Phenotype-dependent and -independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia

Atherosclerosis. 2003 Dec;171(2):245-53. doi: 10.1016/j.atherosclerosis.2003.08.025.

Abstract

This randomised, double-blind, placebo-controlled crossover study evaluated the effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B-containing lipoprotein subfractions. Subjects, recruited based on raised plasma triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided into normotriglyceridaemic (NTG, n = 13; TG < 2.0 mmol/l) and hypertriglyceridaemic (HTG, n = 16; TG > or = 2.0 mmol/l) groups. Similar reductions on rosuvastatin were observed for both groups in LDL-C (NTG -60%; HTG -56%), apoB (both -49%), intermediate-density lipoprotein (NTG -57%; HTG -54%) and LDL circulating mass (NTG -52%, HTG -58%) (all P < 0.001 versus placebo), i.e., these changes were phenotype independent. Phenotype dependency in response was observed in HTG relative to NTG in concentration of small dense LDL (LDL-III) (NTG -44%, P = NS; HTG -69%, P < 0.001), very-low-density lipoprotein1 (NTG -18%, P = NS; HTG 46%, P < 0.01), and remnant-like particle cholesterol (NTG -31%, P = NS; HTG -48%, P < 0.05). Rosuvastatin reduced cholesteryl ester transfer protein (CETP) by 33% in NTG and 37% in HTG (both P < 0.001); a reduction in cholesteryl ester transfer activity (-59%, P < 0.001) was observed in HTG only. Rosuvastatin therefore, in addition to lowering LDL and apoB-concentrations, largely corrected the TG and LDL abnormalities in subjects who had the propensity to develop the atherogenic lipoprotein phenotype.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Apolipoproteins / drug effects
  • Apolipoproteins / metabolism
  • Cholesterol / metabolism*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Fluorobenzenes / administration & dosage*
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / genetics
  • Hyperlipidemias / metabolism*
  • Lipoproteins / drug effects
  • Lipoproteins / metabolism*
  • Lipoproteins, LDL / drug effects*
  • Lipoproteins, LDL / metabolism
  • Lipoproteins, VLDL / drug effects*
  • Lipoproteins, VLDL / metabolism
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Phenotype
  • Probability
  • Pyrimidines / administration & dosage*
  • Reference Values
  • Rosuvastatin Calcium
  • Severity of Illness Index
  • Sulfonamides / administration & dosage*
  • Treatment Outcome
  • Triglycerides / metabolism*

Substances

  • Apolipoproteins
  • Fluorobenzenes
  • Lipoproteins
  • Lipoproteins, LDL
  • Lipoproteins, VLDL
  • Pyrimidines
  • Sulfonamides
  • Triglycerides
  • remnant-like particle cholesterol
  • Rosuvastatin Calcium
  • Cholesterol