Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial.

Abstract

BACKGROUND AND PURPOSE:

Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability.

METHODS:

We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability.

RESULTS:

At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1 [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy).

CONCLUSIONS:

Lowering tHcy by 3.7 micromol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.

• Authors: P Dusitanond, J W Eikelboom, G J Hankey, J Thom, G Gilmore, K Loh, Q Yi, C J M Klijn, P Langton, F M van Bockxmeer, R Baker, K Jamrozik
• Journal: Stroke (Stroke) Vol. 36 Issue 1 Pg. 144-6 (Jan 2005) ISSN: 1524-4628 [Electronic] United States
• PMID: 15569860 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers
• Homocysteine
• Vitamin B Complex
• Folic Acid
• Pyridoxine
• Vitamin B 12

Topics

• Biomarkers (blood)
• Blood Coagulation
• Cardiovascular Diseases (etiology)
• Endothelium, Vascular (metabolism)
• Folic Acid (therapeutic use)
• Homocysteine (blood)
• Humans
• Inflammation (blood)
• Ischemic Attack, Transient (blood, drug therapy)
• Pyridoxine (therapeutic use)
• Risk Factors
• Stroke (blood, drug therapy)
• Vitamin B 12 (therapeutic use)
• Vitamin B Complex (therapeutic use)