{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:52:47Z","timestamp":1791355967209,"version":"4.3.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">FXI (Factor XI) inhibitors have emerged as a promising antithrombotic strategy. However, a recent study linked decreased FXI levels with increased risk of heart failure (HF) and atrial fibrillation (AF), particularly in older adults. This study aims to investigate the associations of genetic FXI inhibition with cardiovascular events and cardiac function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This prospective study included 408\u2009642 UK Biobank participants of European ancestry. Two\n                      <jats:italic toggle=\"no\">F11<\/jats:italic>\n                      \u2010based genetic scores were constructed, weighted separately by their associations with activated partial thromboplastin time or circulating FXI levels. Adjusted Cox or linear regression models were built to predict incident HF, AF, and cardiac magnetic resonance measures. Interactions with age and age\u2010related cardiometabolic traits were tested.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Over 14.6\u2009years median follow\u2010up, 14\u2009451 participants developed incident HF, and 29\u2009243 developed incident AF. The FXI activated partial thromboplastin time score was not associated with HF, AF, or cardiac magnetic resonance measures overall. In exploratory interaction analyses, baseline hemoglobin A1c (HbA1c) modified its association with HF (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001) and AF (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.027), with higher HF risk observed among participants with HbA1c\u22657% (hazard ratio per 10% genetically predicted increase in activated partial thromboplastin time, 1.65 [95% CI, 1.13\u20132.40]) but not in those with HbA1c&lt;7%. No association was observed with AF across HbA1c strata. Similar patterns were observed for the FXI level score.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Genetically proxied FXI inhibition was not associated with HF, AF, or cardiac magnetic resonance\u2013derived cardiac measures overall, but its associations with HF and AF may be modified by HbA1c. Future studies are needed to verify these exploratory findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.126.051046","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:24:25Z","timestamp":1789737865000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Association of\n                    <i>F11<\/i>\n                    Gene Variants With Cardiovascular Events and Cardiac\u00a0Function"],"prefix":"10.1161","volume":"15","author":[{"given":"Qianxi","family":"Ye","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, College of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5264-6315","authenticated-orcid":false,"given":"Shengtao","family":"Hu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, College of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-7338","authenticated-orcid":false,"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, College of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"China Center for Health Development Studies","place":["Beijing, China"]},{"name":"Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1501-3303","authenticated-orcid":false,"given":"Yilin","family":"Lai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, College of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, College of 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