Atherosclerosis is preceded by a phase of changes in the arterial wall that could have functional consequences even before the appearance of atheromatous changes. We hypothesized that early alterations of the mechanical properties of the arterial wall could precede clinical and echographic modifications. We used an automatic, computerized, ultrasonic procedure to evaluate geometric and mechanical characteristics of the common carotid artery (CCA) in normotensive children with primary familial class IIA hypercholesterolemia (FH; n=30; mean+/-SD age, 11+/-2 years old; mean+/-SD systolic/diastolic blood pressure, 109+/-9/55+/-7 mm Hg). These subjects were compared with age-matched, nonobese control subjects (n=27; 11+/-3 years old; 112+/-10/55+/-7 mm Hg). Noninvasive ultrasonic measurements were performed by the same investigator to measure the CCA luminal systolic and diastolic diameters and intima-media thickness (IMT). The cross-sectional compliance, cross-sectional distensibility, and the incremental elastic modulus of the CCA wall were then calculated. Finally, we assessed the degree of reactive hyperemia in the brachial artery produced after distal cuff occlusion and release. The changes in brachial arterial diameter in response to reactive hyperemia (endothelium-dependent dilation) and to glyceryltrinitrate (endothelium-independent dilation) were then measured. In patients with FH, we observed a significant reduction of systodiastolic variations in diameter (by 20%, P:<0.001) without a significant difference in IMT. Cross-sectional compliance and cross-sectional distensibility were significantly reduced in FH subjects (by 15%, P:<0.05 and 19%, P:<0.01, respectively). In parallel, the incremental elastic modulus was significantly increased (by 27%, P:<0.01) in children with FH. No correlation was evident between the carotid incremental modulus and either IMT or plasma low density lipoprotein cholesterol level. There was no difference in diameter of the brachial artery at rest in control and FH subjects (3.0+/-0.5 versus 3.0+/-0.4 mm). The reactive hyperemia and glyceryltrinitrate dilation were also similar in the 2 groups. However, the flow-mediated dilation of the brachial artery was smaller in the FH subjects (4.2+/-2.9%) than in controls (9.0+/-3.1%, P:<0.001). In FH, endothelium-dependent dilation was negatively correlated with the plasma low density lipoprotein cholesterol level (P:<0.04). These results indicate that increased stiffness of the CCA wall in children with FH is independent of blood pressure and could be related to endothelial dysfunction. Thus, alterations in CCA wall mechanics could be early and easily measurable markers of atheromatous changes in the arterial wall.