title: Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease.
abstract: OBJECTIVE
  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.
authors: Cardiology, Swiss Cardiovascular Center Bern, University Hospital Bern, Switzerland.
authors: Kerstin
authors: K
authors: Wustmann
authors: Marco
authors: M
authors: Klaey
authors: Annika
authors: A
authors: Burow
authors: Sidney G
authors: SG
authors: Shaw
authors: Otto M
authors: OM
authors: Hess
authors: Yves
authors: Y
authors: Allemann
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001916:Brachial Artery / Q000502:physiology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D004311:Double-Blind Method; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D023381:Endpoint Determination; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011743:Pyrimidines / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014803:Vitamin B Complex / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D014815:Vitamins / Q000097:blood / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D013449:Sulfonamides; D014815:Vitamins; D006710:Homocysteine; D014803:Vitamin B Complex; D000068718:Rosuvastatin Calcium