Lipid-lowering therapy does not affect the postprandial drop in high density lipoprotein-cholesterol (HDL-c) plasma levels in obese men with metabolic syndrome: a randomized double blind crossover trial

Clin Endocrinol (Oxf). 2008 Dec;69(6):870-7. doi: 10.1111/j.1365-2265.2008.03250.x. Epub 2008 Apr 3.

Abstract

Introduction: The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein-cholesterol (HDL-c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment.

Methods: Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL-c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL-c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085.

Results: Plasma HDL-c levels remained stable during continuous fasting following an overnight fast. Pre-fat load HDL-c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1.15 +/- 0.04, 1.16 +/- 0.05 and 1.11 +/- 0.04 mmol/l. Fat load induced a 11% drop in HDL-c plasma levels; 1.02 +/- 0.05 mmol/l (P < 0.001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9.73 +/- 0.70 to 12.20 +/- 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment.

Discussion: HDL-c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra-abdominal fat. Decreased postprandial HDL-c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL-c levels.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Azetidines / therapeutic use*
  • Cholesterol Ester Transfer Proteins / blood
  • Cholesterol, HDL / blood*
  • Cross-Over Studies
  • Dietary Fats
  • Double-Blind Method
  • Drug Combinations
  • Ezetimibe
  • Fasting
  • Humans
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / drug therapy*
  • Middle Aged
  • Obesity / drug therapy
  • Postprandial Period
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*

Substances

  • Azetidines
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Dietary Fats
  • Drug Combinations
  • Simvastatin
  • Ezetimibe

Associated data

  • ClinicalTrials.gov/NCT00189085