Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy.
OBJECTIVE
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.
Semb
Anne G
AG
Cardiologic Department, Aker Hospital, Oslo, Norway.
van Wissen
Sanne
S
Ueland
Thor
T
Smilde
Tineke
T
Waehre
Torgun
T
Tripp
Mieke D
MD
Frøland
Stig S
SS
Kastelein
John J P
JJ
Gullestad
Lars
L
Pedersen
Terje R
TR
Aukrust
Pål
P
Stalenhoef
Anton F H
AF
D000069059:Atorvastatin; D023201:CD40 Ligand / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D023201:CD40 Ligand; D000069059:Atorvastatin; D019821:Simvastatin