{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021393550031744.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1161/circulationaha.120.045810"}},{"identifier":{"@type":"URI","@value":"https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.120.045810"}}],"dc:title":[{"@value":"Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction"}],"dcterms:alternative":[{"@value":"Results From the PROMIS-HFpEF Study"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n            <jats:title>Background:</jats:title>\n            <jats:p>A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Methods:</jats:title>\n            <jats:p>In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results:</jats:title>\n            <jats:p>\n              Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e′ ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%–35%), E/e′ ratio (18%–29%), tricuspid regurgitation velocity (27%–41%), and tricuspid annular plane systolic excursion (13%) (\n              <jats:italic>P</jats:italic>\n              <0.05 for all), but not right ventricular free wall strain. TNFR1 (tumor necrosis factor receptor 1), UPAR (urokinase plasminogen activator receptor), IGFBP7 (insulin-like growth factor binding protein 7), and GDF-15 (growth differentiation factor-15) were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:</jats:title>\n            <jats:p>Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.</jats:p>\n          </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021393550031757","@type":"Researcher","foaf:name":[{"@value":"Sandra Sanders-van Wijk"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.)."},{"@value":"Division of Cardiology, Department of Medicine, Maastricht University Medical Center, Netherlands (S.S.-v.W.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031747","@type":"Researcher","foaf:name":[{"@value":"Jasper Tromp"}],"jpcoar:affiliationName":[{"@value":"National Heart Centre Singapore & Duke-National University of Singapore (J.T., R.-S.T., C.S.P.L.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031751","@type":"Researcher","foaf:name":[{"@value":"Lauren Beussink-Nelson"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031745","@type":"Researcher","foaf:name":[{"@value":"Camilla Hage"}],"jpcoar:affiliationName":[{"@value":"Cardiology Unit and Heart and Vascular Theme, Karolinska Institutet, Department of Medicine, Stockholm, Sweden (C.H., L.H.L.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031746","@type":"Researcher","foaf:name":[{"@value":"Sara Svedlund"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Physiology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Sweden (S.S.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031755","@type":"Researcher","foaf:name":[{"@value":"Antti Saraste"}],"jpcoar:affiliationName":[{"@value":"Heart Center, Turku University Hospital and University of Turku, Finland (A.S.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031748","@type":"Researcher","foaf:name":[{"@value":"Stanley A. Swat"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031756","@type":"Researcher","foaf:name":[{"@value":"Cynthia Sanchez"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031749","@type":"Researcher","foaf:name":[{"@value":"Joyce Njoroge"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031758","@type":"Researcher","foaf:name":[{"@value":"Ru-San Tan"}],"jpcoar:affiliationName":[{"@value":"National Heart Centre Singapore & Duke-National University of Singapore (J.T., R.-S.T., C.S.P.L.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031753","@type":"Researcher","foaf:name":[{"@value":"Maria Lagerström Fermer"}],"jpcoar:affiliationName":[{"@value":"Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (M.L.F., L.-M.G.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031750","@type":"Researcher","foaf:name":[{"@value":"Li-Ming Gan"}],"jpcoar:affiliationName":[{"@value":"Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (M.L.F., L.-M.G.)."},{"@value":"Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Sweden (L.-M.G.)."},{"@value":"Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden (L.-M.G.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031752","@type":"Researcher","foaf:name":[{"@value":"Lars H. Lund"}],"jpcoar:affiliationName":[{"@value":"Cardiology Unit and Heart and Vascular Theme, Karolinska Institutet, Department of Medicine, Stockholm, Sweden (C.H., L.H.L.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031744","@type":"Researcher","foaf:name":[{"@value":"Carolyn S.P. Lam"}],"jpcoar:affiliationName":[{"@value":"National Heart Centre Singapore & Duke-National University of Singapore (J.T., R.-S.T., C.S.P.L.)."}]},{"@id":"https://cir.nii.ac.jp/crid/1380021393550031754","@type":"Researcher","foaf:name":[{"@value":"Sanjiv J. Shah"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.S.-v.W., L.B.-N., S.A.S., C.S., J.N., S.J.S.)."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00097322"},{"@type":"EISSN","@value":"15244539"}],"prism:publicationName":[{"@value":"Circulation"}],"dc:publisher":[{"@value":"Ovid Technologies (Wolters Kluwer Health)"}],"prism:publicationDate":"2020-11-24","prism:volume":"142","prism:number":"21","prism:startingPage":"2029","prism:endingPage":"2044"},"reviewed":"false","url":[{"@id":"https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.120.045810"}],"createdAt":"2020-10-09","modifiedAt":"2024-05-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360865816798487808","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Vitamin D Levels in Black Americans and the Association With Left Ventricular Remodeling and Incident Heart Failure With Preserved Ejectin Fraction: The Jackson Heart Study"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1161/circulationaha.120.045810"},{"@type":"CROSSREF","@value":"10.1016/j.cardfail.2022.07.049_references_DOI_Vzy8TzCPn7rardgWKywqYaCjHrf"}]}