Metabolomic Factors Associated With Major Adverse Cardiovascular Events in Patients With Coronary Heart Disease: A Systematic Review and Meta-Analysis

Abstract

Purpose. To synthesize metabolomic factors associated with major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD). Methods. PubMed, Embase, Web of Science, Scopus, the Cochrane Library, CNKI, Wanfang, and VIP were systematically searched from database inception to June 2026, with no language restrictions. Two reviewers independently screened studies and extracted data. Data were analyzed using Stata/MP 17; study quality was assessed using the Newcastle–Ottawa Scale (NOS); and sensitivity analyses, publication-bias assessment, and GRADE certainty assessment were performed when applicable. Results. A total of 17 studies were included, of which 7 studies contributed to at least one meta-analysis, while the remaining studies were summarized descriptively. Meta-analysis showed that higher TMAO levels (pooled HR = 1.70, 95% CI: 1.45–2.00) and higher TML levels (pooled HR = 2.03, 95% CI: 1.19–3.44) were associated with increased MACE risk. Choline, betaine, and L-carnitine were not significantly associated with MACE in meta-analyses. Descriptive findings suggested that dimethylglycine, phenylacetylglutamine, indoxyl sulfate, deoxycholic acid, acetylcarnitine, butyrylcarnitine, selected ceramide species, homocysteine, and phenylalanine were associated with higher risk of MACE or adverse cardiovascular outcomes, whereas tryptophan and fumarate showed inverse associations in individual studies. Conclusions. Metabolomic findings, particularly TMAO-related findings, are associated with MACE risk in patients with CHD. These findings may help characterize residual cardiovascular risk and support future individualized secondary prevention and nursing follow-up. PROSPERO registration:CRD420251183805.