{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T10:19:08Z","timestamp":1777025948879,"version":"3.51.4"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis\/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH.<\/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              This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging\/magnetic resonance angiography imaging for evaluation of IASO (\u226550% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low\u2010density lipoprotein cholesterol level (240\u00b195 versus 244\u00b175\u2009mg\/dL;\n              <jats:italic>P<\/jats:italic>\n              =0.67) did not differ between the 2 groups. Despite the use of lipid\u2010lowering therapies (statin,\n              <jats:italic>P<\/jats:italic>\n              =0.71; high\u2010intensity statin,\n              <jats:italic>P<\/jats:italic>\n              =0.81; ezetimibe,\n              <jats:italic>P<\/jats:italic>\n              =0.33; proprotein convertase subxilisin\/kexin type 9 inhibitor,\n              <jats:italic>P<\/jats:italic>\n              =0.39; low\u2010density lipoprotein apheresis,\n              <jats:italic>P<\/jats:italic>\n              =0.14), on\u2010treatment low\u2010density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97\u00b162 versus 105\u00b150\u2009mg\/dL;\n              <jats:italic>P<\/jats:italic>\n              =0.17), accompanied by a higher triglyceride level (median, 109 versus 79\u2009mg\/dL;\n              <jats:italic>P<\/jats:italic>\n              =0.001). During the 12.4\u2010year observational period (interquartile range, 6.2\u201324.6\u2009years), asymptomatic IASO exhibited a 4.04\u2010fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71\u20139.55;\n              <jats:italic>P<\/jats:italic>\n              =0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71\u201310.9];\n              <jats:italic>P<\/jats:italic>\n              =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\">A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid\u2010lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH\u2010related atherosclerosis, which ultimately affects future outcomes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.033972","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T11:30:00Z","timestamp":1721129400000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Asymptomatic Intracranial Artery Stenosis\/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3673-4941","authenticated-orcid":false,"given":"Sayaka","family":"Funabashi","sequence":"first","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Japan"]},{"name":"Kyorin University Faculty of Medicine","place":["Mitaka, 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Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7271-2339","authenticated-orcid":false,"given":"Takahito","family":"Doi","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Morita","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0558-9323","authenticated-orcid":false,"given":"Eri","family":"Kiyoshige","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-0949","authenticated-orcid":false,"given":"Kunihiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5372-4932","authenticated-orcid":false,"given":"Teruo","family":"Noguchi","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Harada\u2010Shiba","sequence":"additional","affiliation":[{"name":"Osaka Medical and Pharmaceutical University","place":["Takatsuki, 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