title: Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial.
abstract: BACKGROUND
  Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients.
  
  
  METHODS
  The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50  μmol/l), treated with B-vitamins (500  μg vitamin B12 and 400  μg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima-media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured.
  
  
  RESULTS
  Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6  μmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed.
  
  
  CONCLUSIONS
  Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes.
authors.affiliation: aErasmus MC, Department of Internal Medicine, Rotterdam bVU University Medical Center, EMGO Institute for Health and Care Research, Department of Epidemiology and Biostatistics, Amsterdam cWageningen University, Division of Human Nutrition, Wageningen dVU University Medical Center, Department of Clinical Chemistry eVU University Medical Center, Department of Internal Medicine, Amsterdam fNetherlands Consortium for Healthy Ageing, Rotterdam, Leiden gVU University Medical Center, Institute for Cardiovascular Research ICaR-VU hAcademic Medical Center, Department of Internal Medicine, Section of Geriatrics, Amsterdam, the Netherlands.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Dijk
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.forename: Karin M A
authors.initials: KM
authors.lastname: Swart
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.forename: Annelies C
authors.initials: AC
authors.lastname: Ham
authors.forename: Elske M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.forename: Nikita L
authors.initials: NL
authors.lastname: van der Zwaluw
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Edith J
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Johanna Marianna
authors.initials: JM
authors.lastname: Geleijnse
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.forename: Renate T
authors.initials: RT
authors.lastname: de Jongh
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.forename: Francesco U S
authors.initials: FU
authors.lastname: Mattace Raso
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000401:mortality / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000401:mortality / Q000503:physiopathology*; D059168:Carotid Intima-Media Thickness; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D063177:Pulse Wave Analysis; D012307:Risk Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology; D014805:Vitamin B 12 / Q000008:administration & dosage*
chemical_list: D005492:Folic Acid; D014805:Vitamin B 12