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Review
. 2020 Jan 9;20(1):7.
doi: 10.1186/s12872-019-01310-5.

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

Miao-En Yao  1   2   3 , Peng-Da Liao  4 , Xu-Jie Zhao  4 , Lei Wang  5
Affiliations
Review

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

Miao-En Yao et al. BMC Cardiovasc Disord. .

Abstract

Background: Previous clinical studies have suggested that trimethylamine-N-oxide (TMAO) could contribute to the development of atherosclerosis cardiovascular disease. However, the synthetic analysis in coronary heart disease (CHD) was not yet performed. We aimed to clarify the relationship between elevated plasma concentrations of TMAO and the incidence of major adverse cardiovascular events (MACE) in CHD patients.

Methods: Meta-analysis and dose-response analysis of hazard ratio data from prospective observational studies reporting on the association between TMAO plasma concentrations and the incidence of MACE in patients with CHD were conducted.

Results: Of the 2369 published articles identified in the search, seven papers, with data from nine cohort studies (10,301 patients), were included in the meta-analysis. Combined data showed that elevated plasma TMAO concentrations could increase 58% higher risk of MACE in patients with CHD (hazard ratios [HR]: 1.58; 95% confidence interval [CI] = 1.35-1.84, P = 0.000). For follow-up ≥ 1 year, it was associated with 62% higher risk of MACE in patients with longer-term than shorter-term (HR for follow-up ≥ 4 years: 1.96; 95% CI = 1.52-2.52 vs one to 3 years: 1.34; 95% CI = 1.26-1.43, P = 0.004). The dose-response analysis revealed a 'J' shaped association between TMAO concentration and the incidence of MACE (P = 0.033), with the concentration above 5.1 μmol/L being associated with HR of > 1.

Conclusions: Elevated levels of TMAO are associated with an increased incidence of MACE in patients with CHD. TMAO concentration of 5.1 μmol/L may be a cut-off value for prognosis.

Keywords: Coronary disease; Differential threshold; Dose-response relationship; Meta-analysis as topic; Trimethyloxamine.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of study selection. CNKI, China National Knowledge Infrastructure; CHD, coronary heart disease; VIP, Chinese VIP Information
Fig. 2
Fig. 2
The relationship between TMAO plasma levels and incidence of MACE. In ACS and chronic CHD patients (a); in CHD patients with in-hospital observation and a follow-up of 1–3 years and ≥ 4 years (b). ACS, acute coronary syndrome; CC, Cleveland acute coronary syndrome cohort; CHD, coronary heart diseases; CI, confidence interval; HR, hazard ratio; MACE, major adverse cardiovascular event; SC, Swiss ACS cohort; TMAO, trimethylamine-N-oxide
Fig. 3
Fig. 3
Concentration-risk analysis between plasma concentrations of TMAO and HR for MACE in patients with CHD. Used a restricted cubic splines in a non-linear random-effects model The solid line and the long dashed line represents the estimated HR and its 95% CI of the nonlinear relationship, while the short dashed line represents the linear relationship. Before the red line, the curve of HR tends to be flat, whereas after the blue line, the curve tends to be steep, and TMAO presents as a risk factor for MACE. CHD, coronary heart diseases; CI, confidence interval; HR, hazard ratio; MACE, major adverse cardiovascular event; TMAO, trimethylamine-N-oxide
See this image and copyright information in PMC

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