{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:40:58Z","timestamp":1787240458237,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Low-dose aspirin is no longer recommended for routine primary prevention in older adults due to bleeding risks outweighing vascular benefits. We hypothesized that an integrative polygenic score (iPGS) could identify a subgroup of older individuals who derive net benefit from aspirin for the primary prevention of ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We performed post hoc analysis of the ASPREE randomized, placebo-controlled trial (Aspirin in Reducing Events in the Elderly) of daily 100-mg aspirin, in 12\u2009031 genotyped participants of European ancestry aged &gt;70 years without prior cardiovascular disease. The iPGS was derived from &gt;1.2 million variants and evaluated both continuously and by quintiles. Cox models assessed associations between polygenic risk, ischemic stroke, and major bleeding events, and tested the interaction between the iPGS and treatment allocation, with adjustment for baseline lifestyle and clinical covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The mean age of participants was 75.1 years, and 54.9% were women. Over a median of 4.6 years, 187 ischemic strokes and 373 major bleeds occurred, including 101 intracranial bleeds (46 hemorrhagic strokes). Each 1-SD increase in the iPGS was associated with higher incident ischemic stroke risk (hazard ratio, 1.39 [95% CI, 1.20\u20131.62]). An interaction between the continuous iPGS and aspirin allocation was observed for ischemic stroke (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04) but not major bleeding. In the highest iPGS quintile, aspirin reduced ischemic stroke by 51% (hazard ratio, 0.49 [95% CI, 0.28\u20130.85]) without significantly increasing major bleeding (hazard ratio, 1.15 [95% CI, 0.71\u20131.88]). No benefit was observed in the overall cohort or in lower-risk quintiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Among older adults, high polygenic risk identifies individuals who may experience substantial stroke reduction with aspirin, with no excess bleeding. These findings raise the possibility that genomic risk stratification may enable targeted aspirin use for the primary prevention of ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT01038583.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.054979","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T09:00:43Z","timestamp":1778230843000},"page":"2098-2107","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Polygenic Risk Identifies Older Adults Who May Benefit From Aspirin for the Primary Prevention of Ischemic Stroke"],"prefix":"10.1161","volume":"57","clinical-trial-number":[{"clinical-trial-number":"nct01038583","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-2779","authenticated-orcid":true,"given":"Chenglong","family":"Yu","sequence":"first","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."},{"name":"Victorian Heart Institute (C.Y.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7894-2485","authenticated-orcid":true,"given":"Sultana Monira","family":"Hussain","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3515-0557","authenticated-orcid":true,"given":"Peter D.","family":"Fransquet","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3997-6118","authenticated-orcid":true,"given":"Cammie","family":"Tran","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5291-0610","authenticated-orcid":true,"given":"Andrew M.","family":"Tonkin","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-7161","authenticated-orcid":true,"given":"Mark R.","family":"Nelson","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."},{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia (M.R.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-3944","authenticated-orcid":true,"given":"Christopher M.","family":"Reid","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."},{"name":"School of Population Health, Curtin University, Perth, Western Australia, Australia (C.M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-2757","authenticated-orcid":true,"given":"Johannes T.","family":"Neumann","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."},{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, Germany (J.T.N.)."},{"name":"German Center for Cardiovascular Research (DZHK), Hamburg, Germany (J.T.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff D.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (J.D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7723-9461","authenticated-orcid":true,"given":"Charles B.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Department of Epidemiology, Brown University, Providence, RI (C.B.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hand","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine (P.H., A.B., G.C.C.), Monash University, Melbourne, Victoria, Australia."},{"name":"Stroke Unit, Department of Neurology, The Alfred Hospital, Melbourne, Victoria, Australia (P.H., G.C.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-3403","authenticated-orcid":true,"given":"Geoffrey A.","family":"Donnan","sequence":"additional","affiliation":[{"name":"Melbourne Brain Centre, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia (G.A.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9466-2862","authenticated-orcid":true,"given":"Amy","family":"Brodtmann","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine (P.H., A.B., G.C.C.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-6907","authenticated-orcid":true,"given":"Geoffrey C.","family":"Cloud","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine (P.H., A.B., G.C.C.), Monash University, Melbourne, Victoria, Australia."},{"name":"Stroke Unit, Department of Neurology, The Alfred Hospital, Melbourne, Victoria, Australia (P.H., G.C.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1049-5129","authenticated-orcid":true,"given":"John J.","family":"McNeil","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0902-6798","authenticated-orcid":true,"given":"Paul","family":"Lacaze","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine (C.Y., S.M.H., P.D.F., C.T., A.M.T., M.R.N., C.M.R., J.T.N., J.J.M., P.L.), Monash University, Melbourne, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2021.100256"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.17038"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy813"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.20578"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805819"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804988"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31924-X"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.25803"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaf329"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024436"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13848-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05165-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.07.027"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacadv.2023.100754"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvae085"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800722"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803955"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.120.033670"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12206491"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308441"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.07.015"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000116869.64771.5A"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.019653"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11318-1"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009584"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000014872"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00783-5"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.121.003429"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.125.054979","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T19:37:44Z","timestamp":1785958664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.125.054979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1161\/STROKEAHA.125.054979"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.125.054979","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}