title: Effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma high-sensitivity C-reactive protein in hypercholesterolemic patients with and without type 2 diabetes mellitus: A 12-week, open-label, pilot study.
abstract: BACKGROUND
  Oxidative stress and inflammation of the arterial wall are now recognized as important factors in the progression of atherosclerosis. C-reactive protein (CRP) has been defined as a sensitive but not specific marker of inflammation. Statin therapy has been reported to decrease plasma high-sensitivity CRP (hs-CRP) concentration in hypercholesterolemic patients.
  
  
  OBJECTIVE
  The aim of this study was to examine the effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP in hypercholesterolemic patients with and without type 2 diabetes mellitus.
  
  
  METHODS
  Patients with hypercholesterolemia with and without type 2 diabetes mellitus were enrolled in this pilot study after written informed consent was given. At baseline and after 12 weeks of open-label treatment with rosuvastatin 2.5 mg/d, concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP were measured. Urine 8-iso-prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were also measured to asess whole-body oxidative stress. Plasma free-radical generation was estimated using a total reactive oxygen species (TROS) assay system. Adverse effects were assessed at each study visit (4-week intervals) through patient interviews and laboratory testing.
  
  
  RESULTS
  Thirty-five patients were enrolled with 1 dropping out prior to study completion; therefore, 34 patients (19 women, 15 men; mean [SE] age, 55.4 [13.6] years; range, 30-78 years) completed the study. Compared with baseline, significant decreases were found in serum concentrations of total cholesterol (TC) (252.3 [39.3] vs 187.8 [30.1] mg/dL; P < 0.001; Δ = 24.5%), LDL-C (162.0 [44.3] vs 98.5 [31.9] mg/dL; P < 0.001; Δ = 38.7%), and triglycerides (TG) (157.2 [93.6] vs 124.4 [69.9] mg/dL; P < 0.05; Δ = 11.7%) after 12 weeks of treatment with rosuvastatin. Serum HDL-C concentration did not change significantly from baseline (59.7 [20.5] vs 63.7 [19.3] mg/dL; Δ = 9.4%). The plasma LDL-C/HDL-C ratio decreased significantly after rosuvastatin treatment (3.03 [1.33] vs 1.72 [0.83]; P < 0.001; Δ = 43.2%). Compared with baseline, significant decreases were observed in urine concentrations of the oxidative stress markers after 12 weeks of rosuvastatin treatment: 8-iso-PGF2α (342.8 [154.3] vs 300.6 [101.2] pg/mg; P < 0.05) and 8-OHdG (11.1 [4.53] vs 8.1 [2.7] ng/mg; P < 0.01). TROS decreased significantly (182.3 [29.0] vs 157.6 [17.3] U; P < 0.001), and plasma hs-CRP concentration also decreased significantly (0.107 [0.100] vs 0.054 [0.033] mg/dL; P < 0.05). When the patients' results were assessed according to the presence or absence of type 2 diabetes mellitus, urine 8-iso-PGF2α concentration was significantly decreased from baseline only in the nondiabetic group. No adverse events were reported or observed during the course of the study.
  
  
  CONCLUSIONS
  Rosuvastatin treatment was associated with significant reductions in plasma concentrations of TC, LDL-C, and TG, urine and plasma oxidative stress markers, and plasma hs-CRP in these hypercholesterolemic patients.
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Yoshino
authors.affiliation: Clinical Laboratory, Ohmori Hospital Medical Center, Toho University, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Saburo
authors.initials: S
authors.lastname: Nakano
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Clinical Laboratory, Ohmori Hospital Medical Center, Toho University, Tokyo, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Murakami
authors.affiliation: Department of Laboratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Morita
keywords: hs-CRP; hypercholesterolemia; oxidative stress; rosuvastatin; type 2 diabetes