Saturday, June 09, 2007
folium zuur en stroke (beroerte)
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Meta-Analysis Suggests Folic Acid Reduces Risk for Initial Stroke
Marlene Busko
Medscape Medical News 2007. © 2007 Medscape
June 1, 2007 — A meta-analysis of 8 randomized controlled trials reports that, overall, folic-acid supplementation reduced the risk for a first stroke by 18%. The stroke risk reduction was approximately 25% in subgroups who received supplements for more than 3 years, had blood homocysteine levels that decreased by 20% or more, or lived in regions with no folate grain fortification. There was no significant risk reduction in the corresponding subgroups without these characteristics.
The findings are published in the June 2 issue of the Lancet.
Lead author Xiaobin Wang, MD, from Northwestern University Feinberg School of Medicine, in Chicago, Illinois, told Medscape that as the controversy over folic-acid supplementation in the prevention of cardiovascular disease (CVD) continues to evolve, the group feels that it is important to identify whether a targeted group of individuals might benefit from this "relatively simple, safe intervention." She added: "Our analysis showed that folic-acid supplementation can lower stroke risk. . . . I think we have pretty coherent evidence. We also further demonstrated that certain populations would benefit even more from folic-acid supplementation."
Focus on Stroke
The use of folic-acid supplements to reduce cardiovascular risk remains controversial, the group writes. "The controversy stems from the fact that the efficacy of homocysteine-lowering therapy to reduce cardiovascular risk hasn't been confirmed by randomized trials," said Dr. Wang.
She added that several observations and studies led the group — with researchers in Chicago and China — to investigate whether stroke may be the disease end point that could particularly benefit from folic-acid supplementation.
First, compared with the United States, in China, the incidence of stroke is 3 to 5 times higher, and average blood folic-acid levels are lower and homocysteine levels are higher. Second, an "intriguing" trial in China showed that supplementation with folate and other vitamins and minerals reduced mortality from cerebrovascular disease by 37% (Mark SD et al. Am J Epidemiol. 1996;143:658-664). Third, although the second Heart Outcomes Prevention Evaluation (HOPE-2) study was negative for other cardiovascular end points, it found that folic-acid supplementation reduced stroke risk by 24% (Lonn E et al. N Engl J Med. 2006;354:1567-1577). Finally, a recent study reported that after the 1998 fortification of grain with folic acid in the United States and Canada, the decline in stroke mortality accelerated in the 1998–2002 period (Yang Q et al. Circulation. 2006;113:1335-1343).
The team searched the literature to April 2007, and 8 randomized controlled trials, consisting of 16,841 individuals, met their criteria. In 7 of the 8 trials, patients had no previous stroke.
Pooling the data from the 8 trials, they found that, overall, folate supplements reduced the risk of stroke by 18%, and this vitamin had an even greater effect in certain subgroups.
Relative Risk of Stroke, Subjects Receiving Folic Acid vs Control Subjects
Subgroup*/All Subjects
Relative Risk (95% CI)
P
> 36 months of supplementation
0.71 (0.57 – 0.87)
.001
> 20% homocysteine lowering
0.77 (0.63 – 0.94)
.012
No folic-acid grain fortification
0.75 (0.62 – 0.91)
.003
No history of stroke
0.75 (0.62 – 0.90)
.002
All subjects
0.82 (0.68 – 1.00)
.045
*In the 4 corresponding subgroups (eg, < 36 months supplementation, etc), the relative risk for stroke did not decrease significantly.
More Folate Study Needed
The group writes that the different observations seen with stroke vs CVD might be because stroke is associated with small blood vessel pathology whereas CVD tends to involve larger blood vessels.
Dr. Wang noted that this meta-analysis was not able to determine what dosage of folic acid is best or whether it should be given alone or in combination with 1 of the B vitamins. She added that more studies are needed to establish this and to determine the efficacy and causality of folic-acid supplementation. The trials should be 4 years or longer in populations who have not had strokes and live in regions without fortified grain.
Editorial: "Widespread Use Still Not Recommended"
In an accompanying editorial, Cynthia M. Carlsson, MD, from the University of Wisconsin School of Medicine and Public Health, in Madison, cautions that "although this meta-analysis helps clarify answers to some questions about the role of homocysteine-lowering in CVD prevention, ongoing randomized trials are needed before we can conclude that the benefit of continued use of previously deemed 'safe' vitamin supplements outweighs the risk of other adverse CVD outcomes." She notes that several large randomized trials have shown that lowering homocysteine with folic acid does not improve CVD outcomes, and when it is combined with B vitamins, it may accelerate CVD risk.
She told Medscape: "While [this meta-analysis] raises the question of whether there are certain subgroups of people who would benefit from folic-acid therapy, it still remains controversial, because large clinical trials have shown negative effects of the vitamin. . . . Widespread use is still not recommended for primary stroke prevention because of its possible adverse effects on heart disease outcomes."
She added that it is hoped that the large randomized trials that are still under way will answer some of those questions, "to help us understand which patient who walks in through our clinic door should be treated with folic acid."
Author: "Folate Supplementation Alone Is Not Harmful"
Dr. Wang noted: "Although we didn’t focus on CVD, and we do want to caution others not to generalize our findings to CVD, for stroke, [folic acid] is definitely beneficial, and we don’t believe folate supplementation alone [without the 2 B vitamins] is harmful even among subjects with CVD." She pointed out that the meta-analysis by Bazzano et al (Bazzano LA et al. JAMA. 2006;296:2720-2226), which analyzed 12 randomized trials, did not demonstrate any combined harmful (or beneficial) effect on cardiovascular outcomes. The 2 studies that reported increased cardiovascular risk showed this only in the groups that took all 3 supplements (folate and high doses of vitamins B6 and B12), as Dr. Wang and colleagues noted in an earlier commentary (Wang X et al. N Engl J Med 2006;355:207-209).
She added that they acknowledge that the current analysis is limited by the existing data. "That's why we concluded only that folic acid can reduce the risk of stroke in primary prevention. For primary prevention, we have 7 trials, so we have a good amount of data to pull together to come up with convincing evidence."
Lancet. 2007;369:1876-1882, 1841-1842.
www.medscape.com
To Print: Click your browser's PRINT button.
NOTE: To view the article with Web enhancements, go to:
http://www.medscape.com/viewarticle/557596
Publication Logo
Meta-Analysis Suggests Folic Acid Reduces Risk for Initial Stroke
Marlene Busko
Medscape Medical News 2007. © 2007 Medscape
June 1, 2007 — A meta-analysis of 8 randomized controlled trials reports that, overall, folic-acid supplementation reduced the risk for a first stroke by 18%. The stroke risk reduction was approximately 25% in subgroups who received supplements for more than 3 years, had blood homocysteine levels that decreased by 20% or more, or lived in regions with no folate grain fortification. There was no significant risk reduction in the corresponding subgroups without these characteristics.
The findings are published in the June 2 issue of the Lancet.
Lead author Xiaobin Wang, MD, from Northwestern University Feinberg School of Medicine, in Chicago, Illinois, told Medscape that as the controversy over folic-acid supplementation in the prevention of cardiovascular disease (CVD) continues to evolve, the group feels that it is important to identify whether a targeted group of individuals might benefit from this "relatively simple, safe intervention." She added: "Our analysis showed that folic-acid supplementation can lower stroke risk. . . . I think we have pretty coherent evidence. We also further demonstrated that certain populations would benefit even more from folic-acid supplementation."
Focus on Stroke
The use of folic-acid supplements to reduce cardiovascular risk remains controversial, the group writes. "The controversy stems from the fact that the efficacy of homocysteine-lowering therapy to reduce cardiovascular risk hasn't been confirmed by randomized trials," said Dr. Wang.
She added that several observations and studies led the group — with researchers in Chicago and China — to investigate whether stroke may be the disease end point that could particularly benefit from folic-acid supplementation.
First, compared with the United States, in China, the incidence of stroke is 3 to 5 times higher, and average blood folic-acid levels are lower and homocysteine levels are higher. Second, an "intriguing" trial in China showed that supplementation with folate and other vitamins and minerals reduced mortality from cerebrovascular disease by 37% (Mark SD et al. Am J Epidemiol. 1996;143:658-664). Third, although the second Heart Outcomes Prevention Evaluation (HOPE-2) study was negative for other cardiovascular end points, it found that folic-acid supplementation reduced stroke risk by 24% (Lonn E et al. N Engl J Med. 2006;354:1567-1577). Finally, a recent study reported that after the 1998 fortification of grain with folic acid in the United States and Canada, the decline in stroke mortality accelerated in the 1998–2002 period (Yang Q et al. Circulation. 2006;113:1335-1343).
The team searched the literature to April 2007, and 8 randomized controlled trials, consisting of 16,841 individuals, met their criteria. In 7 of the 8 trials, patients had no previous stroke.
Pooling the data from the 8 trials, they found that, overall, folate supplements reduced the risk of stroke by 18%, and this vitamin had an even greater effect in certain subgroups.
Relative Risk of Stroke, Subjects Receiving Folic Acid vs Control Subjects
Subgroup*/All Subjects
Relative Risk (95% CI)
P
> 36 months of supplementation
0.71 (0.57 – 0.87)
.001
> 20% homocysteine lowering
0.77 (0.63 – 0.94)
.012
No folic-acid grain fortification
0.75 (0.62 – 0.91)
.003
No history of stroke
0.75 (0.62 – 0.90)
.002
All subjects
0.82 (0.68 – 1.00)
.045
*In the 4 corresponding subgroups (eg, < 36 months supplementation, etc), the relative risk for stroke did not decrease significantly.
More Folate Study Needed
The group writes that the different observations seen with stroke vs CVD might be because stroke is associated with small blood vessel pathology whereas CVD tends to involve larger blood vessels.
Dr. Wang noted that this meta-analysis was not able to determine what dosage of folic acid is best or whether it should be given alone or in combination with 1 of the B vitamins. She added that more studies are needed to establish this and to determine the efficacy and causality of folic-acid supplementation. The trials should be 4 years or longer in populations who have not had strokes and live in regions without fortified grain.
Editorial: "Widespread Use Still Not Recommended"
In an accompanying editorial, Cynthia M. Carlsson, MD, from the University of Wisconsin School of Medicine and Public Health, in Madison, cautions that "although this meta-analysis helps clarify answers to some questions about the role of homocysteine-lowering in CVD prevention, ongoing randomized trials are needed before we can conclude that the benefit of continued use of previously deemed 'safe' vitamin supplements outweighs the risk of other adverse CVD outcomes." She notes that several large randomized trials have shown that lowering homocysteine with folic acid does not improve CVD outcomes, and when it is combined with B vitamins, it may accelerate CVD risk.
She told Medscape: "While [this meta-analysis] raises the question of whether there are certain subgroups of people who would benefit from folic-acid therapy, it still remains controversial, because large clinical trials have shown negative effects of the vitamin. . . . Widespread use is still not recommended for primary stroke prevention because of its possible adverse effects on heart disease outcomes."
She added that it is hoped that the large randomized trials that are still under way will answer some of those questions, "to help us understand which patient who walks in through our clinic door should be treated with folic acid."
Author: "Folate Supplementation Alone Is Not Harmful"
Dr. Wang noted: "Although we didn’t focus on CVD, and we do want to caution others not to generalize our findings to CVD, for stroke, [folic acid] is definitely beneficial, and we don’t believe folate supplementation alone [without the 2 B vitamins] is harmful even among subjects with CVD." She pointed out that the meta-analysis by Bazzano et al (Bazzano LA et al. JAMA. 2006;296:2720-2226), which analyzed 12 randomized trials, did not demonstrate any combined harmful (or beneficial) effect on cardiovascular outcomes. The 2 studies that reported increased cardiovascular risk showed this only in the groups that took all 3 supplements (folate and high doses of vitamins B6 and B12), as Dr. Wang and colleagues noted in an earlier commentary (Wang X et al. N Engl J Med 2006;355:207-209).
She added that they acknowledge that the current analysis is limited by the existing data. "That's why we concluded only that folic acid can reduce the risk of stroke in primary prevention. For primary prevention, we have 7 trials, so we have a good amount of data to pull together to come up with convincing evidence."
Lancet. 2007;369:1876-1882, 1841-1842.
# posted by roodbont @ 12:39 PM 
