Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure
- 22 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Heart and Vessels
- Vol. 36 (7), 965-977
- https://doi.org/10.1007/s00380-020-01765-z
Abstract
Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan–Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer’s ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.Keywords
This publication has 53 references indexed in Scilit:
- Preserved muscle protein metabolism in obese patients with chronic heart failureInternational Journal of Cardiology, 2012
- Tetrahydrobiopterin depletion and NOS2 uncoupling contribute to heart failure-induced alterations in atrial electrophysiologyCardiovascular Research, 2011
- Improving Quality of Care and Outcomes for Heart Failure - Role of Registries -Circulation Journal, 2011
- Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit?Cardiovascular Research, 2011
- A Validated Risk Score for In-Hospital Mortality in Patients With Heart Failure From the American Heart Association Get With the Guidelines ProgramCirculation: Cardiovascular Quality and Outcomes, 2010
- Energy metabolism in heart failure and remodellingCardiovascular Research, 2008
- Oral Amino Acid Supplements Improve Exercise Capacities in Elderly Patients with Chronic Heart FailureThe American Journal of Cardiology, 2008
- Impairment in Walking Capacity and Myocardial Function in the Elderly: Is There a Role for Nonpharmacologic Therapy with Nutritional Amino Acid Supplements?The American Journal of Cardiology, 2008
- Amino acids: chemistry and metabolism in normal and hypercatabolic statesThe American Journal of Cardiology, 2004
- ACC/AHA/ASE 2003 Guideline Update for the Clinical Application of Echocardiography: Summary ArticleCirculation, 2003