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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 |
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| Authors: | Kathleen Potter Graeme J Hankey Daniel J Green John Eikelboom Konrad Jamrozik Leonard F Arnolda |
| Institution: | 1. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia 2. Department of Neurology, Royal Perth Hospital, Perth, Australia 3. School of Sport Science, Exercise and Health, University of Western Australia, Perth, Australia 4. Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK 5. Department of Medicine, McMaster University, Hamilton, Canada 6. School of Population Health and Clinical Practice, University of Adelaide, Adelaide, Australia 7. Department of Cardiology, Royal Perth Hospital, Perth, Australia |
| Abstract: | BackgroundExperimental 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.MethodsWe 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.ResultsAfter 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 μmol/L, 95% CI 7.5 to 8.4 versus 11.8 μmol/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.ConclusionAlthough 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.Trial RegistrationClinical Trial Registration URL: http://www.actr.org.au/ Trial Registration number: 12605000005651 |
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