title: Effects of simvastatin and ezetimibe on interleukin-6 and high-sensitivity C-reactive protein.
abstract: OBJECTIVE
  Statins decrease cardiovascular events mainly by lowering cholesterol but anti-inflammatory effects also play a role. The effects of the cholesterol absorption inhibitor ezetimibe on markers of inflammation remain unclear. We performed an exploratory post-hoc analysis whether these drugs influence the pro-inflammatory markers interleukin-6 and high-sensitivity C-reactive protein in subjects with very-low cardiovascular risk.
  
  
  METHODS
  Single center, randomized, parallel 3-group study in 72 healthy men without apparent cardiovascular disease (age 32 ± 9 years, BMI 25.7 ± 3.2 kg/m(2)). Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination.
  
  
  RESULTS
  Baseline IL-6 and hsCRP concentrations in the total cohort were 0.72 ± 0.57 ng/l and 0.40 ± 0.65 mg/l, respectively, with no differences between the 3 groups. Median changes (interquartile range) in IL-6 and hsCRP concentrations were -22% (-43 to 0%) and -30% (-44 to +19%) after simvastatin, -5% (-36 to +30%) and +9% (-22 to +107%) after ezetimibe, and +15% (-15 to +86%) and +1 (-30 to +49%) after the combination. Using a generalized linear model, the multivariable adjusted overall P-values for these changes were 0.008 (IL-6) and 0.1 (hsCRP).
  
  
  CONCLUSIONS
  Simvastatin decreases the pro-inflammatory markers IL-6 and almost significantly hsCRP while ezetimibe monotherapy or the combination with simvastatin has no effect.
authors.affiliation: Charité University Medicine Berlin, Evangelical Geriatrics Center Berlin (EGZB), Berlin, Germany. heiner.berthold@charite.de
authors.forename: Heiner K
authors.initials: HK
authors.lastname: Berthold
authors.forename: Kaspar
authors.initials: K
authors.lastname: Berneis
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krone
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gouni-Berthold
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D000069438:Ezetimibe; D000069499:Ezetimibe, Simvastatin Drug Combination; D005858:Germany; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D002097:C-Reactive Protein; D019821:Simvastatin; D000069438:Ezetimibe