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      Novel Urinary Peptidomic Classifier Predicts Incident Heart Failure

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          Abstract

          Background

          Detection of preclinical cardiac dysfunction and prognosis of left ventricular heart failure ( HF) would allow targeted intervention, and appears to be the most promising approach in its management. Novel biomarker panels may support this approach and provide new insights into the pathophysiology.

          Methods and Results

          A retrospective comparison of urinary proteomic profiles generated by mass spectrometric analysis from 49 HF patients, 36 patients who progressed to HF within 2.6±1.6 years, and 192 sex‐ and age‐matched controls who did not progress to HF enabled identification of 96 potentially HF‐specific peptide biomarkers. Based on these 96 peptides, the classifier called Heart Failure Predictor ( HFP) was established by support vector machine modeling. The incremental prognostic value of HFP was subsequently evaluated in urine samples from 175 individuals with asymptomatic diastolic dysfunction from an independent population cohort. Within 4.8 years, 17 of these individuals progressed to overt HF. The area under receiver‐operating characteristic curve was 0.70 (95% CI, 0.56–0.82); P=0.0047 for HFP and 0.57 (0.42–0.72; P=0.62) for N‐terminal pro b‐type natriuretic peptide. Hazard ratios were 1.63 ( CI, 1.04–2.55; P=0.032) per 1‐ SD increment in HFP and 0.70 ( CI, 0.35–1.41; P=0.32) for a doubling of the logarithmically transformed N‐terminal pro b‐type natriuretic peptide.

          Conclusions

          HFP is a novel biomarker derived from the urinary proteome and might serve as a sensitive tool to improve risk stratification, patient management, and understanding of the pathophysiology of HF.

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          Most cited references27

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

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              Cardiac interstitium in health and disease: the fibrillar collagen network.

              Composed of type I and III collagens, the valve leaflets, chordae tendineae and collagen matrix of the myocardium form a structural continuum. Synthesized by cardiac fibroblasts, these fibrillar collagens support and tether myocytes to maintain their alignment, whereas their respective tensile strength and resilience resist the deformation, maintain the shape and thickness, prevent the rupture and contribute to the passive and active stiffness of the myocardium. An acquired or congenital defect in this collagen network can lead to abnormalities in myocardial architecture, mechanics or valve function. In the hypertrophic process that accompanies a pressure overload, for example, increased collagen synthesis, fibroblast proliferation and a structural and biochemical remodeling of the matrix are seen. This includes distinctive patterns of reparative and reactive myocardial fibrosis, each of which alters diastolic and systolic myocardial stiffness and may lead to pathologic hypertrophy. Alternatively, a loss of collagen tethers or decline in matrix tensile strength can be responsible for regional or global transformations in myocardial architecture and function seen in the reperfused ("stunned") myocardium and in dilated (idiopathic) cardiopathy. Inherited disorders in the transcriptional and posttranslational processing of collagen can also alter the biophysical properties of the network. Future studies into collagen gene regulation, gene switching events and the control of collagen synthesis and degradation are needed to develop a more complete understanding of the relation between the collagen network and acquired and inherited forms of heart disease and to utilize therapeutics that will prevent, retard or regress abnormal collagen matrix remodeling.
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                Author and article information

                Contributors
                jan.staessen@med.kuleuven.be , ja.staessen@maastrichtuniversity.nl
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                07 August 2017
                August 2017
                : 6
                : 8 ( doiID: 10.1002/jah3.2017.6.issue-8 )
                Affiliations
                [ 1 ] Studies Coordinating Centre Research Unit Hypertension and Cardiovascular Epidemiology KU Leuven Department of Cardiovascular Sciences University of Leuven Belgium
                [ 2 ] Program of Cardiovascular Diseases Centre for Applied Medical Research Navarra Institute for Health Research University of Navarra Pamplona Spain
                [ 3 ] CIBERCV Carlos III Institute of Health Madrid Spain
                [ 4 ] Mosaiques Diagnostics and Therapeutics AG Hanover Germany
                [ 5 ] Generation Scotland Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh United Kingdom
                [ 6 ] Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom
                [ 7 ] R & D Group VitaK Maastricht University Maastricht The Netherlands
                Author notes
                [*] [* ] Correspondence to: Jan A. Staessen, MD, PhD, Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Box 7001, BE‐3000 Leuven, Belgium. E‐mail: jan.staessen@ 123456med.kuleuven.be or ja.staessen@ 123456maastrichtuniversity.nl
                Article
                JAH32395
                10.1161/JAHA.116.005432
                5586413
                28784649
                bf1793a3-9b5b-4c01-a47c-2bed97280e1c
                © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Figures: 3, Tables: 3, Pages: 11, Words: 7767
                Product
                Funding
                Funded by: European Union
                Award ID: HEALTH‐F7‐278249
                Award ID: HEALTH‐F7‐305507
                Funded by: Chief Scientist Office of the Scottish Government Health Directorates
                Award ID: CZD/16/6
                Funded by: Scottish Funding Council
                Award ID: HR03006
                Funded by: Ministry of Economy and Competitiveness
                Funded by: Carlos III Institute of Health
                Award ID: CB16/11/00483
                Funded by: European Research Council
                Award ID: 2011‐294713‐EPLORE
                Award ID: 713601‐uPROPHET
                Funded by: Fonds voor Wetenschappelijk Onderzoek Vlaanderen
                Funded by: Ministry of the Flemish Community
                Award ID: G.0881.13
                Award ID: G.088013
                Award ID: 11Z0916N
                Categories
                Original Research
                Original Research
                Heart Failure
                Custom metadata
                2.0
                jah32395
                August 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.7 mode:remove_FC converted:24.08.2017

                Cardiovascular Medicine
                biomarker,heart failure,proteomics,risk stratification,prognosis,biomarkers
                Cardiovascular Medicine
                biomarker, heart failure, proteomics, risk stratification, prognosis, biomarkers

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