Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI

Abstract

Trimethylamine N-oxide (TMAO), a metabolite derived from the gut microbiota, is proatherogenic and associated with cardiovascular events. However, the change in TMAO with secondary prevention therapies for ST-segment elevation acute myocardial infarction (STEMI) remains unclear. The purpose of this study was to investigate the sequential change in TMAO levels in response to the current secondary prevention therapies in patients with STEMI and the clinical impact of TMAO levels on cardiovascular events We included 112 STEMI patients and measured plasma TMAO levels at the onset of STEMI and 10 months later (chronic phase). After the chronic-phase assessment, patients were followed up for cardiovascular events. Plasma TMAO levels significantly increased from the acute phase to the chronic phase of STEMI (median: 5.63 to 6.76 μM, P = 0.048). During a median period of 5.4 years, 17 patients experienced events. The chronic-phase TMAO level independently predicted future cardiovascular events (adjusted hazard ratio for 0.1 increase in log chronic-phase TMAO level: 1.343, 95% confidence interval 1.122–1.636, P = 0.001), but the acute-phase TMAO level did not. This study demonstrated the clinical importance of the chronic-phase TMAO levels on future cardiovascular events in patients after STEMI.

Trimethylamine-N-oxide has prognostic value in coronary heart disease: a meta-analysis and dose-response analysis

“…Summary HR and 95% CI were calculated for the risk of MACE associated with high concentrations of TMAO in comparison with low concentrations [6,7,[9][10][11], or increments of one SD [5,8], using a random-effects model. The high TMAO concentration group refers to the highest quartile [7,9,10], tertile [6] or the higher one [11], while the low concentration group refers to the lowest or lower one. We pooled the natural logarithm of HRs and weighted HRs according to the method of inverse variance, considering a P < 0.05 from a two tailed analysis to be statistically significant.…”

“…We pooled the natural logarithm of HRs and weighted HRs according to the method of inverse variance, considering a P < 0.05 from a two tailed analysis to be statistically significant. Subgroup analyses for patients with ACS [6,[8][9][10][11] and chronic CHD [5,7] were conducted. Taking follow-up time into account, subgroups analyses were also performed for a follow-up duration of in-hospital [10], one to 3 years [5,8,9] and ≥ 4 years [6,7,9,11].…”

“…In total, seven publications, reporting on nine cohort studies, were selected for inclusion in the analysis [5][6][7][8][9][10][11]. A previous meta-analysis by Heianza Y. and colleagues was identified in the search results, but no additional and relevant publications were found in the reference list [26].…”

“…As the accurate biomarkers of prognosis being of increasing clinical value, more studies [3,4] evaluating their validity of prognostic value have been performed. Currently, a metabolite called trimethylamine-N-oxide (TMAO) has recently shown association with the incidence of major adverse cardiac events (MACE) in patients with CHD [5][6][7][8][9][10][11]. In food such as red meat and eggs, choline and carnitine are the most natural source of TMAO.…”

“…Clinical epidemiology demonstrates a positive correlation between higher plasma TMAO concentrations and an increased incidence of MACE [5][6][7][8][9][10]. Recently, one study [11] shows no significant correlation between acute-phase TMAO level and the incidence of MACE. A previous meta-analysis reveals a positive dose-dependent association between TMAO concentration and higher risk of MACE [17].…”