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

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.