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Simplified plasma essential amino acid-based profiling provides metabolic information and prognostic value additive to traditional risk factors in heart failure

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Abstract

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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Abbreviations

BNP:

B-type natriuretic peptide

CI:

Confidence interval

eGFR:

Estimated glomerular filtration rate

HR:

Hazard ratio

HF:

Heart failure

Leu:

Leucine

LVEF:

Left ventricular ejection fraction

Phe:

Phenylalanine

ROC:

Receiver operating characteristic curve

UPLC:

Ultra-performance liquid chromatography

References

  • Ahmad T, Kelly JP et al (2016) Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support. J Am Coll Cardiol 67(3):291–299

    Article  CAS  Google Scholar 

  • Aquilani R, La Rovere MT et al (2012) Preserved muscle protein metabolism in obese patients with chronic heart failure. Int J Cardiol 160(2):102–108

    Article  Google Scholar 

  • Cheng ML, Wang CH et al (2015) Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol 65(15):1509–1520

    Article  CAS  Google Scholar 

  • Chioncel O, Collins SP et al (2016) Natriuretic peptide-guided management in heart failure. J Cardiovasc Med 17(8):556–568

    Article  CAS  Google Scholar 

  • Frank MP, Powers RW (2007) Simple and rapid quantitative high-performance liquid chromatographic analysis of plasma amino acids. J Chromatogr B Analyt Technol Biomed Life Sci 852(1–2):646–649

    Article  CAS  Google Scholar 

  • Griffin JL, Atherton H et al (2011) Metabolomics as a tool for cardiac research. Nat Rev Cardiol 8(11):630–643

    Article  CAS  Google Scholar 

  • Hakuno D, Hamba Y et al (2015) Plasma amino acid profiling identifies specific amino acid associations with cardiovascular function in patients with systolic heart failure. PLoS One 10(2):e0117325

    Article  Google Scholar 

  • Hunter WG, Kelly JP et al (2016) Metabolic dysfunction in heart failure: diagnostic, prognostic, and pathophysiologic insights from metabolomic profiling. Curr Heart Fail Rep 13(3):119–131

    Article  CAS  Google Scholar 

  • Lavie CJ, Berra K et al (2013) Formal cardiac rehabilitation and exercise training programs in heart failure: evidence for substantial clinical benefits. J Cardiopulm Rehabil Prev 33(4):209–211

    Article  Google Scholar 

  • Liu Z, Barrett EJ (2002) Human protein metabolism: its measurement and regulation. Am J Physiol Endocrinol Metab 283(6):E1105–E1112

    Article  CAS  Google Scholar 

  • Maisel AS, Clopton P et al (2004) Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the breathing not properly (BNP) multinational study. Am Heart J 147(6):1078–1084

    Article  CAS  Google Scholar 

  • Nagabhushan VS, Narasinga Rao BS (1978) Studies on 3-methylhistidine metabolism in children with protein-energy malnutrition. Am J Clin Nutr 31(8):1322–1327

    Article  CAS  Google Scholar 

  • Nishijima Y, Sridhar A et al (2011) Tetrahydrobiopterin depletion and NOS2 uncoupling contribute to heart failure-induced alterations in atrial electrophysiology. Cardiovasc Res 91(1):71–79

    Article  CAS  Google Scholar 

  • Pappa-Louisi A, Nikitas P et al (2007) Optimization of separation and detection of 6-aminoquinolyl derivatives of amino acids by using reversed-phase liquid chromatography with on line UV, fluorescence and electrochemical detection. Anal Chim Acta 593(1):92–97

    Article  CAS  Google Scholar 

  • Rajadurai J, Tse HF et al (2017) Understanding the epidemiology of heart failure to improve management practices: An Asia-Pacific Perspective. J Card Fail 23(4):327–339

    Article  Google Scholar 

  • Rehman SU, Mueller T et al (2008) Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol 52(18):1458–1465

    Article  CAS  Google Scholar 

  • Reid C (2006) Frequency of under- and overfeeding in mechanically ventilated ICU patients: cause and possible consequences. J Hum Nutr Diet 19(1):13–22

    Article  CAS  Google Scholar 

  • Savarese G, Lund LH (2017) Global public health burden of heart failure. Card Fail Rev 3(1):7–11

    Article  Google Scholar 

  • Schooneman MG, Vaz FM et al (2013) Acylcarnitines: reflecting or inflicting insulin resistance? Diabetes 62(1):1–8

    Article  CAS  Google Scholar 

  • Sperry BW, Ruiz G et al (2015) Hospital readmission in heart failure, a novel analysis of a longstanding problem. Heart Fail Rev 20(3):251–258

    Article  Google Scholar 

  • Wang CH, Yang NI et al (2016) Estimating systemic fibrosis by combining galectin-3 and ST2 provides powerful risk stratification value for patients after acute decompensated heart failure. Cardiol J 23(5):563–572

    PubMed  Google Scholar 

  • Wang CH, Cheng ML et al (2017) Metabolic profile provides prognostic value better than galectin-3 in patients with heart failure. J Cardiol 70(1):92–98

    Article  Google Scholar 

  • Ziolo MT, Maier LS et al (2004) Myocyte nitric oxide synthase 2 contributes to blunted beta-adrenergic response in failing human hearts by decreasing Ca2+ transients. Circulation 109(15):1886–1891

    Article  CAS  Google Scholar 

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Acknowledgement

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.

Funding

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).

Author information

Authors and Affiliations

  1. Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taiwan

    Chao-Hung Wang & Min-Hui Liu

  2. Chang Gung University College of Medicine, Taoyuan, Taiwan

    Chao-Hung Wang & Min-Hui Liu

  3. Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan

    Mei-Ling Cheng

  4. Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Mei-Ling Cheng

  5. Clinical Metabolomics Core Laboratory, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Mei-Ling Cheng

  6. Department of Nursing, National Yang-Ming University, Taipei, Taiwan

    Min-Hui Liu

Authors
  1. Chao-Hung Wang
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  2. Mei-Ling Cheng
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  3. Min-Hui Liu
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Correspondence to Chao-Hung Wang.

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The authors declare that they have no conflict of interest.

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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.

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Informed consent was obtained from all individual participants included in the study.

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Handling Editor: D. Tsikas.

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Wang, CH., Cheng, ML. & Liu, MH. Simplified plasma essential amino acid-based profiling provides metabolic information and prognostic value additive to traditional risk factors in heart failure. Amino Acids 50, 1739–1748 (2018). https://doi.org/10.1007/s00726-018-2649-9

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  • DOI: https://doi.org/10.1007/s00726-018-2649-9

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