Abstract 13681: Association of Serum Trimethylamine N-oxide Levels With Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Background: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite of red meat, has emerged as a potential biomarker for CVD and all-cause mortality. It is also found in preformed amounts in fish. However, the association between serum TMAO levels and CVD outcomes remain unclear.

Aim: To conduct a systematic review and dose-response meta-analysis evaluating the association between serum TMAO and CVD and all-cause mortality in prospective cohort studies.

Methods: A comprehensive literature search was conducted in MEDLINE, EMBASE, and Cochrane Library up to and including March 6, 2023. A manual search through references found in reviews and meta-analyses was also conducted. Studies reporting hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs) for the association between serum TMAO levels and CVD or all-cause mortality in adults ≥ 18 years with follow-up of ≥ 1 year were included. Random-effects models were utilized for pooled risk estimates and assess the dose-response. GRADE was used to evaluate certainty of evidence.

Results: 2459 papers, 44 prospective cohort studies were included involving 84771 participants included in final analysis (fig.1). Pooled analyses revealed a significant positive association between elevated serum TMAO levels and the risk of total CVD (RR 1.29 [1.16-1.44]), CVD mortality (RR 1.51 [1.23-1.87]) and all-cause mortality (RR 1.30 [1.21,1.39]). Non-significant associations were found for MI, stroke, total CHD, MI mortality and CHD mortality. All outcomes were of low to very low certainty.Dose response analysis revealed a significant linear association with all-cause mortality (RR 1.01 [95% CI 1.01, 1.02] per 2μM/L) up to a threshold of 6μM/L and total CVD (RR 1.04 [1.02-1.06]).

Conclusion: This study provides evidence supporting the positive association of serum TMAO levels with increased risk of total CVD, CVD mortality and all-cause mortality. A recent review found 13/15 studies demonstrated a strong positive correlation between TMAO and fish intake, complicating the hypotheses relating TMAO in red meat and CVD risk. Thus, further assessments of diet components are needed to explore the clinical implications of the associations found in our study.