TY - JOUR
T1 - Meta-analysis of folic acid efficacy trials in stroke prevention
T2 - Insight into effect modifiers
AU - Zhao, Min
AU - Wu, Guangliang
AU - Li, Youbao
AU - Wang, Xiaobin
AU - Hou, Fan Fan
AU - Xu, Xiping
AU - Qin, Xianhui
AU - Cai, Yefeng
N1 - Funding Information:
STUDY FUNDiNG The study was supported by the Projects of National Natural Science Foundation of China (grants 81473052, and 81402735); National Science and Technology Major Projects Specialized for Precision Medicine Research during the 13th Five-Year Plan Period (2016YFC0903100); National Key Technologies RandD Program (2016 YFC0904900); NSFC Innovative Group grant (81521003); the Science, Technology and Innovation Committee of Shenzhen (JCYL20130401162636527); the Department of Development and Reform, Shenzhen Municipal Government (grant SFG 20201744); the Special Project on the Integration of Industry, Education and Research of Guangdong Province (2011A091000031); Science and Technology Planning Project of Guangdong Province, China (grant no. 2014B090904040); Science and Technology Planning Project of Guangdong Province, China (grant no. 201604020003); and research grants from the China Postdoctoral Science Foundation (grant no. 2016M592513).
Publisher Copyright:
© 2017 American Academy of Neurology.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/5/9
Y1 - 2017/5/9
N2 - Objective: To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials. Methods: Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model. Findings: Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84-0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67-0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90-1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77-0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90-1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69-0.88) or low baseline Vitamin B 12 levels (<384 pg/mL: 0.78, 0.68-0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of Vitamin B 12, a low prevalence of statin use, but a high prevalence of hypertension. Conclusions: Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low Vitamin B 12 levels.
AB - Objective: To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials. Methods: Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model. Findings: Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84-0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67-0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90-1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77-0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90-1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69-0.88) or low baseline Vitamin B 12 levels (<384 pg/mL: 0.78, 0.68-0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of Vitamin B 12, a low prevalence of statin use, but a high prevalence of hypertension. Conclusions: Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low Vitamin B 12 levels.
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U2 - 10.1212/WNL.0000000000003909
DO - 10.1212/WNL.0000000000003909
M3 - Article
C2 - 28404799
AN - SCOPUS:85019836177
SN - 0028-3878
VL - 88
SP - 1830
EP - 1838
JO - Neurology
JF - Neurology
IS - 19
ER -