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(Circulation. 1998;98:2276-2281.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Evidence of Carotid Artery Wall Hypertrophy in Homozygous Homocystinuria

Jean-Louis Megnien, MD; Jérôme Gariepy, MD; Jean-Marie Saudubray, MD; Jean-Marc Nuoffer, MD; Nicolas Denarie, MD; Jaime Levenson, MD; ; Alain Simon, MD

From Centre de Médecine Préventive Cardiovasculaire, Hôpital Broussais (J.-L.M., J.G., N.D., J.L., A.S.), and Département de Pédiatrie Clinique et de Génétique, Hôpital Necker (J.-M.S., J.-M.N.), Paris, France.

Correspondence to Professeur Alain Simon, Centre de Médecine Préventive Cardiovasculaire, Hôpital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France.

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 atherogenesis.

Methods and Results—We investigated ultrasonographically the right common carotid artery in 14 subjects with homozygous homocystinuria aged 3 to 34 years (mean, 13 years) and in 15 of their heterozygous 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 calculated from IMT 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-IMC (P<0.05) and smaller diameter (P<0.05), whereas heterozygotes had values similar to their controls. Multivariate analysis of the arterial parameters with age, body surface area (or height), and plasma total homocysteine in the homozygous and heterozygous 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 carotid wall hypertrophy, whereas heterozygous disease was not. Such hypertrophy may reflect a smooth muscle proliferation induced by hyperhomocysteinemia and represent a promising target for testing vascular effects of therapeutic measures to lower homocysteine.

Key Words: homocysteine • atherosclerosis • ultrasonics • carotid arteries

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