Limits...
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

Flow diagram of study selection process. CHD indicates coronary heart disease; CVD, cardiovascular disease; RCT, randomized controlled trial.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5015297&req=5

jah31707-fig-0001: Flow diagram of study selection process. CHD indicates coronary heart disease; CVD, cardiovascular disease; RCT, randomized controlled trial.

Mentions: The initial literature search identified 1933 abstracts (Figure 1). After screening based on titles and abstracts, 74 articles were selected for detailed evaluation of their full texts. Of those, 30 RCTs met our inclusion criteria and were included in our analysis. Thirteen RCTs were conducted in European countries (United Kingdom, Norway, Netherlands, Italy, Germany, Switzerland, and France), 9 were conducted in the Americas (United States, Canada, and Brazil), 4 were conducted in Asia (China, India, and the Philippines), and 1 was conducted in Australia and New Zealand. Another 3 RCTs were conducted in multiple countries across continents, including the Vitamin Intervention for Stroke Prevention (VISP)19 in 3 countries across 2 continents, the 2 Heart Outcomes Prevention Evaluation (HOPE)17 studies in 13 countries across 3 continents, and the VITAmins TO Prevent Stroke trial (VITATOPS)37 in 20 countries across 4 continents (Tables 1 and 2).37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51


Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta ‐ Analysis of Randomized Controlled Trials
Flow diagram of study selection process. CHD indicates coronary heart disease; CVD, cardiovascular disease; RCT, randomized controlled trial.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

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

jah31707-fig-0001: Flow diagram of study selection process. CHD indicates coronary heart disease; CVD, cardiovascular disease; RCT, randomized controlled trial.
Mentions: The initial literature search identified 1933 abstracts (Figure 1). After screening based on titles and abstracts, 74 articles were selected for detailed evaluation of their full texts. Of those, 30 RCTs met our inclusion criteria and were included in our analysis. Thirteen RCTs were conducted in European countries (United Kingdom, Norway, Netherlands, Italy, Germany, Switzerland, and France), 9 were conducted in the Americas (United States, Canada, and Brazil), 4 were conducted in Asia (China, India, and the Philippines), and 1 was conducted in Australia and New Zealand. Another 3 RCTs were conducted in multiple countries across continents, including the Vitamin Intervention for Stroke Prevention (VISP)19 in 3 countries across 2 continents, the 2 Heart Outcomes Prevention Evaluation (HOPE)17 studies in 13 countries across 3 continents, and the VITAmins TO Prevent Stroke trial (VITATOPS)37 in 20 countries across 4 continents (Tables 1 and 2).37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51

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