Zhang Chunyu, He Jinyu, Huo Yujia, Liu Lin, Xie Yong, Meng Yufei, Wei Gang, Deng Li, Jiang Yang, Feng Jian
Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Department of Cardiology, Hejiang County People's Hospital, Luzhou, Sichuan, China.
Nutr J. 2025 Jun 16;24(1):91. doi: 10.1186/s12937-025-01159-9.
Cardiovascular diseases are the leading cause of mortality worldwide, with acute coronary syndrome (ACS) being particularly fatal. Percutaneous coronary intervention (PCI) is a key treatment for ACS; however, major adverse cardiovascular events (MACE) frequently occur postoperatively. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been proposed as an emerging risk factor for cardiovascular disease. This study aims to systematically evaluate TMAO's predictive value for MACE post-PCI and explore its dose-response relationship.
A comprehensive literature search was conducted in four databases (PubMed, Web of Science, Embase, and the Cochrane Library), including retrospective or prospective cohort studies involving patients undergoing PCI. The primary outcome was MACE, and the secondary outcome was all-cause mortality. A dose-response analysis was conducted using a restricted cubic spline model to explore potential nonlinear associations between TMAO levels and outcomes. Heterogeneity was assessed using the Cochrane Q test and the I² statistic. Subgroup analysis and meta-regression were performed to identify sources of heterogeneity.
Eleven studies (comprising 13 independent cohorts) with 11,279 participants were included. Pooled analysis showed a significant association between elevated plasma TMAO levels and an increased risk of MACE after PCI (HR: 1.99, 95%CI: 1.68-2.35, 95%PI: 1.64-2.40, I² = 0%, p < 0.00001). Similarly, elevated plasma TMAO levels were significantly associated with an increased risk of all-cause mortality after PCI (HR: 1.76, 95%CI: 1.32-2.35, 95%PI: 0.79-3.90, I² = 65.1%, p < 0.00001). The dose-response analysis did not reveal a nonlinear relationship between TMAO and MACE or all-cause mortality. The linear model showed that each 1 µmol/L increase in plasma TMAO was associated with an 8.95% increased hazard of MACE (HR = 1.0895, 95%CI: 1.03-1.15), while all-cause mortality increased by 4% (HR = 1.04, 95%CI: 0.99-1.09).
This study demonstrates that elevated plasma TMAO levels are significantly associated with an increased risk of MACE and all-cause mortality after PCI, with a dose-dependent effect on MACE risk. As a potential biomarker, TMAO may be used to predict the risk of adverse cardiovascular events after PCI, and future studies should further validate its clinical utility.
PROSPERO CRD42024557486.
心血管疾病是全球死亡的主要原因，急性冠状动脉综合征（ACS）尤为致命。经皮冠状动脉介入治疗（PCI）是ACS的关键治疗方法；然而，主要不良心血管事件（MACE）在术后经常发生。氧化三甲胺（TMAO）是一种由肠道微生物群衍生的代谢产物，已被提出作为心血管疾病的新兴危险因素。本研究旨在系统评价TMAO对PCI术后MACE的预测价值，并探讨其剂量反应关系。
在四个数据库（PubMed、Web of Science、Embase和Cochrane图书馆）中进行了全面的文献检索，包括涉及接受PCI患者的回顾性或前瞻性队列研究。主要结局是MACE，次要结局是全因死亡率。使用受限立方样条模型进行剂量反应分析，以探讨TMAO水平与结局之间的潜在非线性关联。使用Cochrane Q检验和I²统计量评估异质性。进行亚组分析和meta回归以确定异质性来源。
纳入了11项研究（包括13个独立队列），共11279名参与者。汇总分析显示，PCI术后血浆TMAO水平升高与MACE风险增加之间存在显著关联（HR：1.99，95%CI：1.68 - 2.35，95%PI：1.64 - 2.40，I² = 0%，p < 0.00001）。同样，PCI术后血浆TMAO水平升高与全因死亡率风险增加显著相关（HR：1.76，95%CI：1.32 - 2.35，95%PI：0.79 - 3.90，I² = 65.1%，p < 0.00001）。剂量反应分析未揭示TMAO与MACE或全因死亡率之间的非线性关系。线性模型显示，血浆TMAO每增加1 μmol/L，MACE风险增加8.95%（HR = 1.0895，95%CI：1.03 - 1.15），而全因死亡率增加4%（HR = 1.04，95%CI：0.99 - 1.09）。
本研究表明，血浆TMAO水平升高与PCI术后MACE风险和全因死亡率增加显著相关，对MACE风险有剂量依赖性影响。作为一种潜在的生物标志物，TMAO可用于预测PCI术后不良心血管事件的风险，未来研究应进一步验证其临床实用性。
PROSPERO CRD42024557486。
