title: Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease.
abstract: OBJECTIVE
  A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine-lowering B-vitamin therapy, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis.
  
  
  METHODS
  Single centre, prospective double-blind clinical interventional study, randomised in a 2 x 2 factorial design.
  
  
  METHODS
  Ninety patients (21 female) with suspected coronary artery disease (CAD), aged 38-80 years, were blindly randomised into one of four groups of daily oral treatment with (A) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), (B) folic acid/vitamin B12, (C) vitamin B6 alone or (D) placebo. Blood samples were collected before and after 6 months of treatment.
  
  
  RESULTS
  Before intervention, median levels of the analytes were: tHcy 11.0 micromol L(-1), neopterin 8.1 nmol L(-1), soluble CD40 ligand (sCD40L) 3.9 ng mL(-1), interleukin (IL)-6 1.9 pg mL(-1), C-reactive protein (CRP) 1.9 mg L(-1) and low-density lipoprotein (LDL) cholesterol 3.3 mmol L(-1). tHcy was significantly associated with neopterin (r = 0.49, P < 0.001) and with IL-6 (r = 0.29, P = 0.01), but not with CRP or sCD40L. Neither treatment with folic acid/B12 nor with B6 induced significant changes in any of these inflammatory biomarkers (P >or= 0.14). In patients receiving folic acid/B12 (groups A and B), tHcy was reduced with 33% (P < 0.001).
  
  
  CONCLUSIONS
  In patients with stable CAD, homocysteine-lowering therapy with B-vitamins does not affect levels of inflammatory markers associated with atherogenesis. Failure to reverse inflammatory processes, may partly explain the negative results in clinical secondary B-vitamin intervention trials.
authors.affiliation: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. oyvind.bleie@helse-bergen.no
authors.forename: Ø
authors.initials: Ø
authors.lastname: Bleie
authors.forename: A G
authors.initials: AG
authors.lastname: Semb
authors.forename: H
authors.initials: H
authors.lastname: Grundt
authors.forename: J E
authors.initials: JE
authors.lastname: Nordrehaug
authors.forename: S E
authors.initials: SE
authors.lastname: Vollset
authors.forename: P M
authors.initials: PM
authors.lastname: Ueland
authors.forename: D W T
authors.initials: DW
authors.lastname: Nilsen
authors.forename: A M
authors.initials: AM
authors.lastname: Bakken
authors.forename: H
authors.initials: H
authors.lastname: Refsum
authors.forename: O K
authors.initials: OK
authors.lastname: Nygård
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D023201:CD40 Ligand / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D011446:Prospective Studies; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000097:blood; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000097:blood
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D015850:Interleukin-6; D006710:Homocysteine; D014803:Vitamin B Complex; D023201:CD40 Ligand; D019798:Neopterin; D025101:Vitamin B 6; D002097:C-Reactive Protein; D005492:Folic Acid; D014805:Vitamin B 12