{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:10:14Z","timestamp":1778731814071,"version":"3.51.4"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8\u00b114.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%\u00b127.0% versus 50.4%\u00b138.7%; adjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, \u226575% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10\u20136.78];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26\u20137.24];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged \u226450 years (adjusted odds ratio, 4.08 [95% CI, 2.01\u20138.30];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319818","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T05:00:20Z","timestamp":1698901220000},"page":"300-313","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5452-4657","authenticated-orcid":true,"given":"Anne","family":"Cornelissen","sequence":"first","affiliation":[{"name":"CVPath Institute, Gaithersburg, MD (A.C., N.V.G., A.D., A.S., Y.S., R. Kawakami, M.M., K.K., R.F., S.K.B.G., R.B., B.A., R. Kutys, M.K., M.E.R., F.D.K., L.G., R.V., A.V.F.)."},{"name":"Department of Cardiology, University Hospital RWTH Aachen, Germany (A.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neel V.","family":"Gadhoke","sequence":"additional","affiliation":[{"name":"CVPath Institute, Gaithersburg, MD (A.C., N.V.G., A.D., A.S., Y.S., R. Kawakami, M.M., K.K., R.F., S.K.B.G., R.B., B.A., R. Kutys, M.K., M.E.R., F.D.K., L.G., R.V., A.V.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1158-8455","authenticated-orcid":true,"given":"Kathleen","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine, Baltimore (K.R., C.C.H., B.D.M., A.V.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chani J.","family":"Hodonsky","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville (C.J.H., C.L.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (R.M., N.A.B., T.D., M.L.G., N.S., D.E.A.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-7419","authenticated-orcid":true,"given":"Nathan A.","family":"Bihlmeyer","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (R.M., N.A.B., T.D., M.L.G., N.S., D.E.A.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9733-440X","authenticated-orcid":true,"given":"ThuyVy","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (R.M., N.A.B., T.D., M.L.G., N.S., D.E.A.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-2105","authenticated-orcid":true,"given":"Zhifen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Deutsches Herzzentrum M\u00fcnchen, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany (Z.C., H.S.)."},{"name":"Deutsches Zentrum f\u00fcr Herz-und Kreislauferkrankungen (DZHK), Partner Site Munich Heart Alliance, Germany (Z.C., H.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9099-2477","authenticated-orcid":true,"given":"Armelle","family":"Dikongue","sequence":"additional","affiliation":[{"name":"CVPath Institute, Gaithersburg, MD (A.C., N.V.G., A.D., A.S., Y.S., R. 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