Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease

Cardiovasc Ther. 2012 Oct;30(5):277-86. doi: 10.1111/j.1755-5922.2011.00272.x. Epub 2011 Jul 31.

Abstract

Aim: Endothelial dysfunction is a marker for development and progression of atherosclerosis. Statin therapy improves endothelial function in cardiovascular patients by reducing LDL-cholesterol and by pleiotropic effects. B-group vitamin supplementation restores endothelial function mainly by reducing homocysteine-induced oxidative stress. Thus, we evaluated the effect of rosuvastatin, B-group vitamins and their combination on endothelial function in high-risk cardiovascular patients.

Methods: Thirty-six patients with cardiovascular disease were randomly, double-blinded assigned to either rosuvastatin 10 mg (group R, n = 18) or vitamin supplementation consisting of folic acid 1 mg, vitamin B12 0.4 mg, and B6 10 mg (group V, n = 18) for 6 weeks. After 6 weeks all patients received rosuvastatin and vitamin supplementation in combination for additional 6 weeks. Endothelial function was assessed by flow-mediated vasodilation (FMD) at baseline and after 6- and 12-week treatment.

Results: At baseline, FMD, plasma lipids, vitamins, and homocysteine were comparable between both groups. After 6 weeks, FMD improved in both groups (from 4.4 ± 1.6 to 6.9 ± 1.4% group R, P= 0.0004 and from 4.9 ± 1.8 to 6.4 ± 1.8% group V, P= 0.0002). This improvement in FMD was mainly associated with a decrease of plasma lipids in group R and a decrease of homocysteine in group V. After 12 weeks, the combined therapy with rosuvastatin and vitamins further improved FMD to the normal range in 26/33 patients compared to 5/36 at baseline (P < 0.0001).

Conclusions: In conclusion, both treatments, rosuvastatin and B-group vitamin supplementation, improved endothelial function in high-risk cardiovascular patients. The combination of both therapies had an additive effect on endothelial function suggesting different mechanisms of action.

Publication types

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

MeSH terms

  • Aged
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Brachial Artery / physiology
  • Cardiovascular Diseases / physiopathology*
  • Double-Blind Method
  • Endothelium / drug effects
  • Endothelium / physiology*
  • Endpoint Determination
  • Female
  • Fluorobenzenes / therapeutic use
  • Homocysteine / antagonists & inhibitors*
  • Homocysteine / blood
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lipids / blood
  • Male
  • Middle Aged
  • Patient Compliance
  • Pyrimidines / therapeutic use
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vitamin B Complex / adverse effects
  • Vitamin B Complex / blood
  • Vitamin B Complex / therapeutic use
  • Vitamins / blood
  • Vitamins / therapeutic use

Substances

  • Anticholesteremic Agents
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pyrimidines
  • Sulfonamides
  • Vitamins
  • Homocysteine
  • Vitamin B Complex
  • Rosuvastatin Calcium