Blood Levels of Homocysteine and Increased Risks of Cardiovascular Disease

Abstract

HOMOCYSTINURIA is a rare autosomal recessive condition usually resulting from homozygous deficiency of cystathionine β-synthase, an enzyme required in methionine metabolism for the conversion of homocysteine to cystathionine. Patients with homocystinuria commonly have fasting plasma total homocysteine (sum of free plus protein-bound forms) levels exceeding 250 µmol/L, compared with a reference range of 5 to 15 µmol/L in healthy subjects,^1,2 and are prone to premature atherosclerosis and thromboembolism of the extracranial and intracranial cerebral arteries and veins, the coronary arteries, and the peripheral arteries and veins.^3,4 While other enzymatic defects can also produce homocystinuria, the observation 3 decades ago that vascular disease was common regardless of the source of the defect suggested that homocysteine may be responsible for the vascular abnormality.⁵ Plausible mechanisms to mediate a deleterious effect of high homocysteine level include vascular endothelial dysfunction,^6-9 promotion of oxidation of low-density lipoprotein cholesterol,^10,11 vascular smooth cell proliferation,¹² and coagulation abnormalities.^13-15