{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T21:35:55Z","timestamp":1773783355553,"version":"3.50.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>To investigate the proteomic signatures of heart failure (HF) in diabetes. The underlying mechanisms of the elevated risk of HF in diabetes are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>In 10\u2009189 ARIC study (Atherosclerosis Risk in Communities) participants free of HF (mean age 57\u00b17 years, 56% women, 22% Black adults, 14% with diabetes), we conducted discovery and internal validation for the associations of 4955 plasma proteins with HF by diabetes status. We performed (1) Cox regression to identify proteins associated with HF by diabetes status, (2) external validation in the MESA study (Multi-Ethnic Study of Atherosclerosis, n=5233, 633 with diabetes), and (3) pathway analyses for identified proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Over 24 years in ARIC, there were 2417 HF events (605 among individuals with diabetes). In 993 individuals with diabetes in the discovery sample, 19 proteins were associated with HF (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;10\n                      <jats:sup>\u20135<\/jats:sup>\n                      ), 12 proteins replicated in the internal validation sample (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05\/19). Six of the internally validated proteins replicated in MESA (false discovery rate, q&lt;0.05). Five proteins were specifically associated with HF in those with diabetes: 4 are novel (inactive tyrosine-protein kinase 7, chondroadherin, leucine-rich repeat, and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 and fibulin-5) and 1 is the previously known (cartilage intermediate layer protein 2). NPPB (N-terminal pro-BNP) was associated with HF in those with and without diabetes. Pathways over-represented among proteins associated with diabetes-related HF were lipid metabolism, inflammation, and brown adipose tissue (false discovery rate, q&lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We identified 5 proteomic markers (4 novel) uniquely related to HF risk among individuals with diabetes and not among those without diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.125.013171","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:02:24Z","timestamp":1769097744000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic Signatures of Cardiac Dysfunction Among People With Diabetes: The Atherosclerosis Risk in Communities Study"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-1617","authenticated-orcid":true,"given":"Justin B.","family":"Echouffo-Tcheugui","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes &amp; Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, MD (J.B.E.-T.)."},{"name":"Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.B.E.-T., J. Chen, M.R.R., K.M., E.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1603-282X","authenticated-orcid":true,"given":"Chiadi E.","family":"Ndumele","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (C.E.N., W.S.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingsha","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.B.E.-T., J. Chen, M.R.R., K.M., E.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-4848","authenticated-orcid":true,"given":"Mary R.","family":"Rooney","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.B.E.-T., J. Chen, M.R.R., K.M., E.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keenan A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD (K.A.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-0462","authenticated-orcid":true,"given":"Pascal","family":"Schlosser","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (P.S.)."},{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Germany (P.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7179-718X","authenticated-orcid":true,"given":"Kuni","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.B.E.-T., J. Chen, M.R.R., K.M., E.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-6023","authenticated-orcid":true,"given":"Morgan E.","family":"Grams","sequence":"additional","affiliation":[{"name":"Department of Medicine, New York University Grossman School of Medicine (M.E.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-1730","authenticated-orcid":true,"given":"Christie C.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Research, Baylor College of Medicine, Houston, TX (C.C.B., R.C.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2399-4653","authenticated-orcid":true,"given":"Ron C.","family":"Hoogeveen","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Research, Baylor College of Medicine, Houston, TX (C.C.B., R.C.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-0544","authenticated-orcid":true,"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, UTHealth School of Public Health, Houston, TX (E.B., B.Y.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-1077","authenticated-orcid":true,"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, UTHealth School of Public Health, Houston, TX (E.B., B.Y.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-4451","authenticated-orcid":true,"given":"Amil M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine (A.M.S.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0498-1980","authenticated-orcid":true,"given":"Ruth F.","family":"Dubin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine (R.F.D.), University of Texas Southwestern Medical Center, Dallas."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-2607","authenticated-orcid":true,"given":"Rajat","family":"Deo","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia (R.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-8633","authenticated-orcid":true,"given":"Yue","family":"Ren","sequence":"additional","affiliation":[{"name":"Data Science Core, University of Pennsylvania, Philadelphia (Y.R.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-1723","authenticated-orcid":true,"given":"Jerome I.","family":"Rotter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA (J.I.R., K.D.T)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2756-4370","authenticated-orcid":true,"given":"Kent D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA (J.I.R., K.D.T)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8655-5204","authenticated-orcid":true,"given":"Wendy S.","family":"Post","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (C.E.N., W.S.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-8882","authenticated-orcid":true,"given":"Peter","family":"Ganz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Zuckerberg San Francisco General Hospital and Department of Medicine, University of California, San Francisco (P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-7151","authenticated-orcid":true,"given":"Elizabeth","family":"Selvin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.B.E.-T., J. 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