HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe.

Abstract
In addition to their expected effects on lipid profile, lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation. Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols. Although it is known that an additional reduction of low-density lipoprotein cholesterol (LDL-C) levels can be induced by the combination of ezetimibe with statins, it is not known if this can enhance some pleiotropic effects, which may be useful in slowing the atherosclerotic process. This study assessed the effects of simvastatin and ezetimibe, in monotherapy or in combination, on markers of endothelial function and insulin sensitivity. Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were randomly allocated to 2 groups receiving either ezetimibe (10 mg/d) or simvastatin (20 mg/d) for 12 weeks, after which the drugs were combined for both groups for an additional 12-week period. Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy. Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated. As expected, both groups receiving drugs in isolation significantly reduced total cholesterol, LDL-C, apolipoprotein B, and triglyceride levels; and additional reductions were found after the combination period (P < .05). After 12 weeks of monotherapy, plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group. No change in homeostasis model assessment of insulin resistance index, area under the curve of insulin, and adiponectin levels was observed after either the monotherapies or the combined therapy. However, simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes. Our findings support claims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia. Alternatively, a deleterious effect of ezetimibe on the endothelial function is suggested, considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels. Simvastatin and ezetimibe, in isolation or in combination, do not interfere with insulin sensitivity.
AuthorsAna Lucia de Almeida Kater, Marcelo Costa Batista, Sandra Roberta Gouvea Ferreira
JournalMetabolism: clinical and experimental (Metabolism) Vol. 59 Issue 6 Pg. 921-6 (Jun 2010) ISSN: 1532-8600 [Electronic] United States
PMID20199786 (Publication Type: Journal Article, Randomized Controlled Trial)
CopyrightCopyright 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Anticholesteremic Agents
  • Azetidines
  • Biomarkers
  • Blood Glucose
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Simvastatin
  • Ezetimibe
Topics
  • Adolescent
  • Adult
  • Aged
  • Anthropometry
  • Anticholesteremic Agents (therapeutic use)
  • Azetidines (therapeutic use)
  • Biomarkers
  • Blood Coagulation (drug effects)
  • Blood Glucose (metabolism)
  • Body Mass Index
  • Drug Therapy, Combination
  • Endothelium, Vascular (drug effects, physiology)
  • Ezetimibe
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
  • Insulin Resistance (physiology)
  • Lipids (blood)
  • Male
  • Middle Aged
  • Prediabetic State (blood, drug therapy, physiopathology)
  • Simvastatin (therapeutic use)
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: