The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients.
The proinflammatory mediator CD40 ligand plays an important role in atherogenesis. Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared the effects of these therapies either alone or in combination on plasma soluble CD40 ligand (sCD40L). This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20mg and placebo, simvastatin 20mg and losartan 100mg, or losartan 100mg and placebo daily during each 2 month treatment period. Simvastatin alone did not significantly reduce sCD40L levels relative to baseline measurements when the entire cohort was analyzed. However, simvastatin significantly reduced sCD40L levels from 5.10+/-0.34 to 3.07+/-0.43ng/ml (P=0.002) in a subgroup of 18 patients with high baseline sCD40L levels >2.95ng/ml. Combined therapy or losartan alone significantly decreased plasma sCD40L levels relative to baseline measurements by 14+/-7% (P=0.001) and 13+/-10% (P=0.001), respectively. These decreases were significantly greater than those observed with simvastatin alone (P=0.023 by ANOVA). Significant inverse correlations between baseline sCD40L levels and percent changes in sCD40L levels were observed (r=-0.456, P=0.001 after simvastatin alone; r=-0.476, P<0.001 after combined therapy; r=-0.451, P=0.002 after losartan alone). Losartan alone or combined therapy significantly reduced plasma sCD40L levels more than simvastatin alone in our subjects. Simvastatin, losartan and combined therapy significantly reduced sCD40L to the greatest extent in patients with high baseline sCD40L levels.
Han
Seung Hwan
SH
Vascular Medicine and Atherosclerosis Unit, Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, South Korea.
Koh
Kwang Kon
KK
Quon
Michael J
MJ
Lee
Yonghee
Y
Shin
Eak Kyun
EK
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000097:blood; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*; D012995:Solubility; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D023201:CD40 Ligand; D002097:C-Reactive Protein; D019821:Simvastatin; D019808:Losartan