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J Am Coll Cardiol, 2002; 40:2117-2121 © 2002 by the American College of Cardiology Foundation |
,
,*
,
* Emma Children’s Hospital, AMC, Amsterdam, Netherlands
Department of Vascular Medicine, Academic Medical Center Amsterdam, Netherlands
Wilhelmina Children’s Hospital, Utrecht, Netherlands
Manuscript received March 18, 2002; revised manuscript received June 6, 2002, accepted July 18, 2002.
* Reprint requests and correspondence: Dr. Saskia de Jongh, Department of Vascular Medicine, Academic Medical Center, G1-146, Meibergdreef 9, PO Box 22660, 1100 DD, Amsterdam, Netherlands.
s.dejongh{at}amc.uva.nl
OBJECTIVES: This study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH).
BACKGROUND: Endothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD.
METHODS: The study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment.
RESULTS: At baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% ± 4.3% vs. 1.2% ± 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% ± 6.8% vs. 15.5% ± 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (–2.16 ± 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (–2.13 ± 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = –0.31, p < 0.05) and LDL-C (r = –0.31, p < 0.05).
CONCLUSIONS: Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible.
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