High levels of Trimethylamine-N-oxide increase risk of cerebral infarction and mortality in AF patients

In individuals with atrial fibrillation, high levels of trimethylamine-N-oxide (TMAO) are related with an increased risk of cardiovascular death and cerebral infarction, says an article published in BMJ Heart.

Trimethylamine-N-oxide is a metabolite produced by the microbial breakdown of dietary phosphatidylcholine and carnitine, followed by hepatic oxidation. Marco Luciani and colleagues undertook this study to investigate its function in the prediction of adverse outcomes in a vulnerable group, specifically patients with atrial fibrillation, due to its prothrombotic and inflammatory processes.

Liquid chromatography-tandem mass spectrometry was used to quantify baseline TMAO plasma levels in 2379 participants from the ongoing Swiss Atrial Fibrillation cohort. At the outset, 1722 people had brain MRIs. Participants were tracked prospectively for four years (Q1-Q3: 3.0-5.0) and classified into TMAO tertiles at the start. To account for risk variables, linear and logistic mixed effect models and Cox proportional hazards were used.

The key findings of this study were:

1. In comparison to patients in the lowest tertile, subjects in the highest TMAO tertile were older, had worse renal function, were more likely to have diabetes, and had a greater prevalence of heart failure. 89.1%, 94.0%, and 88.2% of individuals, respectively, used oral anticoagulants (from high to low tertiles).

2. When baseline variables were taken into account, Cox models revealed higher overall mortality and cardiovascular mortality in the highest tertile compared to the lowest tertile.

3. On MRI, participants in the highest tertile were more likely to have tiny non-cortical infarcts and more likely to have copious, massive, non-cortical and cortical infarcts (log-transformed volumes; exponentiated estimate 1.89, 95% CI 1.11 to 3.21, p=0.02).

Reference:

Luciani, M., Müller, D., Vanetta, C., Diteepeng, T., von Eckardstein, A., Aeschbacher, S., Rodondi, N., Moschovitis, G., Reichlin, T., Sinnecker, T., Wuerfel, J., Coslovsky, M., Camici, G. G., Lüscher, T. F., Kuehne, M., Osswald, S., … Beer, J. H. (2023). Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation. In Heart. BMJ. https://doi.org/10.1136/heartjnl-2022-321300