This study aims to assess the causal relationship between serum homocysteine concentration and cardiovascular diseases, including ischemic heart disease, deep vein thrombosis, pulmonary embolism, and stroke. The researchers conducted meta-analyses of two types of studies: (1) 72 studies that examined the prevalence of the MTHFR gene mutation in cases and controls, and (2) 20 prospective studies of serum homocysteine levels and disease risk. The main outcome measures were odds ratios for a 5 μmol/l increase in serum homocysteine concentration. The results showed significant associations between homocysteine and these diseases. For ischemic heart disease, the odds ratios were 1.42 (95% CI 1.11 to 1.84) in genetic studies and 1.32 (1.19 to 1.45) in prospective studies. For deep vein thrombosis with or without pulmonary embolism, the odds ratios were 1.60 (1.15 to 2.22) in genetic studies. For stroke, the odds ratios were 1.65 (0.66 to 4.13) in genetic studies and 1.59 (1.29 to 1.96) in prospective studies. The study concludes that both genetic and prospective studies provide strong evidence of a causal relationship between homocysteine and cardiovascular disease. Lowering homocysteine concentrations by 3 μmol/l, achievable through increased folic acid intake, is estimated to reduce the risk of ischemic heart disease by 16%, deep vein thrombosis by 25%, and stroke by 24%.This study aims to assess the causal relationship between serum homocysteine concentration and cardiovascular diseases, including ischemic heart disease, deep vein thrombosis, pulmonary embolism, and stroke. The researchers conducted meta-analyses of two types of studies: (1) 72 studies that examined the prevalence of the MTHFR gene mutation in cases and controls, and (2) 20 prospective studies of serum homocysteine levels and disease risk. The main outcome measures were odds ratios for a 5 μmol/l increase in serum homocysteine concentration. The results showed significant associations between homocysteine and these diseases. For ischemic heart disease, the odds ratios were 1.42 (95% CI 1.11 to 1.84) in genetic studies and 1.32 (1.19 to 1.45) in prospective studies. For deep vein thrombosis with or without pulmonary embolism, the odds ratios were 1.60 (1.15 to 2.22) in genetic studies. For stroke, the odds ratios were 1.65 (0.66 to 4.13) in genetic studies and 1.59 (1.29 to 1.96) in prospective studies. The study concludes that both genetic and prospective studies provide strong evidence of a causal relationship between homocysteine and cardiovascular disease. Lowering homocysteine concentrations by 3 μmol/l, achievable through increased folic acid intake, is estimated to reduce the risk of ischemic heart disease by 16%, deep vein thrombosis by 25%, and stroke by 24%.