Carotid and Femoral Artery Wall Thickness and Stiffness in Patients at Risk for Cardiovascular Disease, With Special Emphasis on Hyperhomocysteinemia

Abstract

Abstract —Recent developments in ultrasound technology enable the noninvasive measurement of structural and functional vessel wall changes. Until now, the effect of homocysteine on the arterial wall has remained unclear: reports on intima-media thickness (IMT) yield conflicting results, whereas data on vessel wall stiffness are lacking. Because several cardiovascular risk factors result in an increased IMT or stiffness, different groups at risk for atherosclerotic disease, with special emphasis on hyperhomocysteinemia, were studied. Nineteen patients homozygous and 14 subjects heterozygous for cystathionine β-synthase (CBS) deficiency, 21 patients with familial hypercholesterolemia (FH), 15 patients with essential hypertension, 20 smokers, and 28 control subjects were studied. The IMT values (both right and left) of the common carotid artery (CCA), bulb (BUL), internal carotid artery (ICA), and common femoral artery (CFA) were measured in millimeters by high-resolution ultrasound (Biosound). The distensibility (DC, in 10 ⁻³ · kPa ⁻¹ ) and compliance (CC in mm ² · kPa ⁻¹ ) coefficients of the CCA (right and left) and CFA (right) were determined by a wall track system (Pie Medical). The mean IMT of the posterior wall in the CCA was 0.70±0.09 mm in healthy controls. For patients with vascular disease, FH, and hypertension and in smokers, the mean CCA IMT was larger, whereas no major differences in IMT were observed in patients either homozygous or heterozygous for CBS deficiency. The DC and CC in the right CCA were 23.5±6.9 (10 ⁻³ · kPa ⁻¹ ) and 0.9±0.3 (mm ² · kPa ⁻¹ ) in healthy subjects, slightly lower in patients homozygous for CBS deficiency, and clearly lower in patients with vascular disease, FH, and hypertension. No positive correlation was found between plasma homocysteine level and either IMT, CC, or DC. Because smoking was a confounder in each risk group, a stepwise regression analysis was carried out to assess the contribution of each risk factor on IMT and arterial wall stiffness. Age explained most of the variation in IMT of the CCA (coefficient of determination R ² of 0.34), whereas R ² values for serum low density lipoprotein cholesterol, smoking (pack-years), and systolic blood pressure were 0.08, 0.07, and 0.06, respectively. Homocysteine did not contribute to variation in IMT in both the CCA and CFA. Age and smoking contributed to the variation in IMT in the CFA. The variation in DC and CC in the right CCA and right CFA could in part be explained by age, low density lipoprotein cholesterol, and blood pressure. Plasma homocysteine concentration explained only a small proportion of the variation in DC in the CCA ( R ² =0.02) and in CC in the CFA ( R ² =0.04). In this study, no relationship was found between homocysteine level and the thickness of the arterial wall, with only a marginal influence on stiffness.