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Proteomic Associations of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) in Heart Failure With Preserved Ejection Fraction.
Azzo, Joe David; Dib, Marie-Joe; Zagkos, Loukas; Zhao, Lei; Wang, Zhaoqing; Chang, Ching-Pin; Ebert, Christina; Salman, Oday; Gan, Sushrima; Zamani, Payman; Cohen, Jordana B; van Empel, Vanessa; Richards, A Mark; Javaheri, Ali; Mann, Douglas L; Rietzschel, Ernst R; Schafer, Peter H; Seiffert, Dietmar A; Gill, Dipender; Burgess, Stephen; Ramirez-Valle, Francisco; Gordon, David A; Cappola, Thomas P; Chirinos, Julio A.
Afiliação
  • Azzo JD; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.A., O.S., P.Z., T.P.C., J.A.C.).
  • Dib MJ; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.-J.D., S.G., P.Z., T.P.C., J.A.C.).
  • Zagkos L; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom (L.Z., D.G.).
  • Zhao L; 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.).
  • Wang Z; 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.).
  • Chang CP; 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.).
  • Ebert C; 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.).
  • Salman O; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.A., O.S., P.Z., T.P.C., J.A.C.).
  • Gan S; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.-J.D., S.G., P.Z., T.P.C., J.A.C.).
  • Zamani P; University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.A., O.S., P.Z., T.P.C., J.A.C.).
  • Cohen JB; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.-J.D., S.G., P.Z., T.P.C., J.A.C.).
  • van Empel V; 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.).
  • Richards AM; Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia (J.B.C.).
  • Javaheri A; Department of Cardiology, Maastricht University Medical Center, the Netherlands (V.v.E.).
  • Mann DL; Cardiovascular Research Institute, National University of Singapore (A.M.R.).
  • Rietzschel ER; Christchurch Heart Institute, University of Otago, Christchurch, CAN, New Zealand (A.M.R.).
  • Schafer PH; Washington University School of Medicine, St. Louis, MO (A.J., D.L.M.).
  • Seiffert DA; John J. Cochran Veterans Hospital, St. Louis, MO (A.J.).
  • Gill D; Washington University School of Medicine, St. Louis, MO (A.J., D.L.M.).
  • Burgess S; Department of Cardiovascular Diseases, Ghent University Hospital, Belgium (E.R.).
  • Ramirez-Valle F; 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.).
  • Gordon DA; 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.).
  • Cappola TP; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom (L.Z., D.G.).
  • Chirinos JA; Department of Public Health and Primary Care, University of Cambridge, United Kingdom (S.B.).
Circ Heart Fail ; 17(2): e011146, 2024 02.
Article em En | MEDLINE | ID: mdl-38299345
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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; ßTOPCAT=0.539; P<0.0001; ßPHFS=0.516; P<0.0001) and ANGPT2 (angiopoietin 2; ßTOPCAT=0.571; P<0.0001; ßPHFS=0.459; P<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.

CONCLUSIONS:

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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeo Natriurético Encefálico / Insuficiência Cardíaca Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Circ Heart Fail Assunto da revista: ANGIOLOGIA / CARDIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeo Natriurético Encefálico / Insuficiência Cardíaca Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Circ Heart Fail Assunto da revista: ANGIOLOGIA / CARDIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos