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Circulation. 2017 Jul 25;136(4):359-366. doi: 10.1161/CIRCULATIONAHA.116.025158. Epub 2017 Jun 7.

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).

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1
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 Center, University Hospitals Leuven, Belgium (D.C.); Healthy Heart Program Prevention Clinic, St. Paul's Hospital, Vancouver, British Columbia, Canada (G.A.F.); Department of Medicine, University of British Columbia, Vancouver, Canada (G.A.F.); Clinique des Maladies Lipidiques de Québec Inc, Québec, QC, Canada (C.G.); Department of Medicine, Université de Montréal, Montréal, Québec, Canada (D.G.); Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada (K.M.M.); Metabolic & Atherosclerosis Research Center, Cincinnati, OH (T.T., E.A.S.); AstraZeneca Pharmaceuticals LP, Wilmington, DE (E.M., J.S.R.); and AstraZeneca, Macclesfield, Cheshire, United Kingdom (P.D.M.).
2
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 Center, University Hospitals Leuven, Belgium (D.C.); Healthy Heart Program Prevention Clinic, St. Paul's Hospital, Vancouver, British Columbia, Canada (G.A.F.); Department of Medicine, University of British Columbia, Vancouver, Canada (G.A.F.); Clinique des Maladies Lipidiques de Québec Inc, Québec, QC, Canada (C.G.); Department of Medicine, Université de Montréal, Montréal, Québec, Canada (D.G.); Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada (K.M.M.); Metabolic & Atherosclerosis Research Center, Cincinnati, OH (T.T., E.A.S.); AstraZeneca Pharmaceuticals LP, Wilmington, DE (E.M., J.S.R.); and AstraZeneca, Macclesfield, Cheshire, United Kingdom (P.D.M.). b.a.hutten@amc.uva.nl.

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.

KEYWORDS:

carotid intima-media thickness; child; cholesterol, LDL; hypercholesterolemia, familial; rosuvastatin calcium

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