{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:11:23Z","timestamp":1793452283815,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment\u2010resistant disorder characterized by early\u2010onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain.<\/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                      Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a \u201creal\u2010world\u201d setting. Untreated low\u2010density lipoprotein cholesterol levels were lower in adults than children (533 versus 776\u2009mg\/dL;\n                      <jats:italic>P<\/jats:italic>\n                      =0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow\u2010up, despite multiple lipid\u2010lowering treatment, low\u2010density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid\u2010lowering treatments were prescribed for 18%; 40% were on no lipid\u2010lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid\u2010lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.029175","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T06:57:24Z","timestamp":1682751444000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-3824","authenticated-orcid":false,"given":"Marina","family":"Cuchel","sequence":"first","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3846-843X","authenticated-orcid":false,"given":"Paul C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C.","family":"Hudgins","sequence":"additional","affiliation":[{"name":"The Rogosin Institute\/Weill Cornell Medical College New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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