High levels of gut microbiome-generated TMAO associated with CV events and mortality
Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysisLiterature - Schiattarella GG, Sannino A, Toscano E et al. - Eur Heart J ehx342. DOI: https://doi.org/10.1093/eurheartj/ehx342 Published: 11 July 2017
- Across 16 cohorts enrolling 15662 subjects, higher TMAO levels were associated with greater risk of all-cause mortality (HR: 1.91, 95%CI: 1.40-2.61, P<0.0001), vs ‘low’ TMAO (top vs. bottom tertile).
- When stratified for the presence or absence of CKD, both groups showed a significant association between TMAO and mortality (non-CKD: HR: 1.79, 95%CI: 1.23-2.60, P=0.002, CEK: HR: 2.27, 95%CDI: 1.13-4.58, P=0.02).
- The significant association with mortality also persisted after stratification for geographical location of enrollment (USA, Europe, rest).
- The dose-response meta-analysis showed an RR for all-cause mortality of 7.6% higher risk per each 10 µmol/L increment of TMAO (summary RR: 1.07, 95%CI: 1.04-1.11, P<0.0001). There was evidence for a non-linear association (P non-linearity <0.00001).
- The incidence of MACCE was significantly higher in those with high vs. low TMAO levels (HR: 1.67, 95%CI: 1.33-2.11, P<0.0001).
- Various sensitivity analyses confirmed the observed associations.
- Meta-regression analysis only revealed coronary artery disease as a potential effect modifier, in the sense that studies with a higher percentage of CAD patients showed an increase of the association between high TMAO levels and mortality.
This analysis in a large population shows that high-circulating concentrations of TMAO were associated with higher risk of all-cause mortality and MACCE. A dose-dependent, direct association was observed, and the observed association was consistent across subgroups and all study populations. The shape of the dose-response association requires further characterization.
Surprisingly, observations were consistent for patients with or without CKD, although high circulating TMAO levels have been described in CKD. Nor did geographical localization of populations affect the primary outcome, although dietary patterns may vary, although most studies were conducted in the USA and Europe.