化了TMAO及其前体血液浓度与MACE风险和死亡率的关系。检索PubMed和Embase数据库，我们的主要分析共纳入了来自16篇出版物的19项前瞻性研究（n=19 256，包括3315例事件病例），这些研究定量估计了TMAO与MACE发展或死亡的关系。当这些指标可用时，使用多变量调整相对风险（RRs）。与低TMAO水平相比，TMAO浓度升高与MACE的合并RR为1.62 （95% CI, 1.45, 1.80； P异质性=0.2;I2=23.5%）相关，1项针对黑人参与者的研究影响了该关联的异质性。在排除黑人数据后，根据体重指数、糖尿病患病率、心血管病史和肾功能障碍，rr无差异。此外，TMAO浓度升高与全因死亡率的总风险比为1.63（1.36,1.95）。TMAO前体（l -肉毒碱、胆碱或甜菜碱）浓度升高的个体发生MACE的风险约为低浓度个体的1.3至1.4倍。TMAO及其前体浓度升高与MACE风险增加和全因死亡率相关，独立于传统危险因素。
Gut microbial metabolites have been implicated as novel risk factors for cardiovascular events and premature death. The strength and consistency of associations between blood concentrations of the gut microbial metabolites, trimethylamine‐N‐oxide (TMAO) and its precursors, with major adverse cardiovascular events (MACE) or death have not been comprehensively assessed. We quantified associations of blood concentrations of TMAO and its precursors with risks of MACE and mortality. PubMed and Embase databases were searched up, and a total of 19 prospective studies from 16 publications (n=19 256, including 3315 incident cases) with quantitative estimates of the associations of TMAO with the development of MACE or death were included in our main analysis. Multivariate‐adjusted relative risks (RRs) were used when these were available. Elevated concentrations of TMAO were associated with a pooled RR of 1.62 (95% CI, 1.45, 1.80; P heterogeneity=0.2; I2=23.5%) for MACE compared with low TMAO levels, and 1 study of black participants influenced the heterogeneity of the association. After excluding the data of blacks, the RRs were not different according to body mass index, prevalence of diabetes mellitus, history of cardiovascular diseases, and kidney dysfunction. Furthermore, elevated TMAO concentrations were associated with a pooled RR of 1.63 (1.36, 1.95) for all‐cause mortality. Individuals with elevated concentrations of TMAO precursors (l‐carnitine, choline, or betaine) had an approximately 1.3 to 1.4 times higher risk for MACE compared to those with low concentrations. Elevated concentrations of TMAO and its precursors were associated with increased risks of MACE and all‐cause mortality independently of traditional risk factors.