Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

Wang, Xiaobin; Demirtaş, Hakan; Li, Jianping; Mao, Guangyun; Huo, Yong; Sun, Ning; Liu, Lisheng; Xu, Xiping

doi:10.1016/s0140-6736(07)60854-x

Cited by 515 publications

(390 citation statements)

References 41 publications

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“…In contrast, the recently reported improvement in stroke mortality observed after folic acid fortification in the United States and Canada, but not in England and Wales (where fortification is not mandatory), is consistent with the hypothesis that folic acid fortification helps to reduce deaths from stroke (8) . These findings are supported by a recent meta-analysis, showing that folic acid supplementation can effectively reduce the risk of stroke in primary prevention (9) . Thus, the homocysteine hypothesis in CVD is not dead (10) , and the precise mechanism by which hyperhomocysteinaemia is related to atherogenesis needs to be further elucidated.…”

supporting

confidence: 58%

Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic subjects: effect of treatment with B-vitamins

et al. 2009

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Homocysteine has been related to increased risk of CVD. Matrix degradation and inflammation may be involved in this link between hyperhomocysteinaemia and CVD. Recent studies suggest that cystatin C can modulate matrix degradation and inflammation. The present study measured cystatin C at protein (plasma) and mRNA levels (peripheral blood mononuclear cells (PBMC)) in hyperhomocysteinaemic individuals (n 37, female seven and male thirty, aged 20-70 years) before and after B-vitamin supplementation for 3 months in a randomised, placebo-controlled double-blind trial. In a cross-sectional study, seventeen of the hyperhomocysteinaemic subjects were age-and sex-matched to healthy controls (n 17). Our main findings were: (i) as compared with controls, hyperhomocysteinaemic subjects tended to have higher plasma concentrations of cystatin C and lower mRNA levels of cystatin C in PBMC; (ii) compared with placebo, treatment of hyperhomocysteinaemic individuals with B-vitamins significantly increased plasma levels of cystatin C and mRNA levels of cystatin C in PBMC; (iii) while plasma levels of cystatin C were positively correlated with plasma levels of TNF receptor-1, mRNA levels of cystatin C in PBMC were inversely correlated with this TNF parameter. Taken together, our findings suggest that disturbed cystatin C levels may be a characteristic of hyperhomocysteinaemic individuals, potentially related to low-grade systemic inflammation in hyperhomocysteinaemic subjects, and that B-vitamins may modulate cystatin C levels in these individuals. Homocysteine: B-vitamins: Cystatin C: Inflammation: AtherosclerosisEpidemiological studies have established that elevated plasma levels of homocysteine are associated with an increased risk of ischaemic stroke, myocardial infarction and venous thromboembolism (1 -3) . In addition, animal models of hyperhomocysteinaemia have shown abnormalities of vascular structure and function (4) . Paradoxically, however, clinically controlled trials failed to show that lowering homocysteine with vitamin B therapy as secondary prevention reduced risk of CVD or mortality (5 -7) . In contrast, the recently reported improvement in stroke mortality observed after folic acid fortification in the United States and Canada, but not in England and Wales (where fortification is not mandatory), is consistent with the hypothesis that folic acid fortification helps to reduce deaths from stroke (8) . These findings are supported by a recent meta-analysis, showing that folic acid supplementation can effectively reduce the risk of stroke in primary prevention (9) . Thus, the homocysteine hypothesis in CVD is not dead (10) , and the precise mechanism by which hyperhomocysteinaemia is related to atherogenesis needs to be further elucidated.Inflammation and matrix degradation play important roles in the pathogenesis of atherosclerosis and plaque destabilisation. Previously, we have shown that hyperhomocysteinaemic subjects are characterised by raised serum levels of inflammatory cytokines and matrix metalloproteinases...

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supporting

confidence: 58%

Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic subjects: effect of treatment with B-vitamins

et al. 2009

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“…However, the ongoing Folic Acid and Carotid Intimal Thickness (FACIT) trial has reported significant improvements in cognitive function in subjects aged 50-70 years with baseline elevation of plasma homocysteine concentrations 31 and a useful meta-analysis of eight randomised trials of folic acid supplementation showed reduction in the risk of stroke by 18%. 32 This meta-analysis found a greater beneficial effect if the treatment was for more than 36 months and if plasma homocysteine concentrations were reduced by more than 20%. More information on the primary prevention of cardiovascular disease is needed and it would appear that cardiac disease should be studied separately from cerebral disease.…”

Section: Primary Preventionmentioning

confidence: 83%

Homocysteine, folates, and the eye

Wright

Martin

Dodson

2007

Eye

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“…Thus, our finding that men with CHD were significantly more likely to take folic acid supplements one to four times per d is of interest because this may help reduce risk of stroke in the future. To date, studies have shown that a higher intake of folic acid from diet or supplements may help reduce risk of stroke and stroke-related mortality in primary prevention (22,24,25) . However, its role in preventing recurrent stroke and CHD and death in patients with a history of stroke remains unclear (19,36) and requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Folic acid fortification of flour and cereal grain initiated in 1998 may have contributed to this decline (21) . In addition, folic acid supplementation could effectively reduce the risk of stroke in primary prevention (22)(23)(24)(25) ; however, its role in the secondary prevention of stroke remains to be elucidated.…”

mentioning

confidence: 99%

The prevalence and correlates of taking folic acid and vitamin supplements among adults aged ≥45 years with CVD

Zhao

Ford

et al. 2010

Public Health Nutr.

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Objective: To examine the prevalence and likelihood of taking folic acid or vitamin supplements among adults with CHD or stroke v. adults without these conditions. Design: A cross-sectional Behavioural Risk Factor Surveillance System survey was conducted in twelve states of the United States and Puerto Rico in 2006. Selfreported data from participants were collected. Setting: The United States. Subjects: US non-institutionalised adults (n 41 792), aged $45 years. Results: Of all participants, 5445 had CHD and 2076 had stroke. Significantly higher percentages of women than men reported taking folic acid or vitamin supplements. After adjustment for potential confounders, women with CHD had a significantly lower adjusted prevalence (AP) and adjusted OR (AOR) than women without CHD for taking folic acid less than one time per d (AP 5 3?9 % v. Keywords Folic acid Vitamins Coronary heart disease StrokeAlthough the mortality rate of patients with CHD has decreased by 52 % in men and 49 % in women from 1980 to 2002 (1) and the mortality rate of stroke decreased by 24?2 % from 1994 to 2004 (2) , the burden of these diseases remains high. Among US adults, the prevalence of CHD was 7?3 % and the prevalence of stroke was 2?6 % in 2005. Hyperhomocysteinaemia is associated with an increased risk for CVD (3)(4)(5) . Results from meta-analyses have shown that for a 5 mmol/l increase in serum homocysteine levels, the risk of myocardial infarction increased by 84 % (5) , the risk of CHD increased by 23-70 % (4) , and the risk of cerebrovascular disease increased by 58-116 % (4) , although prospective studies offer weaker support for this association than case-control studies (4) . A higher intake of folic acid or multivitamins reduces serum homocysteine levels (6,7) and is associated with reduced risk of acute coronary events and myocardial infarction (8)(9)(10)(11) or reduced rates of coronary restenosis and revascularisation in patients with coronary angioplasty (12,13) . However, other studies including recent clinical trials failed to show any beneficial effects on the risk of recurrent CVD or on total CVD or CHD mortality when using folic acid and B vitamins to lower homocyteine levels among patients with pre-existing CVD or renal disease (14)(15)(16)(17) or among people at high risk for CVD (having a history of vascular disease, diabetes or other coronary risk factors) (18,19) .

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Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

Cited by 515 publications

References 41 publications

Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic subjects: effect of treatment with B-vitamins

Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic subjects: effect of treatment with B-vitamins

Homocysteine, folates, and the eye

The prevalence and correlates of taking folic acid and vitamin supplements among adults aged ≥45 years with CVD

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