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      Dynamics of growth differentiation factor 15 in acute heart failure

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          Abstract

          Aims

          Risk stratification in acute heart failure (HF) patients can help to decide therapies and time for discharge. The potential of growth differentiation factor 15 (GDF‐15) in HF has been previously shown. We aimed to study the importance of GDF‐15‐level variations in acute HF patients.

          Methods and results

          We retrospectively evaluated a cohort of patients hospitalized due to acute HF. GDF‐15 was measured both at admission and on the discharge day. Patients were followed‐up during a 3 year period. The endpoint under analysis was all‐cause mortality. GDF‐15 variation is equal to [(admission GDF‐15 − discharge GDF‐15)∕admission GDF‐15] × 100. Variation was categorized in levels of increase or decrease of GDF‐15. Patients were cross‐classified according to admission and discharge GDF‐15 cut‐off points. A Cox regression analysis was used to assess the prognostic impact of GDF‐15 variation and the impact of both admission and discharge GDF‐15 according to the cross‐classification. We studied a group of 249 patients with high co‐morbidity burden. Eighty‐one patients died at 1 year and 147 within 3 years. There was a modest decrease in GDF‐15 during hospitalization from a median value of 4087 to 3671 ng/mL ( P = 0.02). No association existed between GDF‐15 variation and mortality. In multivariate analysis, patients with admission GDF‐15 ≥ 3500 ng/mL and discharge GDF‐15 ≥ 3000 ng/mL had a significantly higher 1 year death risk when compared with the remaining—hazard ratio = 2.59 (95% confidence interval: 1.41–4.76)—and a 3 year 1.76 (95% confidence interval: 1.08–2.87) higher death risk compared with those with both values below the cut‐off.

          Conclusions

          Growth differentiation factor 15 decreased during an acute HF hospitalization, but its variation had no prognostic implications. The knowledge of both admission and discharge GDF‐15 added meaningful information to patients' risk stratification.

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          Most cited references33

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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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            Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease.

            Growth differentiation factor 15 (GDF-15) is expressed and secreted in response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation. Cardiovascular (CV) disease is a major driver of GDF-15 production. GDF-15 has favorable preanalytic characteristics and can be measured in serum and plasma by immunoassay.
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              Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure.

              We explored the prognostic utility of growth differentiation factor (GDF)-15 in patients with chronic heart failure (CHF). Growth differentiation factor-15 is a stress-responsive member of the transforming growth factor-beta cytokine superfamily. It has recently been observed that patients with CHF have increased circulating levels of GDF-15. The relations of GDF-15 to other biomarkers and to mortality in CHF have never been studied. Circulating levels of GDF-15 were determined by immunoradiometric assay in 455 patients with CHF with a median left ventricular ejection fraction (LVEF) of 32% (interquartile range 25% to 39%). The median GDF-15 level was 1,949 ng/l (interquartile range 1,194 to 3,577); 74.9% of the patients presented with GDF-15 levels >1,200 ng/l, the upper limit of normal in healthy elderly individuals. The GDF-15 levels were closely related to New York Heart Association (NYHA) functional class and to amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The risk of death during follow-up increased with increasing quartiles of GDF-15. Mortality rates at 48 months were 10.0%, 9.4%, 33.4%, and 56.2% in the respective quartiles (p < 0.001). After adjustment for clinical variables and established biomarkers of adverse prognosis, including NT-proBNP, renal dysfunction, anemia, and hyperuricemia, GDF-15 remained an independent predictor of mortality (adjusted hazard ratio for 1 U in the Ln scale 2.26; 95% confidence interval 1.52 to 3.37; p < 0.001). Growth differentiation factor 15 provided prognostic information in clinically relevant patient subgroups (defined according to age, body mass index, heart failure etiology, concomitant medical therapy, renal function, and the levels of hemoglobin and uric acid) and added prognostic information to NYHA functional class, LVEF, and NT-proBNP. Growth differentiation factor 15 is a new biomarker of the risk of death in patients with CHF that provides prognostic information beyond established clinical and biochemical markers.
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                Author and article information

                Contributors
                pbettfer@med.up.pt
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                02 May 2021
                August 2021
                : 8
                : 4 ( doiID: 10.1002/ehf2.v8.4 )
                : 2527-2534
                Affiliations
                [ 1 ] Internal Medicine Department Centro Hospitalar Universitário São João Porto Portugal
                [ 2 ] Heart Failure Clinic of the Internal Medicine Department Centro Hospitalar Universitário São João Porto Portugal
                [ 3 ] Cardiovascular R&D Unit (UnIC) University of Porto Porto Portugal
                [ 4 ] Faculty of Medicine University of Porto Alameda Professor Hernâni Monteiro Porto 4200‐319 Portugal
                [ 5 ] Endocrinology Department Centro Hospitalar do Tâmega e Sousa Penafiel Portugal
                [ 6 ] EPIUnit—Instituto de Saúde Pública Universidade do Porto Porto Portugal
                [ 7 ] Serviço de Medicina Interna Hospital CUF Porto Porto Portugal
                [ 8 ] Clinical Pathology Department Centro Hospitalar Universitário São João Porto Portugal
                Author notes
                [*] [* ]Correspondence to: Paulo Bettencourt, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200‐319 Porto, Portugal. Tel: +351919875957. Email: pbettfer@ 123456med.up.pt
                Article
                EHF213377 ESCHF-21-00008
                10.1002/ehf2.13377
                8318469
                33938154
                366df322-f8e3-4c2c-8fa9-4490ec456fd9
                © 2021 The Authors. ESC 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 http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 21 March 2021
                : 09 January 2021
                : 08 April 2021
                Page count
                Figures: 4, Tables: 3, Pages: 8, Words: 3337
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                August 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.4 mode:remove_FC converted:28.07.2021

                heart failure,growth differentiation factor 15,prognosis

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