University of Oulu

Delles, C., Rankin, N., Boachie, C., McConnachie, A., Ford, I., Kangas, A., Soininen, P., Trompet, S., Mooijaart, S., Jukema, J., Zannad, F., Ala-Korpela, M., Salomaa, V., Havulinna, A., Welsh, P., Würtz, P., Sattar, N. (2017) Nuclear magnetic resonance-based metabolomics identifies phenylalanine as a novel predictor of incident heart failure hospitalisation: results from PROSPER and FINRISK 1997. European Journal of Heart Failure, 20 (4), 663-673. doi:10.1002/ejhf.1076

Nuclear magnetic resonance‐based metabolomics identifies phenylalanine as a novel predictor of incident heart failure hospitalisation : results from PROSPER and FINRISK 1997

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Author: Delles, Christian1; Rankin, Naomi J.1,2; Boachie, Charles3;
Organizations: 1Institute of Cardiovascular and Medical Sciences (ICAMS), BHF Glasgow Cardiovascular Research Centre, University of Glasgow
2Glasgow Polyomics, Joseph Black Building, University of Glasgow
3Robertson Centre for Biostatistics, Boyd Orr Building, University of Glasgow
4Computational Medicine, Faculty of Medicine and Biocenter Oulu, University of Oulu
5NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland
6Leiden University Medical Centre
7Inserm Centre d'Investigation Clinique (CIC) 1443, Université de Lorraine
8Centre Hospitalier Régional Universitaire (CHRU) de Nancy
9Medical Research Council Integrative Epidemiology Unit, University of Bristol
10Population Health Science, Bristol Medical School, University of Bristol
11Systems Epidemiology, Baker Heart and Diabetes Institute
12Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University
13National Institute for Health and Welfare (THL)
14Institute for Molecular Medicine (FIMM), University of Helsinki
15Research Programs Unit, Diabetes and Obesity, University of Helsinki
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2018082333986
Language: English
Published: John Wiley & Sons, 2018
Publish Date: 2018-08-23
Description:

Abstract

Aims: We investigated the association between quantified metabolite, lipid and lipoprotein measures and incident heart failure hospitalisation (HFH) in the elderly, and examined whether circulating metabolic measures improve HFH prediction.

Methods and results: Overall, 80 metabolic measures from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial were measured by proton nuclear magnetic resonance spectroscopy (n  = 5341; 182 HFH events during 2.7‐year follow‐up). We repeated the work in FINRISK 1997 (n = 7330; 133 HFH events during 5‐year follow‐up). In PROSPER, the circulating concentrations of 13 metabolic measures were found to be significantly different in those who were later hospitalised for heart failure after correction for multiple comparisons. These included creatinine, phenylalanine, glycoprotein acetyls, 3‐hydroxybutyrate, and various high‐density lipoprotein measures. In Cox models, two metabolites were associated with risk of HFH after adjustment for clinical risk factors and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP): phenylalanine [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.10–1.53; P  = 0.002] and acetate (HR 0.81, 95% CI 0.68–0.98; P  = 0.026). Both were retained in the final model after backward elimination. Compared to a model with established risk factors and NT‐proBNP, this model did not improve the C‐index but did improve the overall continuous net reclassification index (NRI 0.21; 95% CI 0.06–0.35; P = 0.007) due to improvement in classification of non‐cases (NRI 0.14; 95% CI 0.12–0.17; P < 0.001). Phenylalanine was replicated as a predictor of HFH in FINRISK 1997 (HR 1.23, 95% CI 1.03–1.48; P = 0.023).

Conclusion: Our findings identify phenylalanine as a novel predictor of incident HFH, although prediction gains are low. Further mechanistic studies appear warranted.

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Volume: 20
Issue: 4
Pages: 663 - 673
DOI: 10.1002/ejhf.1076
OADOI: https://oadoi.org/10.1002/ejhf.1076
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 Internal medicine
Subjects:
Funding: This work (1H-NMR measurement) was supported by the European Federation of Pharmaceutical Industries Associations(EFPIA), Innovative Medicines Initiative Joint Undertaking, EuropeanMedical Information Framework (EMIF) grant #115372 and the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme (grant #305507) “Heart ‘omics’ in AGEing” (HOMAGE). This study was further supported by the Strategic Research Funding from the University of Oulu, Finland, the Sigrid Juselius Foundation, the NovoNordisk Foundation, and the Academy of Finland (grant #294834). The serum NMR metabolomics platform has been supported by the Sigrid Juselius Foundation and the Strategic Research Funding from the University of Oulu. M.A.K.works in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_1201/1). V.S. was supported by the Finnish Foundation for Cardiovascular Research. N.J.R. was supported by the Glasgow Molecular Pathology NODE, funded by The Medical Research Council and The Engineering and Physical Sciences Research Council (MR/N005813/1, project code 69042/1).
Academy of Finland Grant Number: 294834
Detailed Information: 294834 (Academy of Finland Funding decision)
Copyright information: © 2017 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
  https://creativecommons.org/licenses/by/4.0/