{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:29:20Z","timestamp":1790972960712,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,12,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">We recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)\u2013related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70\u00a0years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5\u2010year median follow\u2010up (maximal, 22.0\u00a0years), 283 incident CVDs occurred. Forty\u2010one proteins were significantly (false discovery rate &lt;0.05) related to the combined end point of incident CVD, with N\u2010terminal pro\u2013brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4\u2010disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0038).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Large\u2010scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.121.023330","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T14:12:49Z","timestamp":1638281569000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Large\u2010Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-8542","authenticated-orcid":false,"given":"Lars","family":"Lind","sequence":"first","affiliation":[{"name":"Department of Medical Sciences Uppsala University Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-1021","authenticated-orcid":false,"given":"Daniela","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Department of Medicine Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5466-8370","authenticated-orcid":false,"given":"Martin","family":"Ingelsson","sequence":"additional","affiliation":[{"name":"Department of Public Health and Caring Sciences\/Geriatrics Uppsala University Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-4637","authenticated-orcid":false,"given":"Johan","family":"\u00c4rnl\u00f6v","sequence":"additional","affiliation":[{"name":"Division of Family Medicine and Primary Care Department of Neurobiology, Care Sciences and Society Karolinska Institutet Huddinge Sweden"},{"name":"School of Health and Social Sciences Dalarna University Falun Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2349-0009","authenticated-orcid":false,"given":"Themistocles L.","family":"Assimes","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Department of Medicine Stanford University School of Medicine Stanford CA"},{"name":"Palo Alto VA Healthcare System Palo Alto CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312086"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0058-3"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13690-5"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315597"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0682-6"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.040180"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0175-2"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104476"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12453"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004801"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.002963"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017900"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.887521"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007634722658"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2004.12.007"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095192"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.106099"},{"key":"e_1_3_1_19_2","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal B","year":"2020","unstructured":"Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, Sidiropoulos K, Cook J, Gillespie M, Haw R, et al. 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