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
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Publish Date: | 2018-08-23 |
Description: |
AbstractAims: 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. see all
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Series: |
European journal of heart failure |
ISSN: | 1388-9842 |
ISSN-E: | 1879-0844 |
ISSN-L: | 1388-9842 |
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 General medicine, internal medicine and other clinical 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/ |