Research - Wald

Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis

Background
Homocysteine is positively associated with the risk of ischaemic disease, deep vein thrombosis, pulmonary embolism and stroke. It is uncertain whether these associations are causal. Resolving the question of causality is important because serum homocysteine can be lowered with folic acid, raising the prospect of a simple and safe means of prevention.

Why did the researchers do this analysis?
To determine whether the association of homocysteine with heart disease, deep vein thrombosis and pulmonary embolism, and stroke is causal and, if so, measure the effect of homocysteine reduction in preventing them.

Who was studied?
The researchers performed meta-analyses of the aforementioned diseases using 72 studies on the MTHFR gene (which increases homocysteine) and 20 prospective studies on serum homocysteine and disease risk.

What did the researchers find?
There were significant associations between homocysteine and ischaemic heart disease, deep vein thrombosis with and without pulmonary embolism, and stroke.

What are the implications of the study?
Strong evidence suggests that the association between homocysteine and cardiovascular disease is causal. On this basis, lowering homocysteine by 3 units from current levels, which is achievable by increasing folic acid intake, would reduce the risk of ischaemic heart disease by 16%, deep vein thrombosis by 25% and stroke by 24%.

Reference: Wald D, et al. Homocysteine and Cardiovascular Disease: evidence on causality from a meta-analysis. BMJ. Volume 325: 23 November 2002.

HOMOCYSTEINE FACT:

Lowering homocysteine concentrations by 3 umol/l from current levels (achievable by increasing folic acid intake) would reduce the risk of ischaemic heart disease by 16%, deep vein thrombosis by 25%, and stroke by 24%.