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Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label).
Braamskamp, Marjet J A M; Langslet, Gisle; McCrindle, Brian W; Cassiman, David; Francis, Gordon A; Gagne, Claude; Gaudet, Daniel; Morrison, Katherine M; Wiegman, Albert; Turner, Traci; Miller, Elinor; Kusters, D Meeike; Raichlen, Joel S; Martin, Paul D; Stein, Evan A; Kastelein, John J P; Hutten, Barbara A.
Afiliação
  • Braamskamp MJAM; 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
  • Langslet G; 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
  • McCrindle BW; 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
  • Cassiman D; 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
  • Francis GA; 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
  • Gagne C; 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
  • Gaudet D; 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
  • Morrison KM; 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
  • Wiegman A; 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
  • Turner T; 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
  • Miller E; 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
  • Kusters DM; 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
  • Raichlen JS; 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
  • Martin PD; 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
  • Stein EA; 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
  • Kastelein JJP; 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
  • Hutten BA; 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
Circulation ; 136(4): 359-366, 2017 Jul 25.
Article em En | MEDLINE | ID: mdl-28592434
ABSTRACT

BACKGROUND:

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.

METHODS:

Children with HeFH (age, 6-<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-<10 years) or 20 mg (age, 10-<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. P values were adjusted for age, sex, carotid artery site, and family relations.

RESULTS:

At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively; P=0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030-0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095-0.0192) in unaffected siblings (P=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±0.043 and 0.402±0.042 mm, respectively; P=0.2).

CONCLUSIONS:

In children with HeFH who were ≥6 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. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT01078675.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espessura Intima-Media Carotídea / Rosuvastatina Cálcica / Heterozigoto / Hiperlipoproteinemia Tipo II / Anticolesterolemiantes Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espessura Intima-Media Carotídea / Rosuvastatina Cálcica / Heterozigoto / Hiperlipoproteinemia Tipo II / Anticolesterolemiantes Idioma: En Ano de publicação: 2017 Tipo de documento: Article