{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:58:19Z","timestamp":1788350299952,"version":"build-2803163510"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"33","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SA 4598\/2-1"],"award-info":[{"award-number":["SA 4598\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["K12TR004381"],"award-info":[{"award-number":["K12TR004381"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Harvard Catalyst | The Harvard Clinical and Translational Science Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 [95% confidence interval 1.12\u20131.18], P &amp;lt; .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 [1.19\u20131.42], P &amp;lt; .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P &amp;lt; .0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaf891","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T12:00:00Z","timestamp":1761134400000},"page":"4593-4602","source":"Crossref","is-referenced-by-count":4,"title":["A polygenic risk score for peripheral artery disease and major adverse limb 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Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick K","family":"Kamanu","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P","family":"Giugliano","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D","family":"Wiviott","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M","family":"Scirica","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-2791","authenticated-orcid":false,"given":"Christopher P","family":"Cannon","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott M","family":"Antman","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , 60 Fenwood Rd, Suite 7022, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and 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