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Pierre Boutouyrie

Publications and source records attributed to Pierre Boutouyrie.

33 records · Page 2Linked to original sources
PubMed2004

Glucose level is a major determinant of carotid intima-media thickness in patients with hypertension and hyperglycemia.

BACKGROUND: A causal relationship has been established between hyperglycemia and cardiovascular diseases, but no threshold has been retained to determine a 'glycemia-associated' cardiovascular risk. Carotid intima-media thickness (CIMT) is an independent predictor for cardiovascular events. High blood pressure is a major determinant of CIMT. OBJECTIVES: To determine the influence of fasting glycemia on CIMT in hypertensive patients with either normal fasting glucose, impaired fasting glucose (IFG) or type 2 diabetes (DM-2). METHODS: We included 158 essential hypertensive patients with either normal fasting glucose (n=74), IFG (n=24) or DM-2 (n=60) in a cross-sectional study. Common carotid IMT was measured with a high resolution echotracking system. RESULTS: CIMT of DM-2 patients was significantly higher than that of IFG and normal fasting glucose patients (809 +/- 180, 697 +/- 151 and 689 +/- 134 microm, respectively; analysis of variance (ANOVA) P <0.0001). In multivariate analysis in normal fasting glucose patients, local pulse pressure and age were the major determinants of CIMT, whereas glycemia was not. In IFG and DM-2 patients, fasting glycemia was strongly associated with CIMT, explaining 21 and 18% of its variance, respectively. Particularly, in IFG patients, an increase in 1 mmol/l glycemia was associated with a 165 microm increase in CIMT. In hyperglycemic patients, with either IFG or DM-2, age was an important determinant of CIMT, whereas local pulse pressure was not. CONCLUSION: These data suggest that glycemia is a major independent determinant of CIMT in hypertensive hyperglycemic patients, not only in DM-2 patients but also at the earlier stage of IFG, offsetting the mechanical role of local pulse pressure.

Aged↗
PubMed2004

Compliance with methadone-based substitutive treatment: a proposed model based on immunoassay urinary sample screening.

Methadone (MTD) maintenance treatment is a recognized method to reduce illicit opiate abuse. Because of the difficulties of collecting 24-hour urines routinely, the monitoring of MTD compliance is currently done with random urinary screening. However, monitoring of MTD compliance by random urinary screening lacks accuracy because of its highly variable pharmacokinetics, leading to false positive or negative results. This study's objective was to identify factors influencing the reliability of urinary screening of methadone for MTD compliance monitoring in a field setting involving usual care for opiate-dependent patients. In a cross-sectional population-based study, 1981 urine samples obtained from 68 patients in parallel with drug dose, gender, and weight were analyzed by MTD enzyme immunoassay (EMIT). Urinary pH was measured, and positive threshold was determined experimentally by box-plot analysis. Multivariate determinants of MTD excretion were established with stepwise multiple regression analysis. On this basis, adjusted values for MTD excretion were proposed and verified with an (S)-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) assay from independent urine samples that were negative or doubtful by the MTD assay. MTD excretion was higher in men, decreased with increased urinary pH, and increased with daily dosage of MTD; these factors explain 32% of the total variance of urinary MTD. Adjustment on these 3 variables (urinary pH, sex, daily dosage) improved the prediction of compliance to MTD treatment. Threshold was stable across pH values and in agreement with EDDP results. The influence of simple variables such as gender, urinary pH, and daily dosage on urinary MTD excretion could be put in evidence and accounted for. Adjusted values of urinary MTD are more reliable than the raw values for monitoring compliance to MTD treatment.

Adult↗
PubMed2004

Arterial stiffness and angiotensinogen gene in hypertensive patients and mutant mice.

OBJECTIVE: To determine whether carotid artery stiffness was increased in patients with untreated essential hypertension who are homozygous for the T allele of the M235T polymorphism of the angiotensinogen (AGT) gene and in mutant mice carrying three copies of the angiotensinogen (Agt) gene. METHODS: Using echotracking systems, we studied carotid mechanical properties in 98 never-treated hypertensive patients according to their AGT genotype, and in Agt mutant mice. RESULTS: Patients homozygous for the T allele had a reduced carotid distensibility and an increased stiffness of the carotid wall material (Young's elastic modulus), independent of blood pressure, compared with patients homozygous for the M allele. In Agt1/2 mice, carotid distensibility was not significantly different from that of Agt1/1 (wild-type). Moreover, the stiffness of the arterial wall material was lower in Agt1/2 mice than in wild-type mice. In Agt1/2 mice, the greater blood pressure was not associated with arterial hypertrophy, resulting in a greater circumferential wall stress. The in-vivo and in-vitro pressor responses to angiotensin II were reduced in Agt1/2 mice, whereas the contractile response to phenylephrine was not significantly different between Agt1/1 and Agt1/2 mice, indicating the integrity of the contractile apparatus and suggesting a dysfunction of the angiotensin II type 1 receptor signalling pathways in Agt1/2 mice. CONCLUSION: These data suggest that the angiotensinogen TT genotype at position 235 could be a genetic marker for arterial stiffness in patients with never-treated hypertension, whereas in Agt1/2 mice the dysfunction of the angiotensin II type 1 receptor signalling pathways could explain the lack of arterial wall hypertrophy and stiffness.

Adult↗
PubMed2004

Rationale, design and methods of the CASHMERE study.

Carotid intima-media thickness (IMT) measurement is a noninvasive method used for quantification of early stage of atherosclerosis. Data suggest that the combination of statin and hormone replacement therapy (HRT) might be useful in reducing the early progression of atherosclerosis in postmenopausal women. The main aim of the study is to compare the effects of 12-month therapy with atorvastatin (80 mg/day), HRT (oral 17beta-estradiol 1 or 2 mg/day, plus cyclic dydrogesterone 10 mg) alone and their combination vs. placebo on the progression of carotid IMT by using a high-definition echotracking device. The secondary objectives are to assess the effects of the treatments vs. placebo on arterial stiffness, lipid profile and C-reactive protein. The CASHMERE trial is an European randomized study with a 2 x 2-factorial design, double blinded for atorvastatin and prospective randomized, open blinded endpoint evaluation (PROBE) method applied to HRT. The investigators can adjust the dose of estradiol at any time during follow-up if necessary. A total of 800 postmenopausal women with mild hypercholesterolemia and with no previous history of cardiovascular disease will be included and followed up by their physicians [general practitioners (GPs) or gynecologists] for 1 year. The CASHMERE trial is the first randomized clinical trial to examine the effects of a statin alone or combined with HRT on the structure and the function of carotid artery as early markers of atherosclerosis in postmenopausal women with mild hypercholesterolemia. The results are expected for 2007.

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PubMed2003

Physiological genomics of human arteries: quantitative relationship between gene expression and arterial stiffness.

BACKGROUND: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters. METHODS AND RESULTS: In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell. CONCLUSIONS: Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.

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PubMed2003

Aortic stiffness is an independent predictor of fatal stroke in essential hypertension.

BACKGROUND AND PURPOSE: Pulse pressure is a stronger predictor of cardiovascular events than systolic or diastolic blood pressure in large cohorts of French and North American patients. However, its influence on stroke is controversial. Large-artery stiffness is the main determinant of pulse pressure. The influence of arterial stiffness on the occurrence of stroke has never been demonstrated. Our aim was to establish the relationship between aortic stiffness and stroke death in hypertensive patients. METHODS: We included, in a longitudinal study, 1715 essential hypertensive patients who had a measurement of arterial stiffness at entry (ie, between 1980 and 2001) and no overt cardiovascular disease or symptoms. Mean follow-up was 7.9 years. At entry, aortic stiffness was assessed from the carotid-femoral pulse wave velocity. A Cox proportional hazard regression model was used to estimate the relative risk (RR) of stroke and coronary deaths. RESULTS: Mean+/-SD age at entry was 51+/-13 years. Twenty-five fatal strokes and 35 fatal coronary events occurred. Pulse wave velocity significantly predicted the occurrence of stroke death in the whole population. There was a RR increase of 1.72 (95% CI, 1.48 to 1.96; P<0.0001) for each SD increase in pulse wave velocity (4 m/s). The predictive value of pulse wave velocity remained significant (RR=1.39 [95% CI, 1.08 to 1.72]; P=0.02) after full adjustment for classic cardiovascular risk factors, including age, cholesterol, diabetes, smoking, mean blood pressure, and pulse pressure. In this population, pulse pressure significantly predicted stroke in univariate analysis, with a RR increase of 1.33 (95% CI, 1.16 to 1.51) for each 10 mm Hg of pulse pressure (P<0.0001) but not after adjustment for age (RR=1.19 [95% CI, 0.96 to 1.47]; P=0.10). CONCLUSIONS: This study provides the first evidence, in a longitudinal study, that aortic stiffness is an independent predictor of fatal stroke in patients with essential hypertension.

Adult↗
PubMed2003

Arterial remodeling and stiffness in patients with pseudoxanthoma elasticum.

OBJECTIVE: Proteoglycans organize the extracellular matrix, act as signaling molecules, and are involved in cell migration and proliferation. They may play an important role in arterial geometric and elastic properties. The aim of the present study was to determine large artery phenotype in patients with pseudoxanthoma elasticum (PXE), a genetic disease characterized by proteoglycan accumulation and fragmented elastic fibers in connective tissues. METHODS AND RESULTS: In 27 patients with PXE (25 females and 2 male) and 27 control subjects matched by age, sex, and blood pressure, we noninvasively determined the common carotid and radial artery diameter, intima-media thickness (IMT), and distensibility with high-definition echo-tracking systems and applanation tonometry. Patients with PXE had a significantly higher carotid IMT (611+/-106 versus 520+/-76 microm, P<0.001) independently of body surface area, age, and mean blood pressure. The increase in carotid IMT predominated in older patients with PXE at the time of examination. No significant difference in carotid elastic properties was observed between patients with PXE and control subjects. At the site of the radial artery, distensibility was significantly higher in patients with PXE than in control subjects (11.6+/-11.4 versus 5.9+/-3.4 kPa(-1) x 0.10(-3); P=0.02) and internal diameter was lower (1.66+/-0.51 versus 2.07+/-0.36 mm; P<0.01) without change in intima-media thickness and Young's elastic modulus. CONCLUSIONS: Phenotypic changes of superficial arteries in patients with PXE were represented by a thickening of the carotid artery and a reduced stiffness of the radial artery and predominated in older female patients.

Adult↗
PubMed2003

Angiotensinogen gene M235T polymorphism and reduction in wall thickness in response to antihypertensive treatment.

The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. Carotid intima-media thickness (IMT) is an early marker of atherosclerosis. The objectives of the present study were to determine in previously untreated essential hypertensive patients whether carotid IMT was associated with the M235T polymorphism, and to determine whether the M235T polymorphism could influence the reduction of carotid IMT by antihypertensive treatment. Common carotid artery IMT was determined with a high-definition echotracking system in 98 previously untreated hypertensive patients in a cross-sectional study. A subgroup of 56 patients was included in a randomized double-blind parallel group study comparing the effect of the angiotensin-converting-enzyme-inhibitor enalapril with that of the beta-blocker celiprolol during a 5 month period. In the cross-sectional study, a multivariate analysis showed that the M235T genotype was a significant independent determinant of carotid IMT, explaining 7% of the variance. Carotid IMT was higher in patients homozygous for the T allele than in MM patients. In the longitudinal study, the reduction in carotid IMT after antihypertensive treatment was significantly ( P <0.01) higher in patients carrying the TT genotype than in patients carrying the MM genotype, despite similar reductions in blood pressure and independently of drug type. In conclusion, these data suggest that the angiotensinogen TT genotype at position 235 is a genetic marker for early carotid atherosclerosis in a hypertensive population and its regression under antihypertensive treatment.

Adult↗
PubMed2003

Evidence for carotid and radial artery wall subclinical lesions in renal fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FD) is a non-atherosclerotic, non-inflammatory arterial disease of unknown cause, and most frequently affects the renal and internal carotid arteries. Our objectives were to determine whether quantitative and qualitative lesions could be detected by high-resolution echotracking techniques at two arterial sites generally considered as free of echographic lesions: the common carotid and the radial arteries, and to compare their frequency with a control population. METHODS AND RESULTS: We studied 70 patients with renal FD and 70 control subjects matched for age, sex and systolic blood pressure. Arterial parameters were determined using non-invasive high-resolution echotracking systems. Carotid B-mode scans and radiofrequency signals were analysed and quoted by three observers blinded to diagnosis. FD patients had thicker carotid (+12%, P < 0.001) and radial arteries (+10%, P < 0.05) than controls. Abnormal echographic patterns of the carotid artery, including supernumerary interfaces and/or interruption of the blood-intima acoustic interfaces, were frequently observed in FD patients and rarely in control subjects. These abnormalities were quantified with a phenotypic score ranging from 2 to 7, and their sensitivity and specificity were 73 and 81%, respectively, as markers of FD. Having a phenotypic score > 3 conferred an odds ratio of 12.9 (95% CI 5.7-29.3) of having renal FD. CONCLUSION: We defined a new carotid phenotype in FD patients using a non-invasive echotracking system, and showed an increased wall thickness and distensibility of the radial artery. These data indicate the presence of subclinical lesions at arterial sites distant from the renal arteries, suggesting that renal FD is not a focal but a systemic arterial disease.

Adult↗
PubMed2002

Homocysteine is the only plasma thiol associated with carotid artery remodeling.

Several authors have reported that moderate hyperhomocysteinemia is related to asymptomatic carotid arterial wall remodeling, but few data are available on other thiol compounds with potential vascular toxicity. We, therefore, investigated the relationships between major plasma thiol compounds (homocysteine, cysteine and glutathione) and the structural phenotype of the common carotid artery in a cohort of 123 subjects with no evidence of cardiovascular disease. Fasting levels of thiol compounds were measured by high-performance liquid chromatography, and arterial geometry was evaluated using high-resolution echotracking devices. In univariate regression analysis, plasma homocysteine and plasma cysteine concentrations were positively associated with carotid artery internal diameter (P=0.0001 and 0.002, respectively) and intima media thickness (P=0.003 and 0.004), but the plasma glutathione concentration was not. In multivariate analysis, plasma homocysteine was independently and positively associated with carotid artery internal diameter (P<0.005) and intima media thickness (P<0.05), but plasma cysteine was not. These data suggest that homocysteine is the only plasma thiol compound that may be considered as a risk factor for preclinical cardiovascular disease.

Adult↗
PubMed2002

Disruption of the elastin gene in adult Williams syndrome is accompanied by a paradoxical reduction in arterial stiffness.

Although the aetiology of Williams syndrome (WS) is related to elastin gene disruption, its pathogenesis remains unknown, particularly that of vascular lesions. The aim of the present study was to compare the elastic properties of three WS patients with age- and gender-matched normotensive and hypertensive controls. Common carotid arteries of WS patients had a higher distensibility, a thicker intima-media and a lower elastic modulus. Electron microscopy studies of one WS renal artery showed major abnormalities of the elastic fibres, which displayed a reticular structure and a thickening of the internal elastic lamina, whereas the ultrastructure of elastic fibres was normal in a control subadventitial muscular fibrodysplasia. In this WS arterial stenosis, we studied the expression patterns of several major smooth muscle (SM) phenotypic markers using immunofluorescence and used a normal renal artery as a control. In WS, SM-alpha-actin- and myosin-heavy-chain-positive cells contained low amounts of heavy caldesmon, and laminin-beta1 chain was expressed into the basement membranes, indicating a less differentiated phenotype. In conclusion, in WS patients, the carotid artery wall was abnormally distensible and thick, and major ultrastructural abnormalities of elastic fibres were observed in association with smooth muscle cell de-differentiation. These results indicate that the haplo-insufficiency of the elastin gene in WS patients leads to abnormal elastic fibre assembly within the media. Arterial wall hypertrophy found with a primary defect in elastin may represent a major factor responsible for increased distensibility. We suggest that, in WS, the increased proliferative response and the associated de-differentiation process represent two important mechanisms underlying the matrix accumulation and the development of arterial stenosis.

Adult↗
PubMed2002

Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study.

Arterial stiffness may predict coronary heart disease beyond classic risk factors. In a longitudinal study, we assessed the predictive value of arterial stiffness on coronary heart disease in patients with essential hypertension and without known clinical cardiovascular disease. Aortic stiffness was determined from carotid-femoral pulse wave velocity at baseline in 1045 hypertensives. The risk assessment of coronary heart disease was made by calculating the Framingham risk score according to the categories of gender, age, blood pressure, cholesterol, diabetes, and smoking. Mean age at entry was 51 years, and mean follow-up was 5.7 years. Coronary events (fatal and nonfatal myocardial infarction, coronary revascularization, and angina pectoris) and all cardiovascular events served as outcome variables in Cox proportional-hazard regression models. Fifty-three coronary events and 97 total cardiovascular events occurred. In univariate analysis, the relative risk of follow-up coronary event or any cardiovascular event increased with increasing level of pulse wave velocity; for 1 SD, ie, 3.5 m/s, relatives risks were 1.42 (95% confidence interval [CI], 1.10 to 1.82; P<0.01) and 1.41 (95% CI, 1.17 to 1.70; P<0.001), respectively. Framingham score significantly predicted the occurrence of coronary and all cardiovascular events in this population (P<0.01 and P<0.0001, respectively). In multivariate analysis, pulse wave velocity remained significantly associated with the occurrence of coronary event after adjustment either of Framingham score (for 3.5 m/s: relative risk, 1.34; 95% CI, 1.01 to 1.79; P=0.039) or classic risk factors (for 3.5 m/s: relative risk, 1.39; 95% CI, 1.08 to 1.79; P=0.01). Parallel results were observed for all cardiovascular events. This study provides the first direct evidence in a longitudinal study that aortic stiffness is an independent predictor of primary coronary events in patients with essential hypertension.

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PubMedDate not supplied

Pathophysiology of hypertension in the elderly.

Systolic hypertension is the most common type of hypertension in the elderly and a major modifiable cardiovascular risk factor. Systolic hypertension is associated with a wide pulse pressure resulting largely from excessive large artery stiffness. Arterial stiffness increases with age independently of mean blood pressure or the presence of other risk factors. In this review, the authors discuss the effects of age and blood pressure on arterial stiffness, the physiology of arterial compliance, and the anatomic changes of large arteries with aging. In most studies reported in the literature, elderly populations are relatively small. The role of both age and gender on arterial stiffness and wave reflection has been poorly investigated, particularly in subjects over 70 years. In this elderly population, further research is needed concerning the pathophysiology, epidemiology, and pharmacology of hypertension.

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