Tyrosine to threonine ratio was related to heart failure with reduced or mildly reduced ejection fraction

Abstract

Aims: We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF).

Methods and results: The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event-free survival was determined by Kaplan-Meier curves and differences in survival were assessed using log-rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver-operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P < 0.001) while serum threonine (Thr) decreased (165.21 ± 40.09 μmol/L vs. 144.93 ± 44.56 μmol/L vs. 135.25 ± 41.25 μmol/L, P < 0.001). Tyr/Thr ratio was the independent risk factor for the presence of HF in all subjects [odds ratio (OR), 3.510; 95% confidence interval (CI): 2.445-5.040; P < 0.001]. After following up for a mean year (11.10 ± 2.80 months) in 269 HF subjects (75.1% males, mean age 65.2 ± 12.8 years), the higher Tyr/Thr ratio was associated with a higher risk of HF endpoint events in HF subjects [hazard ratio (HR), 2.901; 95% CI: 1.228-6.851; P = 0.015]. By comparing the area under the receiver-operating characteristic curve (AUC), Tyr/Thr ratio was superior to Fischer's ratio (FR) in predicting HF occurrence (0.767:0.573, P < 0.001) or cardiovascular (CV) death (0.715:0.550, P = 0.047).

Conclusions: Circulating elevated Tyr/Thr ratio confer an increased risk for the presence of HF and poor prognosis. Tyr/Thr index outweighs FR index in predicting HF occurrence or CV death.

Keywords: Aetiology; Amino acids; Chronic heart failure; Correlation; HFmrEF; HFrEF; Prognosis; Tyr/Thr ratio.