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

Meta-analyses of the above three diseases using ( a ) 72 studies in which the prevalence of a mutation in the MTHFR gene (which increases homocysteine) was determined in cases (n=16 849) and controls, and ( b ) 20 prospective studies (3820 participants) of serum homocysteine and disease risk. Main outcome measures: Odds ratios of the three diseases for a 5 μmol/l increase in serum homocysteine concentration.

There were significant associations between homocysteine and the three diseases. The odds ratios for a 5 μmol/l increase in serum homocysteine were, for ischaemic heart disease, 1.42 (95% confidence interval 1.11 to 1.84) in the genetic studies and 1.32 (1.19 to 1.45) in the prospective studies; for deep vein thrombosis with or without pulmonary embolism, 1.60 (1.15 to 2.22) in the genetic studies (there were no prospective studies); and, for stroke, 1.65 (0.66 to 4.13) in the genetic studies and 1.59 (1.29 to 1.96) in the prospective studies.