Effect Of B-vitamin Supplementation On Recurrent Stroke For Stroke Patients: A Meta-analysis

Objective: Stroke, as the second most common cause to death and the first to disability in the world, is one of the most endangering diseases, also one of the most serious public health problems in china. Some dangerous factors have been studied and documented, such as age, hypertension, lipid disorder, diabetes, and smoking. Homocysteine(Hcy), a sulfur-containing amino acid, emerges in the metabolism process of methionine which is a kind of essential amino acid. Along with the development of molecular biology technology and the detection level, many studies have showed that high homocysteine level is one of the independent risk factors for atherosclerosis and closely related to the progress of stroke. However, current studies have the conflicting conclusions on whether B vitamins supplementation could prevent the recurrent stroke for stroke patients. Therefore, we conduct a systematic review and meta-analysis on recurrent stroke researches in order to evaluate the possible effect of B-vitamin supplementation.Methods: 1 Search strategy establishment and literature collection. A systematic search was performed on some nets such as Pub Med, Medline, Sciene Direct, Chinese Biomedical Data-Base, China National Knowledge Infrastructure and so on to find documents published in English or Chinese before December 2015 with the keywords “homocysteine” OR “folate” OR “folic acid” OR “vitamin B12” OR “cobalamin” OR “vitamin B6” OR “pyridoxine” OR “vitamin B1” OR “thiamine” AND “randomized controlled trials” AND “clinical trials” AND “human” AND “stroke” OR “cerebral vescular disease” OR “cerebral ischemia” both in English and Chinese.2 Draw up criteria for including and excluding.The followings are including criteria: 1) Research types: randomized controlled trial(RCT); 2) Research subjects: adult patients with stoke; 3) Intervention measures: the B-vitamin therapy in the test group and a placebo or basic therapies without B-vitamins in the controlled group; 4) Following-up visits at least 6 months; 5) Outcomes: recurrence of stroke. The followings are excluding criteria: 1) Experiments on animals, cell experiments or nonprimary literature; 2) Non-randomized controlled trial; 3) Documents can not be made use for incomplete data; 4) the intervention contains B vitamins in control group; 5) Repeated report. 3 Data extraction. Two researchers extracted relevant data independently from the included studies. From each study, the following information was extracted: 1) The basic features of literature: the title, source, the time of publication, country, the name of first author and contact information; 2) age distribution, the number of patients and controlled subjects, intervention measures, the mean follow-up time, rate ratio of recurrent stroke and the levels of homocysteine. The revised Jadad scale(modified Jadad scale) was carried out to assess the quality of each included study, one to three points as the low quality studies, and four to seven points as the high quality research. 4 Statistical analysis. Meta analyses were performed on all of the statistics by STATA12.0. Heterogeneity was examined by Q-test. Fixed-and random-effects models were used to compute summary estimates and the corresponding 95% confidence intervals. To evaluate the potential for publication bias, a visual inspection of asymmetry in funnel plots was performed, and the symmetry of the funnel plot was tested using Egger's test and Begg's test(P < 0.05 was considered to be a representative of statistically significant publication bias). We also conducted a sensitivity analysis in which one study was removed and the rest were analysed to confirm the stability of the overall results.Results: 1 Literature retrieval results. We identified 238 potential relevant studies by a primary computerized literature search. After screening titles and abstracts and reviewing the full-text articles, at last, 7 studies including 6 Chinese literature and 1 English literature were obtained. 2 Meta-analysis results. Heterogeneity test results showed that I2=62.9%, P=0.009, therefore random effect model was employed. It reveals that the pooled relative risk(RR) was 0.64 with 95% confidence interval(CL)(0.47, 0.87). Cumulative Meta analysis showed that, from the beginning of 2012, B-vitamin showed the effect of stroke prevention in patients with stroke, and the confidence interval tended to be stable, which was a good change trend. We detected publication bias in the literature based on either Egger's test(P=0.008) or Begg's test(P=0.035). In the sensitivity analyses, there was no significant variation in the pooled RR by excluding any of the studies, supporting the robustness of our results. With vitamin B supplements, the level of plasma homocysteine in experimental group was decreased by 5.24?mol/L compared with the control group and 95% CL(-5.60,-4.87). It showed that B-vitamin can significantly reduce the plasma homocysteine level.Conclusions: 1 B-vitamin supplementation may prevent the recurrence of stroke for the stroke patients. It plays an important role in the secondary prevention of stroke. 2 B-vitamin supplementation couldsignificantly reduce the level of plasma homocysteine for the stroke patients.