Published Online
on July 30, 2007

A more recent version of this article appeared on August 7, 2007

This Article Full Text (PDF) All Versions of this Article: 116/6/664    most recent CIRCULATIONAHA.106.671016v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rodenburg, J. Articles by Hutten, B. A. Search for Related Content PubMed PubMed Citation Articles by Rodenburg, J. Articles by Hutten, B. A. Pubmed/NCBI databases Genetics Home Reference Medline Plus Health Information Statins Related Collections Primary prevention Risk Factors Epidemiology Lipid and lipoprotein metabolism

Submitted on December 7, 2006
Accepted on May 25, 2007

Statin Treatment in Children With Familial Hypercholesterolemia. The Younger, the Better

Jessica Rodenburg MD, PhD, Maud N. Vissers PhD, Albert Wiegman MD, PhD, A. S. Paul van Trotsenburg MD, PhD, Anouk van der Graaf MD, Eric de Groot MD, PhD, Frits A. Wijburg MD, PhD, John J.P. Kastelein MD, PhD, and Barbara A. Hutten PhD^*

From the Departments of Vascular Medicine (J.R., M.N.V., A.v.d.G., E.d.G., J.J.P.K.), Paediatrics (A.W., A.S.P.v.T., F.A.W.), and Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

^* To whom correspondence should be addressed. E-mail: b.a.hutten{at}amc.uva.nl.

Background—We previously demonstrated in a randomized placebo-controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up.

Methods and Results—All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation.

Conclusions—These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence.

Key words: adolescents • atherosclerosis • child • hypercholesterolemia • statins

This article has been cited by other articles:

				A. S. Barth, T. Aiba, V. Halperin, D. DiSilvestre, K. Chakir, C. Colantuoni, R. S. Tunin, V. L. Dimaano, W. Yu, T. P. Abraham, et al. Cardiac Resynchronization Therapy Corrects Dyssynchrony-Induced Regional Gene Expression Changes on a Genomic Level Circ Cardiovasc Genet, August 1, 2009; 2(4): 371 - 378. [Abstract] [Full Text] [PDF]

				J H Baumer and J P H Shield Hypercholesterolaemia in children guidelines review Arch. Dis. Child. Ed. Pract., June 1, 2009; 94(3): 84 - 86. [Full Text] [PDF]

				J. Versmissen, D. M Oosterveer, M. Yazdanpanah, J. C Defesche, D. C G Basart, A. H Liem, J. Heeringa, J. C Witteman, P. J Lansberg, J. J P Kastelein, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study BMJ, November 11, 2008; 337(nov11_1): a2423 - a2423. [Abstract] [Full Text] [PDF]

				P. O. Kwiterovich Jr. Recognition and Management of Dyslipidemia in Children and Adolescents J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4200 - 4209. [Abstract] [Full Text] [PDF]

				A. van der Graaf, C. Cuffie-Jackson, M. N. Vissers, M. D. Trip, C. Gagne, G. Shi, E. Veltri, H. J. Avis, and J. J.P. Kastelein Efficacy and Safety of Coadministration of Ezetimibe and Simvastatin in Adolescents With Heterozygous Familial Hypercholesterolemia J. Am. Coll. Cardiol., October 21, 2008; 52(17): 1421 - 1429. [Abstract] [Full Text] [PDF]

				D. Steinberg, C. K. Glass, and J. L. Witztum Evidence Mandating Earlier and More Aggressive Treatment of Hypercholesterolemia Circulation, August 5, 2008; 118(6): 672 - 677. [Full Text] [PDF]

				I. Tabas, K. J. Williams, and J. Boren Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis: Update and Therapeutic Implications Circulation, October 16, 2007; 116(16): 1832 - 1844. [Abstract] [Full Text] [PDF]

				E. A. Stein Statins and Children: Whom Do We Treat and When? Circulation, August 7, 2007; 116(6): 594 - 595. [Full Text] [PDF]