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      Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis

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          Abstract

          Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00–1.16; P = 0.04; I 2 = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61–3.96; P < 0.0001; I 2 = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04–1.47; P = 0.01; I 2 = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53–2.06; P < 0.00001; I 2 = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02–1.06; P = 0.003; I 2 = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.

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          Most cited references28

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          Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

          Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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            2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

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              A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.

              Over the past decade, myocardial structure, cardiomyocyte function, and intramyocardial signaling were shown to be specifically altered in heart failure with preserved ejection fraction (HFPEF). A new paradigm for HFPEF development is therefore proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations. The new paradigm presumes the following sequence of events in HFPEF: 1) a high prevalence of comorbidities such as overweight/obesity, diabetes mellitus, chronic obstructive pulmonary disease, and salt-sensitive hypertension induce a systemic proinflammatory state; 2) a systemic proinflammatory state causes coronary microvascular endothelial inflammation; 3) coronary microvascular endothelial inflammation reduces nitric oxide bioavailability, cyclic guanosine monophosphate content, and protein kinase G (PKG) activity in adjacent cardiomyocytes; 4) low PKG activity favors hypertrophy development and increases resting tension because of hypophosphorylation of titin; and 5) both stiff cardiomyocytes and interstitial fibrosis contribute to high diastolic left ventricular (LV) stiffness and heart failure development. The new HFPEF paradigm shifts emphasis from LV afterload excess to coronary microvascular inflammation. This shift is supported by a favorable Laplace relationship in concentric LV hypertrophy and by all cardiac chambers showing similar remodeling and dysfunction. Myocardial remodeling in HFPEF differs from heart failure with reduced ejection fraction, in which remodeling is driven by loss of cardiomyocytes. The new HFPEF paradigm proposes comorbidities, plasma markers of inflammation, or vascular hyperemic responses to be included in diagnostic algorithms and aims at restoring myocardial PKG activity. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                180006720@aston.ac.uk
                lijiahao218@gmail.com
                Journal
                Heart Fail Rev
                Heart Fail Rev
                Heart Failure Reviews
                Springer US (New York )
                1382-4147
                1573-7322
                6 February 2020
                6 February 2020
                2021
                : 26
                : 5
                : 1141-1150
                Affiliations
                [1 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, , Chinese University of Hong Kong, ; Hong Kong, SAR, People’s Republic of China
                [2 ]GRID grid.412648.d, ISNI 0000 0004 1798 6160, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, , Second Hospital of Tianjin Medical University, ; Tianjin, 300211 People’s Republic of China
                [3 ]GRID grid.452435.1, ISNI 0000 0004 1798 9070, Department of Cardiovascular Medicine, , The First Affiliated Hospital of Dalian Medical University, ; Dalian, China
                [4 ]GRID grid.411284.a, ISNI 0000 0004 4647 6936, Department of Clinical Research, , Federal University of Uberlândia, ; Uberlândia, Brazil
                [5 ]GRID grid.12955.3a, ISNI 0000 0001 2264 7233, Xiamen Cardiovascular Hospital, , Xiamen University, ; Xiamen, Fujian People’s Republic of China
                [6 ]GRID grid.7273.1, ISNI 0000 0004 0376 4727, Aston Medical School, , Aston University, ; Birmingham, UK
                [7 ]GRID grid.449813.3, ISNI 0000 0001 0305 0634, Wirral University Teaching Hospital NHS Foundation Trust, ; Arrowe Park Hospital, Arrowe Park Rd, Birkenhead, Wirral CH49 5PE UK
                Article
                9927
                10.1007/s10741-020-09927-x
                8310477
                32030562
                658cf324-2536-4e2c-bd7a-3ddb844f9fe4
                © The Author(s) 2020

                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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                Funding
                Funded by: Aston University
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2021

                Cardiovascular Medicine
                c-reactive protein,diastolic heart failure,hfpef,meta-analysis
                Cardiovascular Medicine
                c-reactive protein, diastolic heart failure, hfpef, meta-analysis

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