Epidemiologic studies suggest that hyperhomocystinemia may be an independent risk factor for developing athero-thrombotic vascular disease. Although the mechanism for accelerated atherosclerosis is unclear, proposed mecha¬nisms for increased risk of coronary artery disease include endothelial dysfunction and toxicity, induction of vascular smooth muscle cell proliferation, impairment of nitric oxide, increased LDL oxidation, and enhanced thrombosis. Hyperhomocystinemia has not been shown in animals or in humans to cause atheroma formation, which leads to obstructive lesions in coronary arteries, cerebral arteries, the aorta, or vessels leading to the legs. Pathologic lesions in arteries of experimental animals indicate disease diffusely involves the outer layer, the adventitia and the media with little involvement of the intima and without the formation of segmental atheromatous obstructive lesions. The lesion has a more arteriosclerotic nature rather than athero¬sclerotic (see the chapters Arteriosclerosis and Athero-sclerosis/Atherothrombosis).