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.