Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation. Issue 5 (2nd January 2023)

• Record Type: Journal Article
• Authors: 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; Beer, Jürg Hans
• Other Names: author non-byline.; Aeschbacher Stefanie author non-byline.; Auberson Chloé author non-byline.; Blum Steffen author non-byline.; Bonati Leo author non-byline.; Ceylan Selinda author non-byline.; Conen David author non-byline.; Doerpfeld Simone Evers- author non-byline.; Eken Ceylan author non-byline.; Girod Marc author non-byline.; Hennings Elisa author non-byline.; Herber Elena author non-byline.; Iten Vasco author non-byline.; Krisai Philipp author non-byline.; Kühne Michael author non-byline.; Lischer Mirko author non-byline.; Meyer-Zürn Christine author non-byline.; Meyre Pascal author non-byline.; Monsch Andreas U. author non-byline.; Müller Christian author non-byline.; Osswald Stefan author non-byline.; Paladini Rebecca author non-byline.; Springer Anne author non-byline.; Sticherling Christian author non-byline.; Szucs Thomas author non-byline.; Völlmin Gian author non-byline.; Osswald Stefan author non-byline.; Kühne Michael author non-byline.; Aujesky Drahomir author non-byline.; Fischer Urs author non-byline.; Fuhrer Juerg author non-byline.; Roten Laurent author non-byline.; Jung Simon author non-byline.; Mattle Heinrich author non-byline.; Adam Luise author non-byline.; Aubert Carole Elodie author non-byline.; Feller Martin author non-byline.; Loewe Axel author non-byline.; Moutzouri Elisavet author non-byline.; Schneider Claudio author non-byline.; Flückiger Tanja author non-byline.; Groen Cindy author non-byline.; Ehrsam Lukas author non-byline.; Hellrigl Sven author non-byline.; Nuoffer Alexandra author non-byline.; Rakovic Damiana author non-byline.; Schwab Nathalie author non-byline.; Wenger Rylana author non-byline.; Zarrabi Saffari Tu Hanh author non-byline.; Rodondi Nicolas author non-byline.; Reichlin Tobias author non-byline.; Beynon Christopher author non-byline.; Dillier Roger author non-byline.; Deubelbeiss Michèle author non-byline.; Eberli Franz author non-byline.; Franzini Christine author non-byline.; Juchli Isabel author non-byline.; Liedtke Claudia author non-byline.; Murugiah Samira author non-byline.; Nadler Jacqueline author non-byline.; Obst Thayze author non-byline.; Roth Jasmin author non-byline.; Schlomowitsch Fiona author non-byline.; Schneider Xiaoye author non-byline.; Studerus Katrin author non-byline.; Tynan Noreen author non-byline.; Weishaupt Dominik author non-byline.; Müller Andreas author non-byline.; Fontana Simone author non-byline.; Friedli Corinne author non-byline.; Kuest Silke author non-byline.; Scheuch Karin author non-byline.; Hischier Denise author non-byline.; Bonetti Nicole author non-byline.; Grau Alexandra author non-byline.; Villinger Jonas author non-byline.; Laube Eva author non-byline.; Baumgartner Philipp author non-byline.; Filipovic Mark author non-byline.; Frick Marcel author non-byline.; Montrasio Giulia author non-byline.; Leuenberger Stefanie author non-byline.; Rutz Franziska author non-byline.; Beer Jürg-Hans author non-byline.; Auricchio Angelo author non-byline.; Anesini Adriana author non-byline.; Camporini Cristina author non-byline.; Conte Giulio author non-byline.; Caputo Maria Luce author non-byline.; Regoli Francois author non-byline.; Moccetti Tiziano author non-byline.; Brenner Roman author non-byline.; Altmann David author non-byline.; Gemperle Michaela author non-byline.; Ammann Peter author non-byline.; Firmann Mathieu author non-byline.; Foucras Sandrine author non-byline.; Rime Martine author non-byline.; Hayoz Daniel author non-byline.; Berte Benjamin author non-byline.; Justi Virgina author non-byline.; Kellner-Weldon Frauke author non-byline.; Mehmann Brigitta author non-byline.; Meier Sonja author non-byline.; Roth Myriam author non-byline.; Ruckli-Kaeppeli Andrea author non-byline.; Russi Ian author non-byline.; Schmidt Kai author non-byline.; Young Mabelle author non-byline.; Zbinden Melanie author non-byline.; Kobza Richard author non-byline.; Cereda Carlo author non-byline.; Cianfoni Alessandro author non-byline.; Perna Maria Luisa De author non-byline.; Frangi-Kultalahti Jane author non-byline.; Mayer Melchiorre Patrizia Assunta author non-byline.; Pin Anica author non-byline.; Terrot Tatiana author non-byline.; Vicari Luisa author non-byline.; Moschovitis Giorgio author non-byline.; Ehret Georg author non-byline.; Gallet Hervé author non-byline.; Guillermet Elise author non-byline.; Lazeyras Francois author non-byline.; Lovblad Karl-Olof author non-byline.; Perret Patrick author non-byline.; Tavel Philippe author non-byline.; Teres Cheryl author non-byline.; Shah Dipen author non-byline.; Lauriers Nathalie author non-byline.; Méan Marie author non-byline.; Salzmann Sandrine author non-byline.; Schläpfer Jürg author non-byline.; Porretta Alessandra Pia author non-byline.; Grêt Andrea author non-byline.; Novak Jan author non-byline.; Vitelli Sandra author non-byline.; Stephan Frank-Peter author non-byline.; Frangi-Kultalahti Jane author non-byline.; Gallino Augusto author non-byline.; Vicari Luisa author non-byline.; Valentino Marcello Di author non-byline.; Aebersold Helena author non-byline.; Foster Fabienne author non-byline.; Schwenkglenks Matthias author non-byline.; Würfel Jens author non-byline.; Altermatt Anna author non-byline.; Amann Michael author non-byline.; Düring Marco author non-byline.; Huber Petra author non-byline.; Ruberte Esther author non-byline.; Sinnecker Tim author non-byline.; Zuber Vanessa author non-byline.; Coslovsky Michael author non-byline.; Benkert Pascal author non-byline.; Dutilh Gilles author non-byline.; Markovic Milica author non-byline.; Neuschwander Pia author non-byline.; Simon Patrick author non-byline.; Schmid Ramun author non-byline.;
• Is Part Of: Heart. Volume 109:Issue 5(2023)
• Page Start: 396
• Page End: 404
• Publication Date: 2023-01-02
• Subjects: Atrial Fibrillation -- Magnetic Resonance Angiography -- Biomarkers -- Stroke; Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2022-321300
• Languages: English
• ISSNs: 1355-6037

Abstract

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 m 2 (35.6–62.5) vs 67.3 mL/min/1.73 m 2 (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 .