title: The effect of simvastatin-ezetimibe combination therapy on adipose tissue hormones and systemic inflammation in patients with isolated hypercholesterolemia.
abstract: BACKGROUND
  Pleiotropic effects of ezetimibe have only been investigated in a few studies. The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low-grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia.
  
  
  METHODS
  The study included 69 patients with elevated cholesterol levels, who were allocated to one of the three groups treated for 12 weeks, respectively, with simvastatin (40 mg daily), simvastatin (40 mg daily) plus ezetimibe (10 mg daily), or placebo. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-α (TNF-α), free fatty acids (FFA), and high-sensitive C-reactive protein (hsCRP) were determined on the allocation day and after 12 weeks of therapy.
  
  
  RESULTS
  Apart from improving lipid profile, simvastatin administered alone or in combination with ezetimibe, decreased plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-α, as well as increased plasma levels of adiponectin. The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins, hsCRP, FFA, and the investigated adipokines. The effect of the combination therapy, but not of simvastatin, on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects.
  
  
  CONCLUSIONS
  The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe.
authors.affiliation: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Krysiak
authors.forename: Witold
authors.initials: W
authors.lastname: Zmuda
authors.forename: Bogusław
authors.initials: B
authors.lastname: Okopien
mesh_terms: D054392:Adipokines / Q000097:blood*; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003131:Combined Modality Therapy; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D040242:Risk Reduction Behavior; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D018836:Inflammation Mediators; D008055:Lipids; D019821:Simvastatin
keywords: Adiponectin; Ezetimibe; Hypercholesterolemia; Leptin; Statins; Tumor necrosis factor-α (TNF-α); Visfatin