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Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012737","name":"Department of Health and Human","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when \u223c5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC\/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehad115","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T20:10:37Z","timestamp":1676923837000},"page":"2095-2110","source":"Crossref","is-referenced-by-count":55,"title":["Proteomic cardiovascular risk assessment in chronic kidney disease"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-2607","authenticated-orcid":false,"given":"Rajat","family":"Deo","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Electrophysiology Section, Perelman School of Medicine at the University of Pennsylvania , One Convention Avenue, Level 2 \/ City Side, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth F","family":"Dubin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd, Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin C","family":"Murthy","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Electrophysiology Section, Perelman School of Medicine at the University of Pennsylvania , One Convention Avenue, Level 2 \/ City Side, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochang","family":"Shou","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health , 615 N Wolfe St, Baltimore, MD 21205 , USA"},{"name":"Department of Medicine, Johns Hopkins University , 2024 E. Monument Street, Room 2-635, Suite 2-600, Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Grams","sequence":"additional","affiliation":[{"name":"Department of Epidemiology; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health , 615 N Wolfe St, Baltimore, MD 21205 , USA"},{"name":"Department of Medicine, Johns Hopkins University , 2024 E. Monument Street, Room 2-635, Suite 2-600, Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya L","family":"Surapaneni","sequence":"additional","affiliation":[{"name":"Department of Epidemiology; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health , 615 N Wolfe St, Baltimore, MD 21205 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeenat","family":"Bhat","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan , 5100 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-079X","authenticated-orcid":false,"given":"Jordana B","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , 215 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"},{"name":"Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania , 831 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Wearn Bldg. 3rd Floor. 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Francisco , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L","family":"Kimmel","sequence":"additional","affiliation":[{"name":"Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , 9000 Rockville Pike, Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran S","family":"Vasan","sequence":"additional","affiliation":[{"name":"Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine , Boston, MA , USA"},{"name":"Section of Cardiology, Department of Medicine, Boston University School of Medicine , Boston, MA , USA"},{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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