In heart failure (HF), metabolic disturbances represent functional perturbations in peripheral tissues and also predict patient outcomes. This study developed a simplified essential amino acid-based profile and tested whether it could improve prognostication. Plasma essential amino acids and lipidomics were measured on 1084 participants. The initial cohort included 94 normal controls and 599 patients hospitalized due to acute/decompensated HF. The validation cohort included 391 HF patients. Patients were followed for composite events (death/HF related re-hospitalization) and were categorized into three groups: high risk type 1 (leucine ≥145 μM and phenylalanine ≥ 88.9 μM), high risk type 2 (leucine < 81.2 μM), and low risk (other). Types 1 and 2 were associated with higher event rates [hazard ratio (95% confidence intervals) = 1.88 (1.27–2.79) and 7.71 (4.97–11.9), respectively, p < 0.001]. Compared to the low-risk group, both types of high-risk patients were older and had lower blood pressure and estimated glomerular filtration rates, but higher B-type natriuretic peptides (BNP). In addition, type 1 was associated with more incompletely metabolized lipids in the blood; type 2 patients had lower body mass indexes, rates of using guideline-based medications, and levels of cholesterol, hemoglobin, and albumin. The prognostic value of types 1 and 2 remained significant after adjusting for age, BNP and other risk factors. The value of using high-risk types for prognosis was confirmed in the validation cohort. In conclusion, simplified essential amino acid-based profiling identified two high-risk populations and provided metabolic information and prognostic value additive to traditional risk factors.
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The authors thank Cardiology Section, Department of Internal Medicine, Chang Gung Memorial Hospital, Keeling, Taiwan for providing samples from patients and normal controls. We also thank Healthy Aging Research Center, Chang Gung University from the Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan.
This study was supported in part by the Ministry of Science and Technology of Taiwan (MOST105-2314-B-182-046-MY2, 107-2314-B-182-071-MY2); Chang Gung Memorial Hospital (CMRPG2C0313, G2E0351, G2G0601, G2G0581); and the Ministry of Education of Taiwan (EMRPD1G0251, EMRPD1H0401).
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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