Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO) predicts future major adverse cardiovascular events after myocardial infarction

Aneta Aleksova; Alessandra Lucia Fluca; Mariano Stornaiuolo; Giulia Barbati; Alessandro Pierri; Donna R Zwas; Daniela Santon; Stefano D'Errico; Maria Marketou; Gianfranco Sinagra; Yosefa Avraham; Ettore Novellino; Milijana Janjusevic

doi:10.1016/j.hjc.2024.05.007

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO) predicts future major adverse cardiovascular events after myocardial infarction

Hellenic J Cardiol. 2024 May 8:S1109-9666(24)00111-8. doi: 10.1016/j.hjc.2024.05.007. Online ahead of print.

Affiliations

¹ Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy. Electronic address: aaleksova@units.it.
² Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy.
³ Department of Pharmacy, University of Naples Federico II, Naples, Italy.
⁴ Biostatistics Unit, Department of Medical Sciences, University of Trieste, Italy.
⁵ Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Cardiology, "Antonio Perrino" Hospital, Azienda Sanitaria Locale di Brindisi, Brindisi, Italy.
⁶ Linda Joy Pollin Cardiovascular Wellness Center for Women, Heart Institute, Hadassah University Medical Center, Jerusalem, Israel.
⁷ Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy.
⁸ Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy.
⁹ Heraklion University General Hospital, University of Crete, School of Medicine, Cardiology Department Crete, Greece.
¹⁰ Department of Human Nutrition and Metabolism, School of Public Health Medical Faculty Jerusalem, Jerusalem 91120, Israel.
¹¹ Department of Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy; Inventia Biotech Centro Ricerche Alimentari Healthcare, Caserta, Italy.

PMID: 38729348
DOI: 10.1016/j.hjc.2024.05.007

Abstract

Background and aims: Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome.

Methods and results: Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events) including all-cause mortality, re-infarction or the heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge, (respectively, 7.81 [3.47 - 19.98] vs 3.45 [2.3 - 4.78] μM,p<0.001). After estimating the 3.45 μM TMAO cut-off with the analysis of continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p=0.05). At multivariable Cox analysis, patients from HH/LH group had more than two times higher risk of MACE during the follow-up than LL/HL group (HR=2.15 [95% CI, 1.03 - 4.5], p=0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function.

Conclusions: In patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.

Keywords: MACE; acute myocardial infarction; coronary heart disease; inflammation; trimethylamine N-oxide.