title: Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease--a prospective randomized study of vitamin supplementation.
abstract: BACKGROUND
  Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers.
  
  
  METHODS
  A total of 93 patients with ischemic heart disease were investigated. Of these, 34 had plasma tHcy < or =8 micromol/L, while 59 had plasma tHcy > or = 15.0 micromol/L. The 59 patients were randomized to open therapy with folic acid, 5 mg, pyridoxine, 40 mg, and cyancobalamin, 1 mg once daily for 3 months (n = 29) or to no vitamin treatment (n = 30). Blood samples were obtained from both groups before randomization and 3 months later. A sample was also obtained from the remaining 34 patients.
  
  
  RESULTS
  Plasma Iso-P, serum amyloid A (S-AA), and plasma intercellular adhesion molecule-1 (ICAM-1) concentrations were higher in patients with high plasma tHcy levels than in patients with low to normal tHcy levels. Plasma levels of P-, L-, E-selectins, MDA, C-reactive protein (CRP), and orosomucoid did not differ between the groups. Vitamin therapy reduced plasma tHcy from 17.4 (15.3/20.1) to 9.2 (8.3/10.3) micromol/L (25th and 75th percentiles in parentheses) (p<0.0001). Plasma levels of Iso-P remained unchanged and, of all inflammatory markers, only the S-AA concentrations were slightly reduced by the vitamin treatment, from 5.3 (2.2/7.0) ng/L at baseline to 4.6 (2.1/6.9) ng/L (p<0.05) after 3 months of vitamin supplementation.
  
  
  CONCLUSIONS
  Patients with CAD and high plasma tHcy levels had elevated plasma levels of Iso-P. The increase remained unaffected by plasma tHcy-lowering therapy, suggesting that homocysteine per se does not cause increased lipid peroxidation. Levels of plasma ICAM-1 and S-AA were increased in patients with high plasma tHcy, suggesting an association between homocysteinemia and low-grade inflammation.
authors: Department of Cardiology, University Hospital Lund, Lund, Sweden. torfifja@landspitali.is
authors: Torfi
authors: T
authors: Jonasson
authors: Ann-Kristin
authors: AK
authors: Ohlin
authors: Anders
authors: A
authors: Gottsäter
authors: Björn
authors: B
authors: Hultberg
authors: Hans
authors: H
authors: Ohlin
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011736:Pyridoxine / Q000008:administration & dosage; D014805:Vitamin B 12 / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D011736:Pyridoxine; D014805:Vitamin B 12