Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Adverse Outcomes in Heart Failure.
| Title: | Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Adverse Outcomes in Heart Failure. |
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| Authors: | Vidula MK; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.).; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.).; Schurgers LJ; Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands (L.J.S.).; Zhao L; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Dib MJ; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.).; Zhao M; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.).; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.).; Wang Z; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Ebert C; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Salman O; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.).; Azzo JD; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.).; Zamani P; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.).; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.).; van Empel V; Department of Cardiology, Maastricht University Medical Center, Cardiovascular Research Institute Maastricht, the Netherlands (V.v.E.).; Richards AM; Cardiovascular Research Institute, National University of Singapore (A.M.R.).; Christchurch Heart Institute, University of Otago, New Zealand (A.M.R., R.D.).; Doughty R; Christchurch Heart Institute, University of Otago, New Zealand (A.M.R., R.D.).; Javaheri A; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO (A.J., D.L.M.).; Mann DL; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO (A.J., D.L.M.).; Rietzschell E; Department of Cardiovascular Diseases, Ghent University Hospital, Belgium (E.R.).; Kammerhoff K; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Schafer P; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Seiffert DA; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Ramirez-Valle F; Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.).; Cappola TP; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.).; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.).; Chirinos JA; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia (M.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.).; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.K.V., M.Z., O.S., J.D.A., P.Z., T.P.C., J.A.C.). |
| Source: | Circulation. Heart failure [Circ Heart Fail] 2026 Feb; Vol. 19 (2), pp. e012734. Date of Electronic Publication: 2026 Jan 28. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 101479941 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1941-3297 (Electronic) Linking ISSN: 19413289 NLM ISO Abbreviation: Circ Heart Fail Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Hagerstown, MD : Lippincott Williams & Wilkins |
| MeSH Terms: | Heart Failure*/blood ; Heart Failure*/mortality ; Heart Failure*/diagnosis ; Heart Failure*/physiopathology ; Extracellular Matrix Proteins*/blood ; Calcium-Binding Proteins*/blood; Biomarkers/blood ; Humans ; Male ; Matrix Gla Protein ; Female ; Middle Aged ; Aged ; Risk Factors ; Prognosis |
| Abstract: | Background: MGP (matrix Gla-protein), a known inhibitor of vascular calcification, becomes biologically active by vitamin K-dependent carboxylation. Circulating levels of dpucMGP (dephospho-uncarboxylated matrix Gla-protein), the inactive form of MGP, have been associated with large artery stiffening and reduced skeletal muscle mass in heart failure (HF). Whether dpucMGP is related to adverse outcomes in patients with HF is unknown.; Methods: In this cohort study, we measured plasma dpucMGP among 2247 PHFS (Penn HF Study) participants. We examined the relationship between dpucMGP and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with dpucMGP. We assessed the association between dpucMGP levels and (1) death or HF-related hospital admission; (2) all-cause death.; Results: Participants' median age was 61 years (interquartile range, 53-70 years), 64% were male, and 71% were White. dpucMGP exhibited prominent proteomic associations with acute phase response, coagulation, complement system, fibrosis, cell signaling, and metabolic pathways. Greater dpucMGP was associated with older age, renal dysfunction, and warfarin use, whereas Black ethnicity was associated with lower dpucMGP. Increased dpucMGP levels were associated with an increased risk of death or HF-related hospital admission (standardized hazard ratio, 1.23 [95% CI, 1.17-1.28]; P |
| Competing Interests: | Dr Chirinos is supported by National Institutes of Health (NIH) grants U01-TR003734, U01-TR003734-01S1, UO1-HL160277, R33-HL-146390, R01-HL153646, K24-AG070459, R01-AG058969, R01-HL157108, R01-HL155599, R01-HL104106, and R01HL155764. He has recently consulted for Bayer, Fukuda-Denshi, Bristol Myers Squibb, Biohaven Pharmaceuticals, Johnson & Johnson, Edwards Life Sciences, Merck, and NGM Biopharmaceuticals. He received University of Pennsylvania research grants from NIH, Fukuda-Denshi, Bristol Myers Squibb, Microsoft, and Abbott. He is named as inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction, and for the use of biomarkers in heart failure with preserved ejection fraction. He has received payments for editorial roles from the American Heart Association, the American College of Cardiology, Elsevier, and Wiley and payments for academic roles from the University of Texas, Boston University, and Virginia Commonwealth University. He has received research device loans from Atcor Medical, Fukuda-Denshi, Unex, Uscom, NDD Medical Technologies, Microsoft, and MicroVision Medical. Dr Schurgers is supported by Marie Skłodowska-Curie Actions–European Union grants ITN722609, ITN764474, and ITN813409. He has received grants from Gnosis by Lesaffre, Boehringer Ingelheim, and Bayer and consultancy fees from Immunodiagnostic Systems, not related to the submitted work. He is shareholder of Coagulation Profile BV. Dr Zamani is supported by R01 HL149722, R01 HL155599, R01 HL157264, U01-HL160277, and UH3 DK128298. Dr Zamani also receives research support from Amgen and the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania. He has consulted for Pfizer and Vyaire. Dr van Empel is supported by nonrestricted grants from Boehringer Ingelheim, Roche, Vifor Pharma, Pfizer, and AstraZeneca and consultancy fees from Boehringer Ingelheim, Novartis, Janssen, and Novo Nordisk, all paid to the institute, not related to the submitted work. The other authors report no conflicts. |
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| Grant Information: | R01 HL155599 United States HL NHLBI NIH HHS; K24 AG070459 United States AG NIA NIH HHS; R01 HL104106 United States HL NHLBI NIH HHS; R01 AG058969 United States AG NIA NIH HHS; R01 HL153646 United States HL NHLBI NIH HHS; R01 HL155764 United States HL NHLBI NIH HHS; U01 TR003734 United States TR NCATS NIH HHS; R01 HL157108 United States HL NHLBI NIH HHS; R01 HL157264 United States HL NHLBI NIH HHS; U01 HL160277 United States HL NHLBI NIH HHS; R01 HL149722 United States HL NHLBI NIH HHS; R01 HL088577 United States HL NHLBI NIH HHS; UH3 DK128298 United States DK NIDDK NIH HHS; R33 HL146390 United States HL NHLBI NIH HHS |
| Contributed Indexing: | Keywords: heart failure; vascular calcification; vitamin K; warfarin |
| Substance Nomenclature: | 0 (Matrix Gla Protein); 0 (Extracellular Matrix Proteins); 0 (Calcium-Binding Proteins); 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260128 Date Completed: 20260217 Latest Revision: 20260218 |
| Update Code: | 20260218 |
| PubMed Central ID: | PMC12854526 |
| DOI: | 10.1161/CIRCHEARTFAILURE.124.012734 |
| PMID: | 41603031 |
| Database: | MEDLINE |
Journal Article