title: A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction.
abstract: Sickle cell disease (SCD) is characterized by progressive vascular injury and its pathophysiology is strikingly similar to that of atherosclerosis. Statins decrease inflammation and improve endothelial function in cardiovascular disease, but their effect in SCD is not known. In this pilot study, we examined the safety and effect of short-term simvastatin on biomarkers of vascular dysfunction in SCD. We treated 26 SCD patients with simvastatin, 20 or 40 mg/d, for 21 d. Plasma nitric oxide metabolites (NOx), C-reactive protein (CRP), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), tissue factor (TF) and vascular endothelial growth factor (VEGF) were analyzed and responses to simvastatin were compared between the two treatment groups. Simvastatin increased NOx levels by 23% in the low-dose (P =0·01) and 106% in the moderate-dose (P =0·01) groups, and by 52% overall (P=0·0008). CRP decreased similarly in both dose groups and by 68% overall (P =0·02). Levels of IL-6 decreased by 50% (P=0·04) and 71% (P<0·05) in the low- and moderate-dose groups, respectively. Simvastatin had no effect on VEGF, VCAM1 or TF. Simvastatin was well-tolerated and safe. Our preliminary findings showing a dose-related effect of simvastatin on levels of NOx, CRP and IL-6 suggest a potential therapeutic role for simvastatin in SCD.
authors.affiliation: Department of Haematology/Oncology, Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609, USA. choppe@mail.cho.org
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hoppe
authors.forename: Frans
authors.initials: F
authors.lastname: Kuypers
authors.forename: Sandra
authors.initials: S
authors.lastname: Larkin
authors.forename: Ward
authors.initials: W
authors.lastname: Hagar
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Lori
authors.initials: L
authors.lastname: Styles
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D010865:Pilot Projects; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D015850:Interleukin-6; D008055:Lipids; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin