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 ␤-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 Ϫ3 ⅐ kPa Ϫ1) and compliance (CC in mm 2 ⅐ kPa Ϫ1) 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 0.70Ϯ0.09 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 23.5Ϯ6.9 (10 Ϫ3 ⅐ kPa Ϫ1) and 0.9Ϯ0.3 (mm 2 ⅐ kPa Ϫ1 ) 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 ϭ0.02) and in CC in the CFA (R 2 ϭ0.04). In this study, no relationship was found between homocysteine level and the thickness of the arterial wall, with only a marginal influence on stiffness.

A Cross-Sectional Study of the Effects of Type 2 Diabetes and Other Cardiovascular Risk Factors on Structure and Function of Nonstenotic Arteries of the Lower Limb

“…An increase in IMT represents a more diffuse process with smooth muscle proliferation and ground substance accumulation (26). On the other hand, a much higher correlation of LDL cholesterol with carotid IMT than with femoral IMT has been reported in another study (33), again indicating potential regional differences.…”

Increased Levels of Low-Density Lipoprotein Oxidation in Patients with Familial Hypercholesterolemia and in End-Stage Renal Disease Patients on Hemodialysis

“…Cardiovascular disease (CVD) was more frequent in ESRD patients on hemodialysis and in FH than in controls, but the number of CVD events may not fully reflect the severity of the atherosclerotic disease in the patients. Using B-mode ultrasound, a technique that visualizes atherosclerotic changes in the walls of arteries, it has been demonstrated that carotid artery intima-media thickness is markedly increased, plaque is more frequent, and calcified plaque is common in FH and in ESRD (Haraki et al, 2001;Lavrencic et al, 1996;Pannier et al, 2000;Savage et al, 1998;Smilde et al, 1998;Tonstad et al, 1998). Thus, atherosclerotic disease is underestimated in FH and in ESRD if presented as CVD events only.…”

Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults

“…In contrast, ccIMT, evaluated as the thickness of the carotid arterial wall, was unaffected by the relationship between MTHFR C677T genotype and fitness level. Previous studies demonstrated the relationship between ccIMT and homocysteine levels in female smokers (17), whereas no relationship was observed in patients with atherosclerotic disease (28). de Bree et al (10) reported no effect of ccIMT or pulse wave velocity on increases in plasma homocysteine levels in healthy middle-aged French subjects.…”