Trimethylamine-N-oxide tied to cardiovascular mortality, vascular brain lesions in afib

 

Marco Luciani1,2, 

Daniel Müller3,4, 

Chiara Vanetta5, 

Thamonwan Diteepeng2, 

Arnold von Eckardstein3, 

http://orcid.org/0000-0001-8134-2421Stefanie Aeschbacher6,7, 

Nicolas Rodondi8,9, 

http://orcid.org/0000-0002-4043-8061Giorgio Moschovitis10, 

Tobias Reichlin11, 

Tim Sinnecker12,13, 

Jens Wuerfel13,14, 

Leo H Bonati12,15, 

Seyed Soheil Saeedi Saravi1,2, 

Patricia Chocano-Bedoya8,16, 

Michael Coslovsky7,17, 

Giovanni G Camici2, 

Thomas F Lüscher2,18,19, 

Michael Kuehne6,20, 

Stefan Osswald6,20, 

David Conen21, 

http://orcid.org/0000-0002-7199-0406Jürg Hans Beer1,2

DOI: http://dx.doi.org/10.1136/heartjnl-2022-321300

Abstract

Objective Trimethylamine-N-oxide (TMAO) is a metabolite derived from the microbial processing of dietary phosphatidylcholine and carnitine and the subsequent hepatic oxidation. Due to its prothrombotic and inflammatory mechanisms, we aimed to assess its role in the prediction of adverse events in a susceptible population, namely patients with atrial fibrillation.

Methods Baseline TMAO plasma levels were measured by liquid chromatography-tandem mass spectrometry in 2379 subjects from the ongoing Swiss Atrial Fibrillation cohort. 1722 underwent brain MRI at baseline. Participants were prospectively followed for 4 years (Q1–Q3: 3.0–5.0) and stratified into baseline TMAO tertiles. Cox proportional hazards and linear and logistic mixed effect models were employed adjusting for risk factors.

Results Subjects in the highest TMAO tertile were older (75.4±8.1 vs 70.6±8.5 years, p<0.01), had poorer renal function (median glomerular filtration rate: 49.0 mL/min/1.73 m2 (35.6–62.5) vs 67.3 mL/min/1.73 m2 (57.8–78.9), p<0.01), were more likely to have diabetes (26.9% vs 9.1%, p<0.01) and had a higher prevalence of heart failure (37.9% vs 15.8%, p<0.01) compared with patients in the lowest tertile. Oral anticoagulants were taken by 89.1%, 94.0% and 88.2% of participants, respectively (from high to low tertiles). Cox models, adjusting for baseline covariates, showed increased total mortality (HR 1.65, 95% CI 1.17 to 2.32, p<0.01) as well as cardiovascular mortality (HR 1.86, 95% CI 1.21 to 2.88, p<0.01) in the highest compared with the lowest tertile. When present, subjects in the highest tertile had more voluminous, large, non-cortical and cortical infarcts on MRI (log-transformed volumes; exponentiated estimate 1.89, 95% CI 1.11 to 3.21, p=0.02) and a higher chance of small non-cortical infarcts (OR 1.61, 95% CI 1.16 to 2.22, p<0.01).

Conclusions High levels of TMAO are associated with increased risk of cardiovascular mortality and cerebral infarction in patients with atrial fibrillation.

Trial registration number NCT02105844.

https://heart.bmj.com/content/early/2023/01/01/heartjnl-2022-321300