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Eur J Heart Fail. 2018 Apr;20(4):663-673. doi: 10.1002/ejhf.1076. Epub 2017 Dec 11.

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

Author information

1
Institute of Cardiovascular and Medical Sciences (ICAMS), BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
2
Glasgow Polyomics, Joseph Black Building, University of Glasgow, Glasgow, UK.
3
Robertson Centre for Biostatistics, Boyd Orr Building, University of Glasgow, Glasgow, UK.
4
Computational Medicine, Faculty of Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
5
NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
6
Leiden University Medical Centre, Leiden, The Netherlands.
7
Inserm Centre d'Investigation Clinique (CIC) 1443, Université de Lorraine, Lorraine, France.
8
Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Nancy, France.
9
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
10
Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
11
Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
12
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia.
13
National Institute for Health and Welfare (THL), Helsinki, Finland.
14
Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
15
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.

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.

KEYWORDS:

Advanced lipoprotein profiling; FINRISK; Heart failure; Metabolomics; PROSPER; Phenylalanine

Comment in

PMID:
29226610
PMCID:
PMC5947152
DOI:
10.1002/ejhf.1076
[Indexed for MEDLINE]
Free PMC Article

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