Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation.

Luciani, Marco; Müller, Daniel; Vanetta, Chiara; Diteepeng, Thamonwan; von Eckardstein, Arnold; Aeschbacher, Stefanie; Rodondi, Nicolas; Moschovitis, Giorgio; Reichlin, Tobias; Sinnecker, Tim; Wuerfel, Jens; Bonati, Leo H; Saeedi Saravi, Seyed Soheil; Chocano-Bedoya, Patricia; Coslovsky, Michael; Camici, Giovanni G; Lüscher, Thomas F; Kuehne, Michael; Osswald, Stefan; Conen, David; ... (2023). Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation. Heart (British Cardiac Society), 109(5), pp. 396-404. BMJ Publishing Group 10.1136/heartjnl-2022-321300

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine

UniBE Contributor:

Rodondi, Nicolas, Reichlin, Tobias Roman, Chocano Bedoya, Patricia Orializ

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1468-201X

Publisher:

BMJ Publishing Group

Funders:

[4] Swiss National Science Foundation ; [116] Swiss Heart Foundation = Schweizerische Herzstiftung

Language:

English

Submitter:

Pubmed Import

Date Deposited:

10 Jan 2023 09:49

Last Modified:

19 Feb 2023 06:31

Publisher DOI:

10.1136/heartjnl-2022-321300

PubMed ID:

36593094

Uncontrolled Keywords:

Atrial Fibrillation Biomarkers Magnetic Resonance Angiography Stroke

BORIS DOI:

10.48350/176760

URI:

https://boris.unibe.ch/id/eprint/176760

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