CLINICAL STUDY: MANAGEMENT OF HYPERCHOLESTEROLEMIA
Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy
Anne G. Semb, MD, PhD*,
Sanne van Wissen, MD ,
Thor Ueland, BS ,
Tineke Smilde, MD, PhD,
Torgun Waehre, MD,
Mieke D. Tripp, MD, PhD ,
Stig S. Frøland, MD, PhD||,
John J. P. Kastelein, MD, PhD,
Lars Gullestad, MD, PhD¶,
Terje R. Pedersen, MD, PhD*,
P.ål Aukrust, MD, PhD||,* and
Anton F. H. Stalenhoef, MD, PhD
* Cardiologic Department, Aker Hospital, Oslo, Norway
Research Institute for Internal Medicine, Oslo, Norway
|| Section of Clinical Immunology and Infectious Diseases, Rikshospitalet, Oslo, Norway
¶ Medical Department, Baerum Hospital, Baerum, Norway
Academic Medical Center, Amsterdam, The Netherlands
Department of Medicine, University Medical Center, Nijmegen, The Netherlands
Manuscript received April 29, 2002;
revised manuscript received September 20, 2002,
accepted October 4, 2002.
* Reprint requests and correspondence: Dr. Pål Aukrust, Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet, N-0027 Oslo, Norway.
pal.aukrust{at}rikshospitalet.no
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.
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Abbreviations and Acronyms
| | CVD | | cardiovascular disease | | EIA | | enzyme immunoassay | | FH | | familial hypercholesterolemia | | hsCRP | | high-sensitivity C-reactive protein | | IMT | | intima media thickness | | LDL | | low-density lipoprotein | | LDL-C | | LDL cholesterol | | sCD40L | | soluble CD40 ligand |
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