Association between trimethylamine N‐oxide and prognosis of patients with acute myocardial infarction and heart failure

Abstract

Aims This study aimed to investigate the association between trimethylamine N‐oxide (TMAO) and the prognosis and association between high‐sensitivity C‐reactive protein (hsCRP) and TMAO‐associated cardiovascular risk in patients with acute myocardial infarction (AMI) complicated by heart failure (HF). Methods and results A total of 985 patients presenting with AMI and HF were consecutively enrolled at the Fuwai Hospital between March 2017 and January 2020. Patients were stratified into groups according to tertiles of TMAO levels and the median hsCRP levels. The primary endpoint was major adverse cardiac events (MACE), including all‐cause death, recurrence of myocardial infarction, and rehospitalization due to HF. During a median follow‐up of 716 days, 138 (14.0%) patients experienced MACE. Cox regression analyses showed that the adjusted hazard ratio (HR) for MACE was higher in patients in tertile 3 [TMAO > 9.52 μmol/L, HR: 1.85, 95% confidence interval (CI): 1.18–2.89; P = 0.007] than in tertile 1 (TMAO < 4.74 μmol/L), whereas no significant differences were detected between the patients in tertiles 1 and 2 (TMAO = 4.74–9.52 μmol/L, HR: 0.96, 95% CI: 0.59–1.58; P = 0.874). Restricted cubic spline regression depicted an S‐shaped association between TMAO and MACE (P for nonlinearity = 0.012). In the setting of hsCRP above the median level (6.68 mg/L), per unit increase of TMAO was associated with a 20% increase of MACE risk (HR: 1.20, 95% CI: 1.05–1.37, P = 0.009); increasing tertiles of TMAO were significantly associated with a higher risk of MACE (adjusted P = 0.007 for interaction; P < 0.001 for trend across tertiles). The Kaplan–Meier analysis indicated that patients in tertile 3 had a significantly lower event‐free survival (P = 0.001) when the hsCRP level was above the median level. No similar association between TMAO and MACE was observed when the hsCRP level was below the median level. Conclusions High plasma TMAO levels were independently correlated with poor prognosis in patients with AMI complicated by HF, especially in those with higher hsCRP levels. There was an S‐shaped relationship between TMAO and HR for MACE.

Heart failure and trimethylamine N‐oxide: time to transform a ‘gut feeling’ in a fact?

“…In this context, in the present issue of the ESC Heart Failure journal, Li et al showed that elevated TMAO levels were associated with poor prognosis (i.e. all‐cause death and recurrence of myocardial infarction) in patients with acute myocardial infarction complicated by HF, 29 further validating current understanding 12,36 . Specifically, the authors found that patients with higher sensitivity C‐reactive protein (hsCRP) levels resulted in a further significant stratification of TMAO by tertiles for MACE.…”

“…Amongst the cardiovascular diseases, HF represents a widely investigated disease for association with the gut, with evidence available in both reduced (HFrEF) 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 and preserved (HFpEF) 22 , 23 , 24 , 25 , 26 , 27 phenotypes, as well as in acute 12 , 13 , 28 , 29 , 30 and chronic setting 9 , 10 , 11 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 27 (see Table 1 ). From a pathophysiological point of view, TMAO pathway affects HF in different ways.…”

“…The role of TMAO in risk stratification is not limited to the chronic setting; indeed, TMAO showed its value also in the acute setting, in which elevated levels (except in one investigation) 32 showed to be associated with a poor prognosis. 12 , 13 , 28 , 29 , 30 For instance, in a cohort of 972 acute HF patients, TMAO levels were associated with a more reduced left ventricular ejection fraction, a more advanced clinical status (i.e. NYHA classes III‐IV), and with poor outcome.…”

“…7 Indeed, TMAO is produced through the anaerobic metabolism of choline and L-carnitine, of which eggs and red meat are rich in the Western diet (i.e., based on high fat foods), and diet can be considered as one the of most important factors affecting the gut microbiota composition. 8 Amongst the cardiovascular diseases, HF represents a widely investigated disease for association with the gut, with evidence available in both reduced (HFrEF) [9][10][11][12][13][14][15][16][17][18][19][20][21] and preserved (HFpEF) [22][23][24][25][26][27] phenotypes, as well as in acute 12,13,[28][29][30] and chronic setting [9][10][11][14][15][16][17][18][19][20][21][22][23][24][25]27 (see Table 1). From a pathophysiological point of view, TMAO pathway affects HF in different ways.…”

Relationship between trimethylamine N-oxide and the risk of hypertension in patients with cardiovascular disease: A meta-analysis and dose-response relationship analysis

“…A total of twelve studies on the dose-response relationship between circulating TMAO levels and the risk of hypertension in patients with CVD were included. [16][17][18][20][21][22][23]25,26,[28][29][30] The results of study quality revealed that the NOS scores of 3 studies were 7, [16,25,27] 6 studies had NOS scores of 8, [19,[21][22][23][24]29] and 6 studies had NOS scores of 9. [17,18,20,26,28,30] (the general characteristics of the included studies are illustrated in Table 1).…”