{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:08:05Z","timestamp":1789553285878,"version":"build-2803163510"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">We investigated whether circulating angiotensinogen levels are associated with the risk of ischemic stroke and examined sex\u2010specific differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We included 5622 participants (mean age, 62.7\u2009years; 52% women) free of cardiovascular disease at baseline (2000\u20132002) and followed them through 2020. Cox models assessed the association between angiotensinogen and ischemic stroke, including sex\u2010stratified hazard ratios (HRs) with 95% CIs. Mediation analyses estimated the contribution of risk factors to observed associations. Subgroup analyses with multiplicative interaction testing were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      During follow\u2010up, 283 ischemic stroke events occurred. Each 1\u2010SD increase in log\u2010transformed angiotensinogen was associated with a 16% higher stroke risk (HR, 1.16 [95% CI, 1.00\u20131.34]). Significant interaction with sex was observed (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      interaction&lt;0.001). In men, angiotensinogen showed a positive dose\u2013response association with ischemic stroke (adjusted HR per SD increase, 1.71 [95% CI, 1.33\u20132.19]). Compared with the lowest tertile (&lt;16.8\u2009\u03bcg\/mL), adjusted HRs were 1.68 (95% CI, 1.08\u20132.61) and 1.95 (95% CI, 1.26\u20133.03) for the second and third (&gt;20\u2009\u03bcg\/mL) tertiles, respectively (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      trend=0.004). Diabetes marginally mediated the association in men (proportion mediated, 0.04 [95% CI, 0.00\u20130.15]). Significant evidence of an association between angiotensinogen and ischemic stroke in women was not observed (HR, 1.07 [95% CI, 0.88\u20131.29] per SD). No significant multiplicative interactions were observed across subgroups defined by age, race, smoking status, diabetes, obesity, angiotensin\u2010converting enzyme inhibitor\/angiotensin II receptor blocker use, hypertension, chronic kidney disease, and high\u2010sensitivity C\u2010reactive protein levels in either sex after Bonferroni correction (all\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      interaction&gt;0.002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Higher circulating angiotensinogen levels are associated with an increased risk of ischemic stroke in men, independent of blood pressure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047698","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:13:19Z","timestamp":1781525599000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Blood Levels of Angiotensinogen and Risk of Ischemic Stroke: The Multi\u2010Ethnic Study of Atherosclerosis"],"prefix":"10.1161","volume":"15","author":[{"given":"Soroush","family":"Masrouri","sequence":"first","affiliation":[{"name":"Shahid Beheshti University of Medical Sciences","place":["Tehran, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-9716","authenticated-orcid":false,"given":"Patrick J.","family":"Trainor","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, USA"]},{"name":"University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4084-8175","authenticated-orcid":false,"given":"Parag Anilkumar","family":"Chevli","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine","place":["Winston\u2010Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8756-6995","authenticated-orcid":false,"given":"Jo\u00e3o A.C.","family":"Lima","sequence":"additional","affiliation":[{"name":"Johns Hopkins University","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-9494","authenticated-orcid":false,"given":"Sotirios","family":"Tsimikas","sequence":"additional","affiliation":[{"name":"University of California\u2013San Diego","place":["La Jolla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-9748","authenticated-orcid":false,"given":"Andrew P.","family":"DeFilippis","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-3287","authenticated-orcid":false,"given":"Michael D.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine","place":["Winston\u2010Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2022.06.005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.124.318374"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs075"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(03)14282-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f360"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.176636"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.111119"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12703"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2021.04.004"},{"key":"e_1_3_2_11_2","unstructured":"Desai S. 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