Abstract-The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityϫblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressureϫinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6Ϯ3.3 dynes/cm 2 (meanϮSD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4Ϯ0.6ϫ10 4 dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (rϭ0.55, PϽ0.0001) and directly associated with circumferential wall tension (rϭ0.43, PϽ0.0001). Shear stress and circumferential wall tension were inversely correlated (rϭ0.66, PϽ0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors. (Hypertension. 1999;34:217-221.) Key Words: carotid arteries Ⅲ atherosclerosis Ⅲ stress, mechanical Ⅲ tensile stress Ⅲ tunica media A therosclerosis is a systemic disease, caused or favored by systemic risk factors, that localizes in particular regions of the arterial tree, probably through interaction with local predisposing factors. 1-2 Among the predisposing factors, the hemodynamic forces (shear stress and tensile stress) generated by flowing blood are of utmost importance. [3][4][5][6] Shear stress is the frictional force that acts tangentially to the endothelial surface. Tensile stress is the circumferential wall tension divided by wall thickness, and it acts perpendicularly to the arterial wall and results from the extensional (dilating) effect of blood pressure on the vessel. These hemodynamic forces also influence the vessel wall structure and development and contribute to the regulation of vascular tone. 5,[7][8][9][10][11] In vitro and in vivo experiments have demonstrated that vessels tend to maintain constant shear stress in response to flow changes. [12][13][14] We have previously demonstrated that common carotid artery shear stress in healthy men in vivo decreases with increasing age, blood pressure, and body mass index (BMI) and that low shear stress values are associated with intima-media thickening, an ech...

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Abstract-Seventy-one mutations of the low density lipoprotein (LDL) receptor gene were identified in 282 unrelated Italian familial hypercholesterolemia (FH) heterozygotes. By extending genotype analysis to families of the index cases, we identified 12 mutation clusters and localized them in specific areas of Italy. To evaluate the impact of these mutations on the clinical expression of FH, the clusters were separated into 2 groups: receptor-defective and receptor-negative, according to the LDL receptor defect caused by each mutation. These 2 groups were comparable in terms of the patients' age, sex distribution, body mass index, arterial hypertension, and smoking status. In receptor-negative subjects, LDL cholesterol was higher (ϩ18%) and high density lipoprotein cholesterol lower (Ϫ5%) than the values found in receptor-defective subjects. The prevalence of tendon xanthomas and coronary artery disease (CAD) was 2-fold higher in receptor-negative subjects. In patients Ͼ30 years of age in both groups, the presence of CAD was related to age, arterial hypertension, previous smoking, and LDL cholesterol level. Independent contributors to CAD in the receptor-defective subjects were male sex, arterial hypertension, and LDL cholesterol level; in the receptor-negative subjects, the first 2 variables were strong predictors of CAD, whereas the LDL cholesterol level had a lower impact than in receptor-defective subjects. Overall, in receptor-negative subjects, the risk of CAD was 2.6-fold that of receptordefective subjects. Wide interindividual variability in LDL cholesterol levels was found in each cluster. Apolipoprotein E genotype analysis showed a lowering effect of the ⑀2 allele and a raising effect of the ⑀4 allele on the LDL cholesterol level in both groups; however, the apolipoprotein E genotype accounted for only 4% of the variation in LDL cholesterol.Haplotype analysis showed that all families of the major clusters shared the same intragenic haplotype cosegregating with the mutation, thus suggesting the presence of common ancestors. (Arterioscler Thromb Vasc Biol. 2000;20:e41-e52.)

We describe a 6-min HPLC method to measure the total concentrations of the most important thiols in plasma and urine–cysteine, homocysteine, cysteinylglycine, and glutathione–as well as the concentrations in plasma and urine, respectively, of cysteamine and 2-mercaptopropionylglycine, two compounds used to treat disorders of cysteine metabolism. Precolumn derivatization with bromobimane and reversed-phase HPLC were performed automatically by a sample processor. Throughput was up to 100 samples in 24 h. The within-run CV ranged from 0.9% to 3.4% and the between-run CV ranged from 1.5% to 6.1%. Analytical recovery was 97–107%, with little difference between plasma and urine samples. The detection limit was ∼50 nmol/L for all the analytes studied. Thiol concentrations were determined in the plasma of 206 healthy donors and in the urine of 318 healthy donors distributed for age and sex. Mean values of plasma cysteine and homocysteine were significantly lower in infants (ages, <1 y) compared with other age groups (P <0.005). In adults, mean plasma homocysteine values were higher in males than in females (9.2 vs 6.7 μmol/L, P <0.0001) and in the 6- to 10-year-old group (P <0.05). Mean values for glutathione and cysteinylglycine were not sex- and age-dependent. In urine, both cysteine and homocysteine showed a wide range of variation.

Background and Purpose-Systemic and local coronary heart disease (CHD) risk factors participate in atherogenesis. The role of wall shear stress, a major local risk factor, remains to be elucidated. Methods-Two hundred thirty-four subjects were carefully characterized for the presence of hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking and were divided into low-and high-risk groups. They underwent echo-Doppler examination of the carotid arteries. Atherosclerotic plaques and stenoses were detected, intima-media thickness (IMT) was measured, and wall shear stress was calculated. Results-One hundred eight subjects were classified as low-risk individuals. The prevalence of carotid atherosclerosis in this group was 18.5%. Wall shear stress was 24.23Ϯ7.21 dyne/cm 2 in individuals without atherosclerosis and 16.89Ϯ5.48 in those with atherosclerosis (PϽ0.000). In multiple regression analyses, wall shear stress, body mass index, and HDL cholesterol were inversely associated and total cholesterol was directly associated with the presence of atherosclerosis; only wall shear stress was associated with IMT. In the high-risk group the prevalence of atherosclerosis was 45.2%. Wall shear stress was 20.44Ϯ6.82 dyne/cm 2 in subjects without atherosclerosis and 17.84Ϯ6.88 dyne/cm