{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:00:56Z","timestamp":1787504456164,"version":"build-2736575974"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,7,25]]},"abstract":"\n Background:<\/jats:title>\n Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Children with HeFH (age, 6\u2013<18 years) and low-density lipoprotein cholesterol >4.9 mmol\/L or >4.1 mmol\/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6\u2013<10 years) or 20 mg (age, 10\u2013<18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings.\n P<\/jats:italic>\n values were adjusted for age, sex, carotid artery site, and family relations.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n At baseline, mean\u00b1SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397\u00b10.049 and 0.377\u00b10.045 mm, respectively;\n P<\/jats:italic>\n =0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm\/y (95% confidence interval, 0.0030\u20130.0082) in children with HeFH and 0.0143 mm\/y (95% confidence interval, 0.0095\u20130.0192) in unaffected siblings (\n P<\/jats:italic>\n =0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408\u00b10.043 and 0.402\u00b10.042 mm, respectively;\n P<\/jats:italic>\n =0.2).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n In children with HeFH who were \u22656 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration:<\/jats:title>\n \n URL:\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier: NCT01078675.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.116.025158","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T21:10:23Z","timestamp":1496869823000},"page":"359-366","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"136","author":[{"given":"Marjet J.A.M.","family":"Braamskamp","sequence":"first","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisle","family":"Langslet","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"McCrindle","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cassiman","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon A.","family":"Francis","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Gagne","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gaudet","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M.","family":"Morrison","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Wiegman","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci","family":"Turner","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elinor","family":"Miller","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Meeike","family":"Kusters","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Raichlen","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Martin","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan A.","family":"Stein","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.P.","family":"Kastelein","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Hutten","sequence":"additional","affiliation":[{"name":"From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"e_1_3_4_3_2","first-page":"2863","volume-title":"In: The Metabolic and Molecular Bases of Inherited Disease","author":"Goldstein JL","year":"2001","unstructured":"Goldstein JL, Hobbs HH, Brown MS. Part 12: Lipids: chapter 120: Familial Hypercholesterolemia. , Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B, Childs B, eds. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill Medical; 2001:2863\u20132913."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001236"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15467-6"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(02)00003-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.301430"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv157"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-2107C"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.145151"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.10.042"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2015.07.011"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2013.06.010"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.181946"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-2712(18)30645-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X148472"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.12.1344"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.3.331"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.8892"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn422"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a2423"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.116.025158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T02:40:31Z","timestamp":1715568031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.116.025158"}},"subtitle":["The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label)"],"short-title":[],"issued":{"date-parts":[[2017,7,25]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,7,25]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.116.025158"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.116.025158","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,25]]},"assertion":[{"value":"2016-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}