Hyperhomocysteinemia: a risk factor for arterial and venous thrombotic disease.
Patients with the rare homozygous hereditary defects of homocysteine metabolism that cause severe hyperhomocysteinemia and homocystinuria are at high risk of arterial and venous thrombosis. This prompted studies of the relationship between moderate hyperhomocysteinemia and thrombotic risk in the general population. In the last 2 decades, retrospective case-control studies and prospective cohort studies have demonstrated moderate hyperhomocysteinemia to be a frequent and independent risk factor for premature vascular disease in the coronary, cerebral, and peripheral arteries. More recently, the association of moderate hyperhomocysteinemia with venous thrombosis was shown in patients with early-onset or recurrent disease and in the general population. Genetic and environmental factors act in concert to cause moderate hyperhomocysteinemia. Since inadequate intake of folic acid, vitamin B12, or vitamin B6 are most frequently associated with hyperhomocysteinemia, dietary supplementation of these vitamins could have a tremendous impact on the epidemiology and natural history of arterial and venous thrombotic diseases.