Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy

J Am Coll Cardiol. 2003 Jan 15;41(2):275-9. doi: 10.1016/s0735-1097(02)02718-3.


Objectives: In the present study, we investigated the effects of statins on serum levels of soluble CD40 ligand (sCD40L) in patients with familial hypercholesterolemia (FH).

Background: Atherosclerotic disease seems to involve inflammatory and immunologic mechanisms, and sCD40L has recently been identified as one of the key players in the atherosclerotic process. HMG-Co A reductase inhibitors, statins, have been recognized as immunomodulators and reduce cardiovascular events and mortality, but the effects of statins on sCD40L has not been clarified.

Methods: In a randomized, double-blind, clinical trial, as part of the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) trial, 110 patients with FH were given atorvastatin 80 mg/daily (n = 57) or simvastatin 40 mg/daily (n = 53) for two years.

Results: Our main findings were: 1) at baseline patients with FH had significantly higher (approximately 27-fold) serum levels of sCD40L than healthy controls; 2) statin therapy markedly decreased serum levels of sCD40L (approximately 40% reduction); 3) this decrease in sCD40L was found during both "aggressive" (i.e., atorvastatin) and "conventional" (i.e., simvastatin) statin therapy and was not correlated with the degree of reduction in cholesterol levels.

Conclusions: Our findings may suggest enhanced CD40L-CD40 interaction in FH and that this inflammatory response may be downregulated by statins.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin
  • CD40 Ligand / blood*
  • Coronary Artery Disease / blood
  • Double-Blind Method
  • Down-Regulation / drug effects
  • Female
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / drug therapy*
  • Male
  • Middle Aged
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*
  • Treatment Outcome


  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • CD40 Ligand
  • Atorvastatin
  • Simvastatin