Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease

Eur Heart J. 2008 Jul;29(14):1753-60. doi: 10.1093/eurheartj/ehn166. Epub 2008 Apr 25.

Abstract

Aims: The importance of pleiotropic effects of statins on endothelial function and inflammatory markers was investigated in patients with dysglycaemia and coronary artery disease (CAD).

Methods and results: Thirty-nine patients were randomized to simvastatin 80 mg daily (S80; n = 20) or ezetimibe 10 mg and simvastatin 10 mg daily (E10/S10; n = 19) for 6 weeks, aiming at similar cholesterol reduction. Endothelial function, evaluated by brachial artery flow-mediated vasodilatation (FMD) and the effect of endothelin receptor blockade, serum lipids, and inflammatory markers were evaluated at baseline and follow-up. At follow-up, low-density lipoprotein cholesterol decreased from 3.1 (2.8-3.4) (median and quartiles) to 1.5 mmol/L (1.4-1.7) and from 3.0 (2.5-3.4) to 1.3 mmol/L (1.1-1.8), in the S80 and E10/S10 groups, respectively. In the entire study group, FMD increased from 4.3% (3.4-6.1) at baseline to 5.5% (3.4-6.6) at follow-up, while C-reactive protein decreased from 3.1 (1.7-7.6) to 2.3 mg/L (0.9-6.5). The changes in FMD and C-reactive protein from baseline to follow-up were not significantly different between patients on S80 and E10/S10 groups. Endothelin blockade enhanced endothelium-dependent vasodilatation both at baseline and follow-up.

Conclusion: Lipid lowering is more important than pleiotropic effects of statins for improvement in endothelial function and inflammatory markers in patients with dysglycaemia and CAD.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Azetidines / pharmacology
  • Azetidines / therapeutic use
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • Cholesterol / blood*
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Ezetimibe
  • Female
  • Forearm / blood supply
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperglycemia / blood
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / physiopathology
  • Inflammation Mediators / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Plethysmography / methods
  • Regional Blood Flow / drug effects
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use
  • Vasodilation / drug effects

Substances

  • Azetidines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Inflammation Mediators
  • Lipids
  • Cholesterol
  • Simvastatin
  • Ezetimibe