title: Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.
abstract: OBJECTIVE
  Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution.
  
  
  METHODS
  A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24) or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. HDL subclasses were determined using polyacrylamide gel-tube electrophoresis. Multivariate regression models were used to determine the influence of treatment and covariates on changes in HDL subclass composition.
  
  
  RESULTS
  Baseline HDL subclasses consisted of 33±10% large, 48±6% intermediate and 19±8% small HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL-C and the ratio triglycerides/HDL-C, there was a significant increase in large HDL by about 3.9 percentage points (P<0.05) and a decrease in intermediate HDL by about 3.5 percentage points (P<0.01) in both simvastatin-containing treatment arms in comparison to ezetimibe. The parameters obtained after additional adjustment for the decrease in LDL-C indicated that about one third to one half of these effects could be explained by the extent of LDL-C-lowering.
  
  
  CONCLUSIONS
  In healthy men, treatment with simvastatin leads to favorable effects on HDL subclass composition, which was not be observed with ezetimibe. Part of these differential effects may be due to the stronger LDL-C-lowering effects of simvastatin.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00317993.
authors.affiliation: Department of Internal Medicine and Geriatrics, Bielefeld Evangelical Hospital (EvKB), Bielefeld, Germany.
authors.forename: Heiner K
authors.initials: HK
authors.lastname: Berthold
authors.affiliation: BioMedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Spenrath
authors.affiliation: BioMedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.affiliation: Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krone
authors.affiliation: Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gouni-Berthold
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005947:Glucose / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D054392:Adipokines; D001384:Azetidines; D015415:Biomarkers; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D019821:Simvastatin; D000069438:Ezetimibe; D005947:Glucose