The relationship between trimethylamine-N-oxide and the risk of acute ischemic stroke: A dose‒response meta-analysis.
Level 4 - case-series / case-control
Systematic review and meta-analysis of predominantly case-control studies (17 case-control, 3 cohort)
PubMed 37883346 · doi:10.1371/journal.pone.0293275
What was done
A systematic review and dose-response meta-analysis was conducted across seven databases (PubMed, Embase, Cochrane, CNKI, VIP, Wanfang, CBM) through September 23, 2023. Investigators included 20 observational studies (17 case-control and 3 cohort studies) comprising 9,141 total participants (5,283 acute ischemic stroke cases and 3,858 controls). Standardized mean differences (SMD) for serum/plasma trimethylamine-N-oxide (TMAO) concentrations were pooled using a random-effects model, and a dose-response meta-analysis was conducted using data from three eligible case-control studies.
What was found
Acute ischemic stroke patients had significantly higher circulating TMAO levels compared to controls (SMD = 1.27; 95% CI: 0.90 to 1.61, P < 0.001). The dose-response meta-analysis showed a 12.1% relative increase in the risk of acute ischemic stroke for each 1 μmol/L increase in TMAO concentration (RR = 1.12; 95% CI: 1.07 to 1.17; P < 0.05; I² = 1.6%, P = 0.4484).
Why it matters
This review quantitatively synthesizes observational data linking elevated circulating TMAO to an increased risk of acute ischemic stroke, demonstrating a significant dose-response relationship.
Limits
The primary evidence base consists of retrospective case-control designs (17 of 20 studies), which cannot establish temporal causality and leaves open the possibility of reverse causation. The dose-response analysis included only three case-control studies. The abstract does not specify whether pooled analyses adjusted for essential confounders such as renal function, diet, or established cardiovascular risk factors.