title: Impact of pitavastatin on high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome: the PREMIUM Study.
abstract: BACKGROUND
  Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted.
  
  
  OBJECTIVE
  To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial.
  
  
  METHODS
  This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks.
  
  
  RESULTS
  In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009).
  
  
  CONCLUSIONS
  Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.
authors.affiliation: Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan. matt@dpc.aichi-gakuin.ac.jp
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Takemi
authors.initials: T
authors.lastname: Arakawa
authors.forename: Masahide
authors.initials: M
authors.lastname: Nakao
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Marui
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Amano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichimiya
authors.forename: Taiki
authors.initials: T
authors.lastname: Ohashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Imai
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakai
authors.forename: Satoru
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishii
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D052242:Adiponectin / Q000097:blood*; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control; D002097:C-Reactive Protein / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D024821:Metabolic Syndrome / Q000150:complications*; D008970:Molecular Weight; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D052242:Adiponectin; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D002097:C-Reactive Protein; C108475:pitavastatin