Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors.

Li, Xinmin S; Obeid, Slayman; Klingenberg, Roland; Gencer, Baris; Mach, François; Räber, Lorenz; Windecker, Stephan; Rodondi, Nicolas; Nanchen, David; Muller, Olivier; Miranda, Melroy X; Matter, Christian M; Wu, Yuping; Li, Lin; Wang, Zeneng; Alamri, Hassan S; Gogonea, Valentin; Chung, Yoon-Mi; Tang, W H Wilson; Hazen, Stanley L; ... (2017). Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors. European Heart Journal, 38(11), pp. 814-824. Oxford University Press 10.1093/eurheartj/ehw582

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AIMS Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown. METHODS AND RESULTS We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts. In the Cleveland Cohort, comprised of sequential subjects (n = 530) presenting to the Emergency Department (ED) with chest pain of suspected cardiac origin, an elevated plasma TMAO level at presentation was independently associated with risk of major adverse cardiac events (MACE, including myocardial infarction, stroke, need for revascularization, or death) over the ensuing 30-day (4th quartile (Q4) adjusted odds ratio (OR) 6.30, 95% confidence interval (CI), 1.89-21.0, P < 0.01) and 6-month (Q4 adjusted OR 5.65, 95%CI, 1.91-16.7; P < 0.01) intervals. TMAO levels were also a significant predictor of the long term (7-year) mortality (Q4 adjusted HR 1.81, 95%CI, 1.04-3.15; P < 0.05). Interestingly, TMAO level at initial presentation predicted risk of incident MACE over the near-term (30 days and 6 months) even among subjects who were initially negative for troponin T (< 0.1 ng/mL) (30 days, Q4 adjusted OR 5.83, 95%CI, 1.79-19.03; P < 0.01). The prognostic value of TMAO was also assessed in an independent multicentre Swiss Cohort of ACS patients (n = 1683) who underwent coronary angiography. Trimethylamine N-oxide again predicted enhanced MACE risk (1-year) (adjusted Q4 hazard ratios: 1.57, 95% CI, 1.03-2.41; P <0.05). CONCLUSION Plasma TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events, and may thus provide clinical utility in risk stratification among subjects presenting with suspected ACS.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Kardiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Kardiologie

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Räber, Lorenz; Windecker, Stephan and Rodondi, Nicolas

Subjects:

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

ISSN:

0195-668X

Publisher:

Oxford University Press

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

16 Feb 2017 10:42

Last Modified:

25 Apr 2017 13:56

Publisher DOI:

10.1093/eurheartj/ehw582

PubMed ID:

28077467

Uncontrolled Keywords:

Acute coronary syndrome; All-cause mortality; Choline; Gut microbiota; Incident major adverse cardiac events; Risk stratification; Trimethylamine N-oxide

BORIS DOI:

10.7892/boris.95968

URI:

https://boris.unibe.ch/id/eprint/95968

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