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      Serum Concentrations of Citrate, Tyrosine, 2- and 3- Hydroxybutyrate are Associated with Increased 3-Month Mortality in Acute Heart Failure Patients

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          Abstract

          Considering the already established relationship between the extent of the metabolic dysfunction and the severity of heart failure (HF), it is conceivable that the metabolomic profile of the serum may have a prognostic capacity for 3-month mortality in acute heart failure (AHF). Out of 152 recruited patients, 130 serum samples were subjected to the metabolomic analyses. The 3-month mortality rate was 24.6% (32 patients). Metabolomic profiling by nuclear magnetic resonance spectroscopy found that the serum levels of 2-hydroxybutyrate (2-HB), 3-hydoxybutyrate (3-HB), lactate, citrate, and tyrosine, were higher in patients who died within 3 months compared to those who were alive 3 months after onset of AHF, which was confirmed by univariable logistic regression analyses (p = 0.009, p = 0.005, p = 0.008, p<0.001, and p<0.001, respectively). These associations still remained significant for all tested metabolites except for lactate after adjusting for established prognostic parameters in HF. In conclusion, serum levels of 2-HB, 3-HB, tyrosine, and citrate measured at admission are associated with an increased 3-month mortality rate in AHF patients and might thus be of prognostic value in AHF.

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          ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

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            Trends in heart failure incidence and survival in a community-based population.

            The epidemic of heart failure has yet to be fully investigated, and data on incidence, survival, and sex-specific temporal trends in community-based populations are limited. To test the hypothesis that the incidence of heart failure has declined and survival after heart failure diagnosis has improved over time but that secular trends have diverged by sex. Population-based cohort study using the resources of the Rochester Epidemiology Project conducted in Olmsted County, Minnesota. Patients were 4537 Olmsted County residents (57% women; mean [SD] age, 74 [14] years) with a diagnosis of heart failure between 1979 and 2000. Framingham criteria and clinical criteria were used to validate the diagnosis Incidence of heart failure and survival after heart failure diagnosis. The incidence of heart failure was higher among men (378/100 000 persons; 95% confidence interval [CI], 361-395 for men; 289/100 000 persons; 95% CI, 277-300 for women) and did not change over time among men or women. After a mean follow-up of 4.2 years (range, 0-23.8 years), 3347 deaths occurred, including 1930 among women and 1417 among men. Survival after heart failure diagnosis was worse among men than women (relative risk, 1.33; 95% CI, 1.24-1.43) but overall improved over time (5-year age-adjusted survival, 43% in 1979-1984 vs 52% in 1996-2000, P<.001). However, men and younger persons experienced larger survival gains, contrasting with less or no improvement for women and elderly persons. In this community-based cohort, the incidence of heart failure has not declined during 2 decades, but survival after onset of heart failure has increased overall, with less improvement among women and elderly persons.
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              Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping.

              Proton nuclear magnetic resonance (NMR)-based metabolic phenotyping of urine and blood plasma/serum samples provides important prognostic and diagnostic information and permits monitoring of disease progression in an objective manner. Much effort has been made in recent years to develop NMR instrumentation and technology to allow the acquisition of data in an effective, reproducible, and high-throughput approach that allows the study of general population samples from epidemiological collections for biomarkers of disease risk. The challenge remains to develop highly reproducible methods and standardized protocols that minimize technical or experimental bias, allowing realistic interlaboratory comparisons of subtle biomarker information. Here we present a detailed set of updated protocols that carefully consider major experimental conditions, including sample preparation, spectrometer parameters, NMR pulse sequences, throughput, reproducibility, quality control, and resolution. These results provide an experimental platform that facilitates NMR spectroscopy usage across different large cohorts of biofluid samples, enabling integration of global metabolic profiling that is a prerequisite for personalized healthcare.
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                Author and article information

                Contributors
                tobias.madl@medunigraz.at
                sasa.frank@medunigraz.at
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                1 May 2019
                1 May 2019
                2019
                : 9
                : 6743
                Affiliations
                [1 ]ISNI 0000 0000 8988 2476, GRID grid.11598.34, Gottfried Schatz Research Center for Cell Signaling, , Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, ; Neue Stiftingtalstraße 6/6, 8010 Graz, Austria
                [2 ]ISNI 0000 0001 0657 4636, GRID grid.4808.4, University of Zagreb School of Medicine, ; Šalata 3, 10000 Zagreb, Croatia
                [3 ]ISNI 0000 0004 0397 9648, GRID grid.412688.1, University Hospital Centre Sisters of Charity, Department of Medicine, ; Vinogradska 29, 10000 Zagreb, Croatia
                [4 ]ISNI 0000 0004 0397 9648, GRID grid.412688.1, University Hospital Centre Zagreb, ; Kišpatićeva 12, 10000 Zagreb, Croatia
                [5 ]ISNI 0000 0000 8988 2476, GRID grid.11598.34, Institute for Medical Informatics, , Statistics und Documentation, Medical University of Graz, ; Auenbruggerplatz 2, 8036 Graz, Austria
                [6 ]GRID grid.452216.6, BioTechMed-Graz, ; Mozartgasse 12/II, 8010 Graz, Austria
                Author information
                http://orcid.org/0000-0002-9725-5231
                Article
                42937
                10.1038/s41598-019-42937-w
                6494857
                31043697
                63ffb2c2-be2c-4c67-9ae8-fe168a3c8d2f
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 August 2018
                : 12 April 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100002428, Austrian Science Fund (Fonds zur F&amp;#x00F6;rderung der Wissenschaftlichen Forschung);
                Award ID: P28854
                Award ID: I3792
                Award ID: P27166
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 31450110423
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100004955, &amp;#x00D6;sterreichische Forschungsf&amp;#x00F6;rderungsgesellschaft (Austrian Research Promotion Agency);
                Award ID: 864690
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                prognostic markers,heart failure,outcomes research
                Uncategorized
                prognostic markers, heart failure, outcomes research

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