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. 2022 Sep 21:9:1000815.
doi: 10.3389/fcvm.2022.1000815. eCollection 2022.

Plasma trimethylamine-N-oxide, its precursors and risk of cardiovascular events in patients with acute coronary syndrome: Mediating effects of renal function

Raul Sanchez-Gimenez  1   2   3 , Óscar M Peiró  1   2   3 , Gil Bonet  1   2   3 , Anna Carrasquer  1   2   3 , Georgios A Fragkiadakis  4 , Mònica Bulló  2   5   6 , Christopher Papandreou  2 , Alfredo Bardaji  1   2   3
Affiliations

Plasma trimethylamine-N-oxide, its precursors and risk of cardiovascular events in patients with acute coronary syndrome: Mediating effects of renal function

Raul Sanchez-Gimenez et al. Front Cardiovasc Med. .

Abstract

Aims: To examine associations of the gut microbial metabolite trimethylamine-N-oxide (TMAO) and its precursors with risk of cardiovascular events in acute coronary syndrome (ACS), and determine whether these associations were mediated by renal function.

Methods: In this prospective cohort study, we included 309 patients with ACS. During a mean follow-up of 6.7 years, 131 patients developed major adverse cardiovascular events (MACE) (myocardial infarction, hospitalization for heart failure, and all-cause mortality). Plasma concentrations of TMAO, trimethylamine (TMA), choline, betaine, dimethylglycine and L-carnitine were profiled by liquid chromatography tandem mass spectrometry. Hazard ratios were estimated with multivariable Cox regression models. The mediating role of estimated glomerular filtration rate (eGFR) was tested under a counterfactual framework.

Results: After adjustment for traditional cardiovascular risk factors and medications, participants in the highest tertile vs. the lowest tertile of baseline TMAO and dimethylglycine concentrations had a higher risk of MACE [(HR: 1.83; 95% CI: 1.08, 3.09) and (HR: 2.26; 95% CI: 1.17, 3.99), respectively]. However, with regards to TMAO these associations were no longer significant, whereas for dimethylglycine, the associations were attenuated after additional adjustment for eGFR. eGFR mediated the associations of TMAO (58%) and dimethylglycine (32%) with MACE incidence. The associations between dimethylglycine and incident MACE were confirmed in an internal validation. No significant associations were found for TMA, choline, betaine and L-carnitine.

Conclusion: These findings suggest that renal function may be a key mediator in the association of plasma TMAO with the development of cardiovascular events after ACS. The present findings also support a role of dimethylglycine in the pathogenesis of MACE, which may be mediated, at least partially, by renal function.

Keywords: acute coronary syndrome; major adverse cardiovascular events; metabolites; prognostic; trimethylamine-N-oxide.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Mueller C. Biomarkers and acute coronary syndromes: an update. Eur Heart J. (2014) 35:552–6. 10.1093/eurheartj/eht530 - DOI - PubMed
    1. Hammer Y, Iakobishvili Z, Hasdai D, Goldenberg I, Shlomo N, Einhorn M, et al. . Guideline-recommended therapies and clinical outcomes according to the risk for recurrent cardiovascular events after an acute coronary syndrome. J Am Heart Assoc. (2018) 7:e009885. 10.1161/JAHA.118.009885 - DOI - PMC - PubMed
    1. O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Jr, Chung MK, de Lemos JA, et al. . 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. (2013) 127:e362–425. 10.1161/CIR.0b013e3182742cf6 - DOI - PubMed
    1. Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Jr, Ganiats TG, Holmes DR, Jr, et al. . 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. (2014) 130:e344–426. 10.1161/CIR.0000000000000134 - DOI - PubMed
    1. Salvagno GL, Pavan C. Prognostic biomarkers in acute coronary syndrome. Ann Transl Med. (2016) 4:258. 10.21037/atm.2016.06.36 - DOI - PMC - PubMed