{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:39:21Z","timestamp":1791067161024,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,4,18]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Differences in the clinical course of heritable thoracic aortic disease based on the disease\u2010causing gene have not been fully evaluated. To clarify the clinical relevance of causative genes in heritable thoracic aortic disease, we assessed the clinical course of patients categorized based on genetic diagnosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We investigated cardiovascular events and mortality in 518 genetically diagnosed patients in 4 groups: Group 1,\n              <jats:italic>FBN1<\/jats:italic>\n              (n=344); Group 2,\n              <jats:italic>TGFBR1<\/jats:italic>\n              ,\n              <jats:italic>TGFBR2<\/jats:italic>\n              ,\n              <jats:italic>SMAD3<\/jats:italic>\n              , or\n              <jats:italic>TGFB2<\/jats:italic>\n              (n=74); Group 3,\n              <jats:italic>COL3A1<\/jats:italic>\n              (n=60); and Group 4,\n              <jats:italic>ACTA2<\/jats:italic>\n              or\n              <jats:italic>MYH11<\/jats:italic>\n              (n=40). The median age at the first cardiovascular event ranged from 30.0 to 35.5\u2009years (\n              <jats:italic>P<\/jats:italic>\n              =0.36). Patients with gene variants related to transforming growth factor\u2010\u03b2 signaling had a significantly higher rate of subsequent events than those with\n              <jats:italic>FBN1<\/jats:italic>\n              variants (adjusted hazard ratio, 2.33 [95% CI, 1.60\u20133.38];\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Regarding the incidence of aortic dissection, there were no significant differences among the 4 groups in male patients (36.3%, 34.3%, 21.4%, and 54.2%, respectively;\n              <jats:italic>P<\/jats:italic>\n              =0.06). Female patients with\n              <jats:italic>COL3A1<\/jats:italic>\n              variants had a significantly lower incidence than female patients in the other 3 groups (34.2%, 59.0%, 3.1%, and 43.8%, respectively;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Gene variants related to transforming growth factor\u2010\u03b2 signaling are associated with a higher incidence of subsequent cardiovascular events than\n              <jats:italic>FBN1<\/jats:italic>\n              variants.\n              <jats:italic>COL3A1<\/jats:italic>\n              variants might be related to a lower incidence of aortic dissection than other gene variants in women only. Identifying the genetic background of patients with heritable thoracic aortic disease is important for determining appropriate treatment.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028625","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T09:11:06Z","timestamp":1681290666000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Association Between Genetic Diagnosis and Clinical Outcomes in Patients With Heritable Thoracic Aortic Disease"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-2644","authenticated-orcid":false,"given":"Takeshi","family":"Yagyu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Suita Japan"},{"name":"Department of Genomic Medicine National Cerebral and Cardiovascular Center Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5372-4932","authenticated-orcid":false,"given":"Teruo","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Suita Japan"},{"name":"Department of Genomic Medicine National Cerebral and Cardiovascular Center Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine National Cerebral and Cardiovascular Center Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4705-5207","authenticated-orcid":false,"given":"Kazufumi","family":"Ida","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine National Cerebral and Cardiovascular Center Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-376X","authenticated-orcid":false,"given":"Soshiro","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Research Institute Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-0949","authenticated-orcid":false,"given":"Kunihiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Research Institute Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery National Cerebral and Cardiovascular Center Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.089"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.570"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.009762"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043756"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001106"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu281"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00298-7"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072785"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.03.367"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.1009947"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_2_13_2","unstructured":"National Health and Nutrition Survey in Japan. 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