Meta-analysis of folic acid efficacy trials in stroke prevention

Zhao, Min; Wu, Guangliang; Li, Youbao; Wang, Xiaobin; Hou, Fan Fan; Xu, Xiping; Qin, Xianhui; Cai, Yefeng

doi:10.1212/wnl.0000000000003909

Cited by 41 publications

(37 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[29][30][31] A meta-analysis of relevant trials revealed that most previous trials were conducted in countries with high folic acid consumption [32,33] and that mandatory folate fortification of the grain supply in those countries may have reduced the Hcy levels in the total population and affected the power of the trials to detect a positive effect. Consistently, our recent meta-analysis found that lowering Hcy concentration by folic acid supplementation significantly reduced the progression of carotid intima-media thickness, [34] the risk of cardiovascular diseases in patients with chronic kidney disease, [35] and the risk of stroke, [36] particularly in those without dietary folic acid fortification. More importantly, a positive association was found between reduction in Hcy levels and the beneficial effect associated with folic acid therapy.…”

Section: Discussionsupporting

confidence: 66%

Effect of MTHFR A1298C and MTRR A66G genetic mutations on homocysteine levels in the Chinese population: a systematic review and meta-analysis

Wang

Ouyang

et al. 2017

Journal of Translational Internal Medicine

Self Cite

View full text Add to dashboard Cite

Background and Objectives: The Chinese population typically has inadequate folate intake and no mandatory folic acid fortification. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the two key regulatory enzymes in the folate/ homocysteine (Hcy) metabolism. Hcy has been implicated in the pathogenesis of cardiovascular disease. We conducted a meta-analysis to assess whether the MTHFR gene A1298C and the MTRR gene A66G polymorphisms affect Hcy levels in the Chinese population. Methods: This analysis included 13 studies with Hcy levels reported as one of the study measurements. Summary estimates of weighted mean differences and 95% confidence intervals (CIs) were obtained using random-effect models. Results: Overall, there were no significant differences in Hcy concentrations between participants with the MTHFR 1298 CC (12 trials, n = 129), AA (n = 2166; β, −0.51 μmol/L; 95%CI: −2.14, 1.11; P = 0.53), or AC genotype (n = 958; β, 0.55 μmol/L; 95%CI: −0.72, 1.82; P = 0.40). Consistently, compared to those with the MTRR 66 GG genotype (6 trials, n = 156), similar Hcy concentrations were found in participants with the AA (n = 832; β, −0.43 μmol/L; 95%CI: −1.04, 0.17; P = 0.16) or AG (n =743; β, −0.57 μmol/L; 95%CI: −1.46, 0.31; P = 0.21) genotype. Similar results were observed for the dominant and recessive models. Conclusions: Neither the MTHFR A1298C polymorphism nor the MTRR A66G polymorphism affects Hcy levels in the Chinese population.

show abstract

Section: Discussionsupporting

confidence: 66%

Effect of MTHFR A1298C and MTRR A66G genetic mutations on homocysteine levels in the Chinese population: a systematic review and meta-analysis

Wang

Ouyang

et al. 2017

Journal of Translational Internal Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Secondly, our trial observed folic acid supplement for 5 years, and shortterm follow-up is not easy to get positive results, and longer follow-up is necessary. 23 Lastly, most previous trials were performed in lower cardiovascular risk patients with higher baseline folate levels, and we found that the beneficial reducing PWV effect appeared to be more pronounced in subjects with lower baseline folate levels. The baseline folate levels in the B-PROOF trial were 19 nmol/L, 10 and some previous folic acid supplement trials conducted in high baseline folic acid areas, so they tend to get null results of folic acid supplementation.…”

Section: Discussionmentioning

confidence: 54%

“…Firstly, our study patients are hypertensive patients in the rural areas of China with high level of Hcy. Secondly, our trial observed folic acid supplement for 5 years, and short‐term follow‐up is not easy to get positive results, and longer follow‐up is necessary . Lastly, most previous trials were performed in lower cardiovascular risk patients with higher baseline folate levels, and we found that the beneficial reducing PWV effect appeared to be more pronounced in subjects with lower baseline folate levels.…”

Section: Discussionmentioning

confidence: 81%

The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT

Yang

Zhang

Song

et al. 2018

Cardiovascular Therapeutics

View full text Add to dashboard Cite

Summary Objective In a subgroup analysis of the China Stroke Primary Prevention Trial, we aimed to explore the impact of folic acid supplementation on arterial stiffness and assess the modifying effect of the methylenetetrahydrofolate reductase (MTHFR) gene in Chinese patients with hypertension. Methods This prospective study enrolled 2529 hypertensive Chinese patients. Participants were randomized to receive treatment with either a combination of enalapril and folic acid or enalapril. Brachial‐ankle pulse wave velocity (PWV) was measured by trained medical staff using PWV instruments at both baseline and exit visits, approximately 5 years after enrollment. This trial was registered with clinicaltrials.gov (NCT00794885). Results During the follow‐up, change in folate was significantly and independently correlated with change in ba‐PWV in study patients (β = −1.31, P < 0.001). Individuals with CC genotype had a significantly greater PWV response to folic acid supplementation than did carriers of the T allele (β = −2.79, P < 0.001 for CC homozygotes compared with β = −0.56, P = 0.464 for TT homozygotes). The positive effect of folic acid on improved PWV was modified by the MTHFR genotype (P for interaction = 0.034). Conclusion In a subgroup of Chinese hypertensive patients who had received 5‐year antihypertensive therapy, increases in folate status were associated with higher reductions in PWV, and individuals with the CC genotype showed greatest PWV response to folic acid supplementation.

show abstract

“…The mean tHcy reduction (−1•6 μmol/l) in the CSPPT is relatively small compared with other published trials; we offer the following explanations. First, the CSPPT supplemented with folic acid alone, whereas most other studies combined folate, B 6 and/or B 12 (10)(11)(12) . The addition of other B vitamins may have helped to further lower the tHcy levels in these studies (about 7 % more than folic acid supplementation alone) (13) .…”

Section: Discussionmentioning

confidence: 99%

“…The addition of other B vitamins may have helped to further lower the tHcy levels in these studies (about 7 % more than folic acid supplementation alone) (13) . Second, there are important differences in characteristics between the participants of the CSPPT and those of previously published trials, including younger age, lower percentage of males and relatively higher eGFR levels (10)(11)(12) . We have found that these factors can significantly modify the effect of folic acid supplementation in lowering tHcy.…”

Section: Discussionmentioning

confidence: 99%

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers

Zhang

et al. 2018

Br J Nutr

Self Cite

View full text Add to dashboard Cite

We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60–<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.

show abstract

Meta-analysis of folic acid efficacy trials in stroke prevention

Abstract: 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 levels.

Cited by 41 publications

References 38 publications

Effect of MTHFR A1298C and MTRR A66G genetic mutations on homocysteine levels in the Chinese population: a systematic review and meta-analysis

Effect of MTHFR A1298C and MTRR A66G genetic mutations on homocysteine levels in the Chinese population: a systematic review and meta-analysis

The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers

Contact Info

Product

Resources

About