{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:02:31Z","timestamp":1787749351161,"version":"build-2784847793"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":60,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U01DK123013-03,R01 AG059729"],"award-info":[{"award-number":["U01DK123013-03,R01 AG059729"]}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["R01 AG059729,U01DK123013-03"],"award-info":[{"award-number":["R01 AG059729,U01DK123013-03"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Elevated lipoprotein(a) [Lp(a)] is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD). Although Lp(a) is a genetically determined risk factor, the plasma proteomic features associated with Lp(a) and whether they provide information about ASCVD risk beyond Lp(a) concentration are not well characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>We sought to identify plasma proteomic features associated with Lp(a) concentration and to evaluate whether an Lp(a)-associated proteomic signature is associated with ASCVD phenotypes in young, healthy adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In the Coronary Artery Risk Development in Young Adults (CARDIA) study, we measured year 7 Lp(a) and 184 cardiovascular proteins using the Olink proximity extension assay in 3,920 participants without prior coronary heart disease. Lp(a)-associated proteomic signatures were derived using least absolute shrinkage and selection operator (LASSO) regression in a split-sample design and tested for association with coronary artery calcification (CAC), incident coronary heart disease (CHD), and high-sensitivity C-reactive protein (hs-CRP) over 27 years of follow-up. External replication was performed in the UK Biobank (\n                      <jats:italic>n =<\/jats:italic>\n                      37,996).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Lp(a) was associated with CAC (OR 1.23 [1.13\u20131.34];\n                      <jats:italic>P &lt;<\/jats:italic>\n                      0.0001) and incident CHD (HR 1.23 [1.07\u20131.41];\n                      <jats:italic>P =<\/jats:italic>\n                      0.004). Lp(a) was correlated with proteomic features reflecting immune activation, coagulation, and vascular dysfunction. A quantitative Lp(a)-associated proteomics score was independently associated with incident CAC (standardized \u03b2 = 0.40,\n                      <jats:italic>P &lt;<\/jats:italic>\n                      0.0001) and hs-CRP (standardized \u03b2 = 0.11,\n                      <jats:italic>P =<\/jats:italic>\n                      0.00015) after adjustment for Lp(a) concentration. In the UK Biobank, a recalibrated Lp(a)-associated proteomics score was associated with CRP, incident CHD, and all-cause mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>In young adults, Lp(a) was associated with distinct proteomic features that independently predicted ASCVD phenotypes beyond Lp(a) concentration, generating hypotheses regarding biological pathways linked to Lp(a)-related cardiovascular risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>VA MERIT grant (1I01CX002560); Taubman Medical Research Institute (Wolfe Scholarship); National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK), NIH (U01DK123013-03); National Institute on Aging (NIA), NIH (R01AG059729); National Heart, Lung and Blood Institute (NHLBI), NIH (R01HL136685); American Heart Association Strategically Focused Research Network grant in Cardiometabolic Disease (funded proteomics in CARDIA); NIH (K23MD017253 and R01HL167733); Blue Cross Blue Shield of Michigan Foundation; A. Alfred Taubman Medical Research Institute; National Institute of Nursing Research (R01NR019628); National Institute of General Medical Sciences (NIGMS), NIH (R35-GM124836). The CARDIA study was conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (75N92023D00002 and 75N92023D00005), Northwestern University (75N92023D00004), University of Minnesota (75N92023D00006), and the Kaiser Foundation Research Institute (75N92023D00003).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ROLE OF FUNDING SOURCE<\/jats:title>\n                    <jats:p>The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci204287","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:38:22Z","timestamp":1776778702000},"source":"Crossref","is-referenced-by-count":1,"title":["Lipoprotein(a)-associated proteomic signature predicts cardiovascular disease in young adults"],"prefix":"10.1172","volume":"136","author":[{"given":"Sascha N.","family":"Goonewardena","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Division of Cardiovascular Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Yao","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Jurga","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Lloyd-Jones","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-6803","authenticated-orcid":true,"given":"Dilna","family":"Damodaran","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Thyagarajan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"David R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"University of Minnesota School of Public Health, Division of Epidemiology and Community Health, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Shore","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan, 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