The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis

BMC Cardiovasc Disord. 2008 Sep 20:8:24. doi: 10.1186/1471-2261-8-24.

Abstract

Background: Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.

Methods: We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.

Results: After a mean treatment period of 3.9 +/- 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 micromol/L, 95% CI 7.5 to 8.4 versus 11.8 micromol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 +/- 0.17 mm vitamins versus 0.83 +/- 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.

Conclusion: Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.

Publication types

  • Meta-Analysis
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Carotid Arteries / drug effects*
  • Carotid Arteries / pathology
  • Carotid Arteries / physiopathology
  • Dietary Supplements*
  • Double-Blind Method
  • Down-Regulation
  • Drug Combinations
  • Female
  • Folic Acid / therapeutic use
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Regional Blood Flow
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / physiopathology
  • Time Factors
  • Treatment Outcome
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology
  • Tunica Intima / physiopathology
  • Tunica Media / drug effects*
  • Tunica Media / pathology
  • Tunica Media / physiopathology
  • Vasodilation / drug effects*
  • Vitamin B 12 / therapeutic use
  • Vitamin B 6 / therapeutic use
  • Vitamin B Complex / therapeutic use*

Substances

  • Drug Combinations
  • Homocysteine
  • Vitamin B Complex
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12