Early statin therapy restores endothelial function in children with familial hypercholesterolemia.

Abstract

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.

• Authors: Saskia de Jongh, Marc R Lilien, Jos op't Roodt, Erik S G Stroes, Henk D Bakker, John J P Kastelein
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 40 Issue 12 Pg. 2117-21 (Dec 18 2002) ISSN: 0735-1097 [Print] United States
• PMID: 12505222 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• Simvastatin

Topics

• Adolescent
• Arteriosclerosis (prevention & control)
• Child
• Endothelium, Vascular (drug effects)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, therapeutic use)
• Hyperlipoproteinemia Type II (blood, drug therapy, physiopathology)
• Lipids (blood)
• Male
• Simvastatin (administration & dosage, therapeutic use)
• Treatment Outcome