{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T21:37:14Z","timestamp":1777844234272,"version":"3.51.4"},"posted":{"date-parts":[[2025,12,18]]},"group-title":"Cardiovascular Medicine","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Screening criteria for abdominal aortic aneurysm (AAA) are based on clinical factors, such as age and smoking history, but do not include biological factors that may better reflect disease pathogenesis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We sought to determine whether a proteomic risk score (ProRS) incorporating plasma protein abundance could improve prediction of AAA.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a cross-sectional analysis of nearly 37,000 participants in the UK Biobank Pharma Proteomics Project with plasma protein abundance data for 274 cardiometabolic proteins. ProRS models were developed using regularized regression.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The generated sparse ProRS contained well-established clinical risk factors as well as a single protein \u2013 matrix metalloproteinase 12 (MMP12). Overall performance and discriminatory utility of this model was higher than an identical model without MMP12 (difference in Brier score 2.1 \u00d7 10\n                    <jats:sup>-4<\/jats:sup>\n                    , 95% CrI 2.0-2.3 \u00d7 10\n                    <jats:sup>-4<\/jats:sup>\n                    ; difference in AUROC 0.021, 95% CrI 0.020 - 0.022). Within the cohort, current AAA screening recommendations applied to 4.6% of the population and captured 30% of cases, whereas screening 4.6% of the population at highest risk by ProRS captured 52% of cases. Among individuals with incident AAA, MMP12 abundance was independently associated with time to rupture or repair (HR 1.86, 95% CI 1.39\u20132.50, p &lt; 0.001). Additionally, MMP12 level improved discrimination of AAA in an external cohort (SIMPLER; difference in AUROC 0.084, 95% CrI 0.081 - 0.087).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A biologically-plausible ProRS incorporating a single matrix metalloproteinase improved prediction of AAA over clinical factors alone. These results may be used to enhance screening strategies for AAA.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.16.25341932","type":"posted-content","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T20:25:15Z","timestamp":1766089515000},"source":"Crossref","is-referenced-by-count":1,"title":["A sparse proteomic risk score incorporating plasma MMP12 level improves prediction of abdominal aortic aneurysm"],"prefix":"10.64898","author":[{"given":"Michael G.","family":"Clark","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna C.","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Levin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Woerner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dokyoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Damrauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025122206301002000_2025.12.16.25341932v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.10.044"},{"key":"2025122206301002000_2025.12.16.25341932v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.18928"},{"key":"2025122206301002000_2025.12.16.25341932v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2018.05.044"},{"key":"2025122206301002000_2025.12.16.25341932v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2021.11.022"},{"key":"2025122206301002000_2025.12.16.25341932v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2020.03.046"},{"key":"2025122206301002000_2025.12.16.25341932v1.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.052365"},{"key":"2025122206301002000_2025.12.16.25341932v1.7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.047544"},{"key":"2025122206301002000_2025.12.16.25341932v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01510-y"},{"key":"2025122206301002000_2025.12.16.25341932v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52452-w"},{"key":"2025122206301002000_2025.12.16.25341932v1.10","first-page":"425","article-title":"Predictive models for abdominal aortic aneurysms using polygenic scores and PheWAS-derived risk factors","volume":"28","year":"2023","journal-title":"Pac Symp Biocomput"},{"key":"2025122206301002000_2025.12.16.25341932v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2024.06.036"},{"key":"2025122206301002000_2025.12.16.25341932v1.12","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.10.25331242"},{"key":"2025122206301002000_2025.12.16.25341932v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2011.09.008"},{"key":"2025122206301002000_2025.12.16.25341932v1.14","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.037802"},{"key":"2025122206301002000_2025.12.16.25341932v1.15","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.20.24314065"},{"key":"2025122206301002000_2025.12.16.25341932v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586023-06592-6"},{"key":"2025122206301002000_2025.12.16.25341932v1.17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.120.007526"},{"key":"2025122206301002000_2025.12.16.25341932v1.18","doi-asserted-by":"publisher","DOI":"10.1175\/1520-0493(1950)078<0001:VOFEIT>2.0.CO;2"},{"key":"2025122206301002000_2025.12.16.25341932v1.19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2010.01523.x"},{"key":"2025122206301002000_2025.12.16.25341932v1.20","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.125.323057"},{"key":"2025122206301002000_2025.12.16.25341932v1.21","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.322096"},{"key":"2025122206301002000_2025.12.16.25341932v1.22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2182"},{"key":"2025122206301002000_2025.12.16.25341932v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2004.12.004"},{"key":"2025122206301002000_2025.12.16.25341932v1.24","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.008128"},{"key":"2025122206301002000_2025.12.16.25341932v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2016.12.030"},{"key":"2025122206301002000_2025.12.16.25341932v1.26","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2002.121124"},{"key":"2025122206301002000_2025.12.16.25341932v1.27","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000199268.27395.4f"},{"key":"2025122206301002000_2025.12.16.25341932v1.28","doi-asserted-by":"publisher","DOI":"10.1177\/107424840400900410"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.16.25341932","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:30:18Z","timestamp":1766413818000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2025.12.16.25341932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":28,"URL":"https:\/\/doi.org\/10.64898\/2025.12.16.25341932","relation":{},"subject":[],"published":{"date-parts":[[2025,12,18]]},"subtype":"preprint"}}