Long-term beneficial effects of statins on vascular manifestations in patients with systemic sclerosis.
We conducted a 24-month, open-label trial to evaluate the long-term effects of statins on vascular symptoms in patients with systemic sclerosis (SSc). Ten patients received 10 mg/day atorvastatin, but two dropped out to treat other organ involvement. Raynaud's phenomenon, global measures of health, and psychological scales were assessed in addition to circulating angiogenic factors and endothelial activation/injury markers in eight patients at 0 (pretreatment), 1, 3, 12, and 24 months of treatment. Circulating endothelial progenitor cells (EPCs) were serially quantified by cell sorting and three-color flow cytometry. There were no adverse events. Raynaud's phenomenon improved during atorvastatin treatment, with significant reductions in the Raynaud's Condition Score (P = 0.01) and the patient assessment by visual analog scale (P = 0.0003). SSc-associated upregulation of angiogenic factors and vascular endothelial activation/injury markers were reduced (P < 0.01 for all comparisons). Improvement in these parameters was best at 12 and 24 months of treatment. The EPC number was increased at 1 month of treatment (P < 0.01), but soon dropped below baseline. This pilot study suggests that statins may be beneficial in treating vascular manifestations of SSc, through their pleiotropic effects. However, this treatment did not correct the defect in EPC recruitment.
Kuwana
Masataka
M
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. kuwanam@sc.itc.keio.ac.jp
Okazaki
Yuka
Y
Kaburaki
Junichi
J
D000368:Aged; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D002452:Cell Count; D002469:Cell Separation; D018450:Disease Progression; D019040:E-Selectin / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006304:Health Status; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D047468:Immunoprecipitation; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D011928:Raynaud Disease / Q000188:drug therapy* / Q000209:etiology; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy*; D012720:Severity of Illness Index; D013234:Stem Cells / Q000166:cytology; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000924:Anticholesteremic Agents; D019040:E-Selectin; D006538:Heptanoic Acids; D011758:Pyrroles; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000069059:Atorvastatin