University of Oulu

Fung E, Ng KH, Kwok T, Lui L-T, Palaniswamy S, Chan Q, Lim L-L, Wiklund P, Xie S, Turner C, et al. Divergent Survival Outcomes Associated with Elevated Branched-Chain Amino Acid Levels among Older Adults with or without Hypertension and Diabetes: A Validated, Prospective, Longitudinal Follow-Up Study. Biomolecules. 2023; 13(8):1252.

Divergent survival outcomes associated with elevated branched-chain amino acid levels among older adults with or without hypertension and aiabetes : a validated, prospective, longitudinal follow-up study

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Author: Fung, Erik1,2,3,4,5; Ng, Kwan Hung1,2; Kwok, Timothy1,6;
Organizations: 1Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
2Gerald Choa Cardiac Research Centre and Laboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Hong Kong SAR, China
3Neural, Vascular, Metabolic Biology Programme, and Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
4Division of Cardiology, Department of Medicine, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
5Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK
6CUHK Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
7Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
8Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
9Asia Diabetes Foundation, Shatin, Hong Kong SAR, China
10Faculty of Sport and Health Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland
11The Exercise Translational Medicine Center and Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
12Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK
13Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria 21526, Egypt
14Department of Public Health and Primary Healthcare, School of Public Health, Imperial College London, London W2 1PG, UK
15Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
16Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, China
17Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
18Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UK
19Unit of Primary Health Care, Oulu University Hospital, 90014 Oulu, Finland
20CUHK Jockey Club Institute of Ageing, The Chinese University of Hong Kong, Hong Kong SAR, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.2 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2023
Publish Date: 2023-10-24


Branched-chain amino acids are critical metabolic intermediates that can indicate increased risk of cardiometabolic disease when levels are elevated or, alternatively, suggest sufficient mitochondrial energy metabolism and reserve in old age. The interpretation of BCAA levels can be context-dependent, and it remains unclear whether abnormal levels can inform prognosis. This prospective longitudinal study aimed to determine the interrelationship between mortality hazard and fasting serum BCAA levels among older men and women aged ≥65 years with or without hypertension and diabetes mellitus. At baseline (0Y), fasting serum BCAA concentration in 2997 community-living older men and women were measured. Approximately 14 years later (14Y), 860 study participants returned for repeat measurements. Deaths were analysed and classified into cardiovascular and non-cardiovascular causes using International Classification of Diseases codes. Survival analysis and multivariable Cox regression were performed. During a median follow-up of 17Y, 971 (78.6%) non-cardiovascular and 263 (21.4%) cardiovascular deaths occurred among 1235 (41.2%) deceased (median age, 85.8 years [IQR 81.7–89.7]). From 0Y to 14Y, BCAA levels declined in both sexes, whereas serum creatinine concentration increased (both p < 0.0001). In older adults without hypertension or diabetes mellitus, the relationship between mortality hazard and BCAA level was linear and above-median BCAA levels were associated with improved survival, whereas in the presence of cardiometabolic disease the relationship was U-shaped. Overall, adjusted Cox regression determined that each 10% increment in BCAA concentration was associated with a 7% (p = 0.0002) and 16% (p = 0.0057) reduction in mortality hazard estimated at 0Y and 14Y, respectively. Our findings suggested that abnormally high or low (dyshomeostatic) BCAA levels among older adults with hypertension and/or diabetes mellitus were associated with increased mortality, whereas in those with neither disease, increased BCAA levels was associated with improved survival, particularly in the oldest-old.

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Series: Biomolecules
ISSN: 2218-273X
ISSN-E: 2218-273X
ISSN-L: 2218-273X
Volume: 13
Issue: 8
Article number: 1252
DOI: 10.3390/biom13081252
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The authors thank the Research Grants Council of the University Grants Committee of Hong Kong, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, United States of America for funding support from 2003 to 2008 (project number 1R01AR049439-01A1). E.F. is the recipient of research grants from the Research Grants Council of Hong Kong, the Health and Medical Research Fund, the Food and Health Bureau of the Hong Kong SAR Government, and the United States National Academy of Medicine. M.R.J. is supported by the European Union’s Horizon 2020 programme EDCMET (grant number 825762); Academy of Finland, grant numbers 24300796, 24302031, 285547 (EGEA); the Medical Research Council (MRC) UK (grant number G0601653); Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE (Nutrition & Epigenome, The Joint Programming Initiative a Healthy Diet for a Healthy Life (JPI HDHL/EU-H2020)); The NFBC1966 31-y follow-up study received financial support from University of Oulu Grant no. 65354, Oulu University Hospital Grant nos. 2/97, 8/97, Ministry of Health and Social Affairs Grant nos. 23/251/97, 160/97, 190/97, National Institute for Health and Welfare, Helsinki Grant no. 54121, Regional Institute of Occupational Health, Oulu, Finland Grant nos. 50621, 54231, and Jenny and Antti Wihuri Foundation. The funding sources had no influence on the study design, collection, analysis, interpretation of data, writing of the report, or on the decision to submit the article.
EU Grant Number: (825762) EDCMET - Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (