{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:24:27Z","timestamp":1781796267870,"version":"3.54.5"},"reference-count":33,"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":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>MGP (matrix Gla-protein), a known inhibitor of vascular calcification, becomes biologically active by vitamin K\u2013dependent 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>In this cohort study, we measured plasma dpucMGP among 2247 PHFS (Penn HF Study) participants. We examined the relationship between dpucMGP and \u22485000 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Participants\u2019 median age was 61 years (interquartile range, 53\u201370 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\u20131.28];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001) and all-cause death (standardized hazard ratio, 1.32 [95% CI, 1.25\u20131.40];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001), particularly among participants with nonischemic HF. Associations between dpucMGP and outcomes were dependent on warfarin use, and higher dpucMGP levels were found to mediate the association between warfarin use and adverse outcomes (death [total effect:\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.005; indirect effect:\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001] and death or HF-related hospital admission [total effect:\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001; indirect effect:\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Higher dpucMGP is associated with multiple biological pathways and with an increased risk for adverse outcomes in HF. Greater dpucMGP levels mediated the relationship between warfarin use and adverse outcomes. Further studies are required to determine the role of therapeutic interventions to reduce dpucMGP levels in this patient population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.124.012734","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:00:17Z","timestamp":1769594417000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Adverse Outcomes in Heart Failure"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-8757","authenticated-orcid":true,"given":"Mahesh K.","family":"Vidula","sequence":"first","affiliation":[{"name":"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.)."},{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7867-6957","authenticated-orcid":true,"given":"Leon J.","family":"Schurgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands (L.J.S.)."}],"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.E., K.K., P.S., D.A.S., F.R.-V.)."}],"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.K.V., M.-J.D., M.Z., P.Z., T.P.C., J.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"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.)."},{"name":"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.)."}],"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.E., K.K., P.S., D.A.S., F.R.-V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Ebert","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Company, Lawrenceville, NJ (L.Z., Z.W., C.E., K.K., P.S., D.A.S., F.R.-V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8390-1036","authenticated-orcid":true,"given":"Oday","family":"Salman","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8161-9611","authenticated-orcid":true,"given":"Joe D.","family":"Azzo","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-5834","authenticated-orcid":true,"given":"Payman","family":"Zamani","sequence":"additional","affiliation":[{"name":"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.)."},{"name":"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.)."}],"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, Cardiovascular Research Institute Maastricht, 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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