{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:15:21Z","timestamp":1792689321771,"version":"4.5.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We measured 4928 proteins using an aptamer-based proteomic assay (SOMAScan) in available plasma samples from 2 cohorts: (1) Participants with HFpEF enrolled in the PHFS (Penn Heart Failure Study; n=253); (2) TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) participants in the Americas (n=218). We assessed the relationship between SOMAScan-derived plasma NT-proBNP and levels of other proteins available in the SOMAScan assay version 4 using robust linear regression, with correction for multiple comparisons, followed by pathway analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      NT-proBNP levels exhibited prominent proteome-wide associations in PHFS and TOPCAT cohorts. Proteins most strongly associated with NT-proBNP in both cohorts included SVEP1 (sushi, von Willebrand factor type-A, epidermal growth factor, and pentraxin domain containing 1; \u03b2\n                      <jats:sub>TOPCAT<\/jats:sub>\n                      =0.539;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001; \u03b2\n                      <jats:sub>PHFS<\/jats:sub>\n                      =0.516;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001) and ANGPT2 (angiopoietin 2; \u03b2\n                      <jats:sub>TOPCAT<\/jats:sub>\n                      =0.571;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001; \u03b2\n                      <jats:sub>PHFS<\/jats:sub>\n                      =0.459;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001). Canonical pathway analysis demonstrated consistent associations with multiple pathways related to fibrosis and inflammation. These included hepatic fibrosis and inhibition of matrix metalloproteases. Analyses using cut points corresponding to estimated quantitative concentrations of 360 pg\/mL (and 480 pg\/mL in atrial fibrillation) revealed similar proteomic associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Circulating NT-proBNP levels exhibit prominent proteomic associations in HFpEF. Our findings suggest that higher NT-proBNP levels in HFpEF are a marker of fibrosis and inflammation. These findings will aid the interpretation of NT-proBNP levels in HFpEF and may guide the selection of participants in future HFpEF clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.123.011146","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T05:05:40Z","timestamp":1706763940000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Proteomic Associations of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"17","author":[{"given":"Joe David","family":"Azzo","sequence":"first","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.A., O.S., P.Z., T.P.C., J.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7591-5684","authenticated-orcid":true,"given":"Marie-Joe","family":"Dib","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.-J.D., S.G., P.Z., T.P.C., J.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7700-8102","authenticated-orcid":true,"given":"Loukas","family":"Zagkos","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom (L.Z., D.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-3712","authenticated-orcid":true,"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.-P.C., C.E., J.B.C., P.S., D.A.S., F.R.-V., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-4945","authenticated-orcid":true,"given":"Zhaoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.-P.C., C.E., J.B.C., P.S., D.A.S., F.R.-V., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Pin","family":"Chang","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.-P.C., C.E., J.B.C., P.S., D.A.S., F.R.-V., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Ebert","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.-P.C., C.E., J.B.C., P.S., D.A.S., F.R.-V., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8390-1036","authenticated-orcid":true,"given":"Oday","family":"Salman","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.A., O.S., P.Z., T.P.C., J.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrima","family":"Gan","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.-J.D., S.G., P.Z., T.P.C., J.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-5834","authenticated-orcid":true,"given":"Payman","family":"Zamani","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.A., O.S., P.Z., T.P.C., J.A.C.)."},{"name":"Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.-J.D., S.G., P.Z., T.P.C., J.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-079X","authenticated-orcid":true,"given":"Jordana B.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.-P.C., C.E., J.B.C., P.S., D.A.S., F.R.-V., D.A.G.)."},{"name":"Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia (J.B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-0296","authenticated-orcid":true,"given":"Vanessa","family":"van Empel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center, the Netherlands (V.v.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-8177","authenticated-orcid":true,"given":"A. 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