Early statin therapy restores endothelial function in children with familial hypercholesterolemia

J Am Coll Cardiol. 2002 Dec 18;40(12):2117-21. doi: 10.1016/s0735-1097(02)02593-7.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

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


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Simvastatin