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Diabetes mellitus and end-stage renal disease are two pathologic entities associated with increased cardiovascular risk. Several studies have shown that arterial stiffness is increased in both cases and contributes to the increased risk. In order to determine the effect of diabetes and renal failure on arterial stiffness, we conducted a case-control study. One hundred and twenty-two diabetic patients were compared to 122 non-diabetic patients matched to the study group for sex, age, mean arterial pressure, number and localisation of the atherosclerotic alterations. Arterial stiffness was assessed by automatic measurement of the aortic pulse wave velocity (PWV) and by measuring the peripheral and carotid pulse pressure (PP) and reflected waves through analysis of the pulse wave using the principle of applanation tonometry. Aortic PWV was significantly higher in the diabetic subgroup as well as PP at the peripheral and central levels for the same age and mean arterial pressure. In addition, renal failure was independently associated with an increased aortic PWV but not PP in the general population. Independent of the degree of renal failure, a fall in the glomerular filtration rate was also associated with increased aortic PWV. No interaction was noted between renal failure and diabetes mellitus. In conclusion, this study shows that diabetic patients have higher arterial stiffness compared to non-diabetic ones having one or more cardiovascular risk factors, manifested by increased aortic PWV and PP. In addition, renal failure, irrespective of its degree and independent of diabetes mellitus, is associated with increased aortic PWV but not PP. [ABSTRACT FROM AUTHOR]

Hereditary paragangliomas are usually benign tumors of the autonomic nervous system that are composed of cells derived from the primitive neural crest. Even though three genes (SDHD, SDHC, and SDHB), which encode three protein subunits of cytochrome b of complex II in the mitochondrial respiratory chain, have been identified, the molecular mechanisms leading to tumorigenesis are unknown. We studied a family in which the father and his eldest son had bilateral neck paragangliomas, whereas the second son had a left carotid-body paraganglioma and an ectopic mediastinal pheochromocytoma. A nonsense mutation (R22X) in the SDHD gene was found in these three affected subjects. Loss of heterozygosity was observed for the maternal chromosome 11q21-q25 within the tumor but not in peripheral leukocytes. Assessment of the activity of respiratory-chain enzymes showed a complete and selective loss of complex II enzymatic activity in the inherited pheochromocytoma, that was not detected in six sporadic pheochromocytomas. In situ hybridization and immunohistochemistry experiments showed a high level of expression of markers of the angiogenic pathway. Real-time quantitative reverse transcriptase (RT)-PCR measurements confirmed that vascular endothelial growth factor and endothelial PAS domain protein 1 mRNA levels were significantly higher (three- and sixfold, respectively) than those observed in three sporadic benign pheochromocytomas. Thus, inactivation of the SDHD gene in hereditary paraganglioma is associated with a complete loss of mitochondrial complex II activity and with a high expression of angiogenic factors.

Elastin is a protein of the extracellular matrix that forms the major component of elastic fibers from the arterial wall thickness and plays an important role in elastic properties of large blood vessels. To study the relationships between the Ser422Gly polymorphism in exon 16 of the gene-encoding elastin and the distensibility of 2 different arteries, the radial artery (a muscular artery) and the common carotid artery (an elastic artery), we studied a cohort of 320 subjects (49+/-12 years of age) without evidence of cardiovascular disease and who had never been treated with cardiovascular drugs. Distensibility and elastic modulus were evaluated for the common carotid and the radial arteries with high-resolution echo-tracking devices (NIUS-02 and Wall Track System). The A-to-G nucleotide change corresponding to the Ser422Gly amino acid change was studied by digestion of polymerase chain reaction products with BstNI. Results indicate that genotype frequencies (AA=10%, AG=51%, GG=39%) were in agreement with the Hardy-Weinberg equilibrium. For the carotid artery, a significant decrease in distensibility was observed in subjects carrying the A allele (with AA+AG genotypes) compared with subjects with the GG genotype (13.8+/-6.4 kPa(-1). 10(-3) versus 15.9+/-6.2 kPa(-1). 10(-3), P<0.01), assuming a dominant effect of the A allele. Moreover, the presence of the A allele was associated with a significant increase in elastic modulus (0.98+/-0.40 kPa. 10(3) in subjects with AA+AG genotypes versus 0.83+/-0.41 kPa. 10(3) in subjects with GG genotypes, P<0.01). Multivariate analysis indicated that these results were observed after adjustment for age, gender, and mean arterial blood pressure (P<0.01). In contrast, no association was found between arterial parameters and genotypes for the radial artery. The 2-way analysis of covariance adjusted for mean arterial blood pressure indicated that the association between the A allele and distensibility of the carotid artery was observed only in subjects >50 years of age, assuming for carotid distensibility a significant age effect (P<0.01), genotype effect (P=0.01), and age-genotype interaction (P=0.04). The present results indicate a relationship between the Ser422Gly polymorphism and the distensibility of elastic arteries but not of muscular arteries and suggest that there is an age-genotype interaction for carotid artery distensibility.

Increased pulse pressure (PP), an independent predictor of cardiovascular risk, may be quantified on the basis of the prevalence of isolated systolic hypertension (ISH) in the population at large. The purpose of this study was to estimate the prevalence of ISH and its relation to age and drug therapy in a large group of outpatient hypertensive subjects in France. Between March and December 1999, 2975 French general practitioners included 17 716 consecutive patients with uncontrolled hypertension (systolic blood pressure [SBP] >140 mm Hg and/or diastolic blood pressure [DBP] >90 mm Hg), either treated or not treated. They were asked to complete a questionnaire concerning associated cardiovascular risk factors and ongoing antihypertensive therapy. Subjects were classified according to 5 age ranges (from 18 to 103 years). In each age range, SBP, DBP, mean blood pressure, and PP were significantly lower (P<0.001) in treated subjects than in untreated subjects, with the exception of PP in subjects >75 years. The latter finding resulted from a significant increase of SBP and PP with age, together with a significant lowering of DBP with age, irrespective of drug treatment. Subsequently, the prevalence of ISH increased with age from 20.4% to 35.2% in men and women. In any given age range, drug therapy for hypertension is associated with marginally lower values of PP. In the studied populations, the increase of PP with age is independent of gender and of the presence of antihypertensive drug treatment, leading to an increased prevalence of ISH and a subsequent increase of cardiovascular risk with age.

Background: The vascular hallmark of subjects with end-stage renal disease is increased arterial stiffness independent of blood pressure, wall stress, and cardiovascular risk factors such as hypertension, plasma glucose and cholesterol, obesity, and tobacco consumption. Whether arterial stiffness and kidney function are statistically associated in subjects with plasma creatinine < or =130 micromol/L has not yet been determined. Material. In 1290 subjects with normal or elevated blood pressure values and plasma creatinine < or =130 micromol/L, subjects were divided into three tertiles according to the calculated creatinine clearance. Blood pressure, aortic pulse wave velocity (PWV), and standard cardiovascular risk factors were determined in parallel. In 112 of the hypertensive subjects, common carotid and radial artery structure and function (high-resolution echo-Doppler techniques) also were measured., Results: From the 1290 subjects, only the low-tertile group presented a significant negative association between PWV and creatinine clearance independently of blood pressure and standard risk factors. This association was stronger in subjects < or =55 years of age. In the 112 hypertensive subjects, carotid compliance was positively correlated to creatinine clearance even after an adjustment for age, gender, and blood pressure. At less than 55 years of age, creatinine clearance represented 20% of the variance of carotid compliance. Such findings were not observed for radial artery compliance., Conclusion: Increased stiffness of central arteries is statistically associated with reduced creatinine clearance in subjects with mild-to-moderate renal insufficiency, indicating that kidney alterations may interact not only with small but also large arteries, and this is independent of age, blood pressure, and standard risk factors.

Chronic changes in large artery blood flow rates induce corresponding adjustments in arterial diameter, but little is known about structural adaptations of the vessel wall in humans. We used a high-resolution echo-tracking system to measure radial artery internal diameter, wall thickness, and mean blood flow on both arms of 11 patients with end-stage renal disease. Measurements were performed on the wrist side of the arteriovenous fistula. The contralateral radial artery was investigated as control. Wall cross-sectional area, circumferential wall stress, and mean wall shear stress were calculated. Results indicate a sixfold increase in blood flow on the side of the arteriovenous fistula compared with the control side, with a 1.4-fold increase in internal diameter. The diameter enlargement was sufficient to normalize wall shear stress. Changes in diameter were not associated with arterial wall hypertrophy because wall cross-sectional area was not increased and rather suggest a "remodeling" of the arterial wall. For the same level of blood pressure, circumferential wall stress was increased on the side of the arteriovenous fistula. These results suggest that the structural adaptations of the arterial wall to a chronic increase in blood flow normalize wall shear stress and overcome stretch-induced changes in the particular circumstance of arteriovenous fistula.

Hypertension is known to decrease arterial distensibility and systemic compliance. However, the arterial tree is not homogeneous, and it has been shown that the medium-size radial artery does not behave like the proximal, elastic, large, common carotid artery. Indeed, radial artery compliance in hypertensive patients (HTs) has been shown to be paradoxically increased when compared with that in normotensive control subjects (NTs) at the same blood pressure level. To determine whether this increase was due to hypertension-related hypertrophy of the arterial wall, radial artery functional and geometric parameters from 22 NTs (mean +/- SD, 44 +/- 11 years) were compared with those from 25 age- and sex-matched never-treated essential HTs (48 +/- 12 years) by using a high-precision ultrasonic, echo-tracking system coupled to a photoplethysmograph (Finapres system), which allows simultaneous arterial internal diameter, intima-media thickness, and finger blood pressure measurements. When the values for HTs were compared with those of NTs at their respective mean arterial pressures, HTs had similar internal diameter (2.50 +/- 0.56 versus 2.53 +/- 0.32 mm, mean +/- SD) and greater intima-media thickness (0.40 +/- 0.06 versus 0.28 +/- 0.05 mm, P < .001) measurements and increased arterial wall cross-sectional areas (3.79 +/- 1.14 versus 2.45 +/- 0.57 mm2, P < .001). Circumferential wall stress was not significantly different between the two groups. Compliance calculated for a given blood pressure, ie, 100 mm Hg (C100), was greater in HTs than NTs (3.46 +/- 2.41 versus 2.10 +/- 1.55 m2.kPa-1 x 10(-8), P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)