{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:40:26Z","timestamp":1787704826545,"version":"build-2784847793"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; n\n                      <jats:sub>cases<\/jats:sub>\n                      =51\u2009929; n\n                      <jats:sub>controls<\/jats:sub>\n                      =39\u2009980) and subsequent arterial ischemic stroke (AIS; n\n                      <jats:sub>cases<\/jats:sub>\n                      =45\u2009120; n\n                      <jats:sub>controls<\/jats:sub>\n                      =46\u2009789) after the first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (protein quantitative trait loci) to determine the effect of 1463 plasma protein abundances on subsequent MACE using Mendelian randomization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Two variants were significantly associated with subsequent cardiovascular events: rs76472767 near gene\n                      <jats:italic toggle=\"yes\">RNF220<\/jats:italic>\n                      (odds ratio, 0.75 [95% CI, 0.64\u20130.85];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =3.69\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) with subsequent AIS and rs13294166 near gene\n                      <jats:italic toggle=\"yes\">LINC01492<\/jats:italic>\n                      (odds ratio, 1.52 [95% CI, 1.37\u20131.67];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =3.77\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) with subsequent MACE. Using Mendelian randomization, we identified 2 proteins with an effect on subsequent MACE after a stroke: CCL27 ([C-C motif chemokine 27], effect odds ratio, 0.77 [95% CI, 0.66\u20130.88]; adjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.05) and TNFRSF14 ([tumor necrosis factor receptor superfamily member 14], effect odds ratio, 1.42 [95% CI, 1.24\u20131.60]; adjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We found evidence that 2 proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.124.047103","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T14:01:06Z","timestamp":1721656866000},"page":"2045-2054","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank"],"prefix":"10.1161","volume":"55","author":[{"given":"Andrew R.","family":"Elmore","sequence":"first","affiliation":[{"name":"NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol, United Kingdom (A.R.E., A.E.H., G.H., K.T., T.R.G., G.D.S., L.P.)."},{"name":"MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, United Kingdom (A.R.E., A.E.H., G.H., K.T., T.R.G., G.D.S., L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimish","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Veteran\u2019s Affairs Healthcare System, Boston, MA (N.A., D.C.P., J.P.C., J.M.G., K.C., G.M.P.)."},{"name":"Department of Biostatistics, Boston University School of Public Health, MA (N.A., G.M.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April E.","family":"Hartley","sequence":"additional","affiliation":[{"name":"NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol, United Kingdom (A.R.E., A.E.H., G.H., K.T., T.R.G., G.D.S., L.P.)."},{"name":"MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, United Kingdom (A.R.E., A.E.H., G.H., K.T., T.R.G., G.D.S., 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