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Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta ‐ Analysis of Randomized Controlled Trials

View Article: PubMed Central - PubMed

ABSTRACT

Background: Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.

Methods and results: Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84–0.96; P=0.002) for stroke, 1.04 (95% CI 0.99–1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92–0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P<0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (P=0.006 for interaction) or in trials with larger reduction in homocysteine levels (P=0.009 for interaction).

Conclusions: Our meta‐analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.

No MeSH data available.


Related in: MedlinePlus

Relative risk of CVD in relation to percentage decreases in homocysteine concentration based on 16 trials with full records of homocysteine changes after the intervention. CVD indicates cardiovascular disease.
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jah31707-fig-0006: Relative risk of CVD in relation to percentage decreases in homocysteine concentration based on 16 trials with full records of homocysteine changes after the intervention. CVD indicates cardiovascular disease.

Mentions: In the sensitivity analysis, we did a metaregression analysis of the continuous variables that might potentially affect the treatment effects. We found no statistically significant dose‐response relationships between CVD outcomes and dosage of folic acid, baseline homocysteine levels, baseline mean age, and percentage of men in the trial, average follow‐up time, and number of events in the study, suggesting that none of these factors had a significant impact on the overall meta‐analysis (data not shown). We observed an inverse relation between degree of homocysteine reduction and intervention effect on CVD (Figure 6) with a significant dose‐response association (P=0.037 for metaregression after adjustment of baseline mean age and percentage of men in the trial). We did not, however, observe significant dose‐response associations between degree of homocysteine reduction and risk of stroke or CHD. The exclusion of any single study from the analyses did not appreciably change the summary RRs and between‐study heterogeneity (Table 5).


Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta ‐ Analysis of Randomized Controlled Trials
Relative risk of CVD in relation to percentage decreases in homocysteine concentration based on 16 trials with full records of homocysteine changes after the intervention. CVD indicates cardiovascular disease.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015297&req=5

jah31707-fig-0006: Relative risk of CVD in relation to percentage decreases in homocysteine concentration based on 16 trials with full records of homocysteine changes after the intervention. CVD indicates cardiovascular disease.
Mentions: In the sensitivity analysis, we did a metaregression analysis of the continuous variables that might potentially affect the treatment effects. We found no statistically significant dose‐response relationships between CVD outcomes and dosage of folic acid, baseline homocysteine levels, baseline mean age, and percentage of men in the trial, average follow‐up time, and number of events in the study, suggesting that none of these factors had a significant impact on the overall meta‐analysis (data not shown). We observed an inverse relation between degree of homocysteine reduction and intervention effect on CVD (Figure 6) with a significant dose‐response association (P=0.037 for metaregression after adjustment of baseline mean age and percentage of men in the trial). We did not, however, observe significant dose‐response associations between degree of homocysteine reduction and risk of stroke or CHD. The exclusion of any single study from the analyses did not appreciably change the summary RRs and between‐study heterogeneity (Table 5).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.

Methods and results: Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84–0.96; P=0.002) for stroke, 1.04 (95% CI 0.99–1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92–0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P<0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (P=0.006 for interaction) or in trials with larger reduction in homocysteine levels (P=0.009 for interaction).

Conclusions: Our meta‐analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.

No MeSH data available.


Related in: MedlinePlus