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STUDY: people should strongly consider taking additional folic acid
JOURNAL: BMJ 2002;325:1202-1206.
AUTHORS: Dr. Wald
ABSTRACT: Increasing folic acid intake to lower concentrations of homocysteine would significantly reduce the risk for ischemic heart disease, deep vein thrombosis and stroke.
COMMENTARY: For quite some time an association between homocysteine and cardiovascular disease has been recognized, but there has been considerable doubt as to whether this association is causal.
To investigate the causal role of homocysteine in cardiovascular disease, Dr. Wald from Southampton General Hospital, UK, and colleagues performed a meta-analysis of 72 studies in which the prevalence of a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was determined in 16,849 cases and controls.
They also analyzed 20 prospective studies, which included 3820 subjects and measured the relationship between homocysteine and disease risk.
Dr. Wald's team found a significant association between homocysteine and the risk for ischemic heart disease, deep vein thrombosis and stroke. A 5-mol/L increase in homocysteine was associated with an increased risk of ischemic heart disease in both the genetic studies (odds ratio 1.42) and in the prospective studies (odds ratio 1.32).
The same association was seen for deep vein thrombosis with and without pulmonary embolism (odds ratio in genetic studies 1.60; there were no prospective studies), and for stroke (odds ratio 1.65 in the genetic studies and 1.59 in the prospective studies), the researchers report.
Dr. Wald and colleagues conclude that "our results strengthen the evidence that a raised serum homocysteine concentration is a cause of cardiovascular disease."
They base their conclusions on their analysis of both genetic and prospective studies, which while susceptible to different types of error both found similar associations between homocysteine and cardiovascular disease.
They also note that homocystinurias cause high homocysteine levels and a high risk of premature cardiovascular disease, and that "lowering serum homocysteine reduced risk in both a randomized trial in patients with heart disease and in patients with homocystinuria."
They add that "on this basis, lowering homocysteine concentrations by 3 mol/L from current levels (achievable by increasing folic acid intake) would reduce the risk of ischemic heart disease by [an average of] 16%, deep vein thrombosis by 25% and stroke by 24%."
Dr. Wald advises that "people should strongly consider taking additional folic acid to lower their risk of cardiovascular disease." The priority groups are those with existing cardiovascular disease, but all those over 55 years of age should consider taking folic acid to reduce their risk, he added.