EVIDENCE OF CAROTID-ARTERY WALL HYPERTROPHY IN HOMOZYGOUS HOMOCYSTINURIA

Background-We aimed to determine whether intima-media thickness (IMT) was increased in the carotid artery of subjects with homocystinuria to better understand the in vivo contribution of homocysteine to early a therogenesis. Methods and Results-We investigated ultrasonographically the right common carotid artery in 14 subjects with homozygous homocy stinuria aged 3 to 34 years (mean, 13 years) and in 15 of their hetero zygous parents aged 32 to 47 years (mean, 41 years) by comparison with 2 control groups of 15 healthy subjects of the same age. Far-wall IMT and lumen diameter were measured with a computerized program, and the cross-sectional area of the intima-media complex (CSA-IMC) was calcul ated from WIT and diameter. Comparison with their respective controls, adjusted for body surface area or height, showed that homozygotes had greater IMT (P<0.001) and CSA-LMC (P<0.05) and smaller diameter (P<0. 05), whereas heterozygotes had values similar to their controls. Multi variate analysis of the arterial parameters with age, body surface are a (or height), and plasma total homocysteine in the homozygous and het erozygous groups combined showed that IMT was related to age (P<0.05) and homocysteine (P<0.01), diameter was related to body surface area ( P<0.001) or height (P<0.05), and CSA-IMC was related to age (P<0.05), body surface area (P<0.05) (but not height), and homocysteine (P<0.05) . Conclusions-Homozygous homocystinuria was associated with common car otid wall hypertrophy, whereas heterozygous disease was not. Such hype rtrophy may reflect a smooth muscle proliferation induced by hyperhomo cysteinemia and represent a promising target for testing vascular effe cts of therapeutic measures to lower homocysteine.