Showing papers by "Stéphane Laurent published in 2004"

Increased Carotid Wall Stress in Vascular Ehlers-Danlos Syndrome

Abstract: Background— Vascular Ehlers-Danlos syndrome (vEDS), also known as EDS type IV, an inherited disorder of connective tissue, results from mutations in the gene encoding type III procollagen (COL3A1)....

Increased stiffness of the carotid wall material in patients with spontaneous cervical artery dissection

Abstract: Background and Purpose— The cause of spontaneous cervical artery dissection (sCAD) is largely unknown. An underlying connective tissue disorder has often been postulated, but arterial mechanical properties have rarely been studied. The study aim was to determine the elastic properties of a cervical artery, the common carotid artery, and a distal muscular artery, the radial artery in sCAD patients. Methods— We studied 32 patients with previous sCAD (median delay: 2.2 years) and 32 control subjects with similar age and blood pressure. Internal diameter, intima-media thickness, distensibility, and Young’s elastic modulus were determined at the site of the right and left common carotid arteries and the radial artery using noninvasive high-resolution echotracking systems. Results— In patients with previous sCAD, cross-sectional distensibility and compliance of the affected carotid artery did not differ from those of the contralateral carotid artery. Young’s elastic modulus (ie, the stiffness of the wall materi...

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

Abstract: BackgroundA 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

Guidelines from the British Hypertension Society.

Abstract: Hypertension represents a major public health concern. It affects about a billion people worldwide and is the most common treatable risk factor for cardiovascular disease in patients aged over 50. In the United Kingdom, the prevalence of hypertension (blood pressure more than 140/90 mm Hg) has been estimated to be 42% in people aged 35 to 64.1 Large benefits, in terms of avoided cardiovascular disease, are expected from the treatment of hypertension. However, these benefits are low because the control of hypertension remains poor in European countries—particularly in the United Kingdom, where it is controlled in only 10% of the hypertensive population.2 These past years, a huge quantity of novel data has been published on the prominent role of lowering blood pressure in the reduction of cardiovascular disease and on the safety and effectiveness of antihypertensive drugs. Two guidelines for management of hypertension, updating previous ones, were published in 2003.3,4 They originate from the European Society of Hypertension/European Society of Cardiology5 and the US Joint National Committee.6 Is it worth having a third one, written by the British Hypertension Society?7 Although the major features of most of these recommendations are similar, they differ in some aspects; doctors may consider these guidelines as matters for specialists and may exaggerate the difficulty of treating hypertension. Thus we run the risk of dilution of the main message, which is to simplify the therapeutic approach, at a time where all efforts are needed to fight against the under diagnosis and under treatment of hypertension. However, tailoring guidelines for the United Kingdom has two advantages: these recommendations implement previous guidelines which doctors are familiar with,8 and they are adapted to the NHS. The British guidelines, which are published as a summary in this issue (p 634), simplify the therapeutic approach by selecting a small number of evidence based key actions.7 Several boxes are added to give immediate answers to some key questions, for instance concerning the treatment target for antihypertensive drug therapy, or the contraindications for the major classes of antihypertensive drugs. The strength of these guidelines is to delineate clearly the main objectives of the primary care physician, and the means for reaching these objectives. For instance, the choice of initial treatment has been facilitated by recent meta-analyses showing that overall most classes of drugs are similarly safe and effective. These include the diuretics and β blockers (older drugs) and calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers (newer drugs).9 The British guidelines remind us that “the main determinant of benefit from blood pressure lowering drugs is the achieved blood pressure, rather than the choice of therapy.” In other words, the lower the pressure the better. Worldwide, a common reason for poor control of blood pressure is that most doctors keep using monotherapy in patients who obviously need combination therapy to normalise blood pressure. The British guidelines insist on at least two blood pressure lowering drugs in most patients. A simple treatment algorithm, named AB/CD, is now formally incorporated into the guidelines and underscores the need for two or three drugs for most patients.10 Particularly, it states that drugs that inhibit the renin-angiotensin system—angiotensin converting enzyme inhibitors and angiotensin II receptor blockers (A) or β blockers (B)—should be logically combined with drugs which do not inhibit it—calcium channel blockers (C) or diuretics (D).11 Although this therapeutic approach has yet to be validated by controlled trials, it illustrates the pharmacological synergy between drugs. By recommending the AB/CD algorithm, the British guidelines are more prescriptive than the European guidelines, which maintained α blockers as first line drug treatment and offered a larger possibility of drug combinations. The British guidelines also differ from the US guidelines, which positioned thiazide-type diuretics in the centre of treatment strategy after the ALLHAT trial showed that a therapeutic strategy based on a thiazide-type diuretic was superior to strategies based on a calcium channel antagonist or an angiotensin converting enzyme inhibitor in preventing some major forms of cerebrovascular disease. These different therapeutic strategies should be compared for their effectiveness in lowering blood pressure and cerebrovascular disease. “The lower the pressure the better” is particularly true for patients at high cardiovascular risk. The British guidelines provide simple means, like European guidelines and to a larger extent than US guidelines, for identifying hypertensive patients at high cardiovascular risk—diabetes, complications of hypertension, target organ damage, or a 10 year cerebrovascular disease risk of 20% or more. (A risk scoring system to detect these patients more precisely, jointly established by the British societies and adapted from epidemiological data recorded in the United Kingdom, is available in the full version of the British Hypertension Society's guidelines or on the society's website (www.bhsoc.org).12) The theoretical benefit in reducing cerebrovascular disease is largest in this high risk population. Unfortunately, this is precisely the population in which the rate of control of hypertension is one of the lowest. In any case, adherence of primary care physicians to the British guidelines is key to successfully treating their individual patients, thus improving the rate of control of hypertension and reducing cardiovascular events.

Contrasting circadian rhythms of blood pressure among inbred rat strains: recognition of dipper and non-dipper patterns.

Abstract: ObjectiveThe non-dipper pattern, i.e. the lack of nocturnal blood pressure (BP) fall, carries a high risk of cardiovascular complications, both in hypertensive and normotensive subjects. Without genetic engineering, experimental demonstration of the non-dipper phenomenon is lacking. The purpose of t

Rationale, design and methods of the CASHMERE study

Abstract: 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.

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

Abstract: 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.

Remodelage des grosses et petites artères dans l‘hypertension artérielle

Abstract: Le remodelage vasculaire correspond a toute modification de structure et de fonction arterielle au cours de processus physiologiques et pathologiques. Les modifications adaptatives sur le court terme peuvent s‘accompagner de consequences pathologiques sur le long terme. Au cours de l‘hypertension arterielle, les consequences sont differentes selon que l‘on s‘interesse aux petites arteres de resistances ou aux arteres de conduction. Les arteres de resistances subissent trois types de phenomenes : 1) un remodelage concentrique dit eutrophique, c‘est‐a‐dire une reorganisation de la meme quantite de tissus autour d‘un diametre plus petit ; 2) une rarefaction du lit arteriolaire, c‘est‐a‐dire une densite arteriolaire diminuee par unite ponderale de tissu perfuse ; 3) une atteinte precoce de la fonction endotheliale, avec diminution de la biodisponibilite du monoxyde d‘azote (NO). La consequence globale est une augmentation des resistances peripheriques, une alteration des capacites de vasodilatation et une ischemie tissulaire en condition critique de perfusion. Les methodes d‘exploration de ces differentes composantes sont insuffisantes pour les proposer en routine. L‘atteinte des grosses arteres est dominee par l‘hypertrophie excentrique, l‘augmentation de rigidite et la perte de compliance. Cette augmentation de rigidite depend du territoire arteriel. Elle est importante pour l‘aorte, moderee pour les arteres elastiques, paradoxalement diminuee pour les arteres musculaires, refletant les effets cumules de l‘hypertrophie musculaire lisse vasculaire (predominant en peripherie), et les modifications de matrice extracellulaire (predominant pour les arteres elastiques). La valeur pronostique pejorative de l‘hypertrophie et de la rigidification sont maintenant bien etablies. Ces deux lesions constituent a proprement parler l‘atteinte de l‘artere en tant qu‘organe cible.

Comparison of angiotensin ii-induced blood pressure and structural changes in fischer 344 and wistar kyoto rats

Abstract: 1. The purpose of the present study was to evaluate the blood pressure (BP) response, the BP and heart rate (HR) components of the startle reaction and the structure of the carotid artery and the aorta during chronic infusion of angiotensin (Ang) II in Fischer 344 (F344) compared with Wistar Kyoto (WKY) rats, two in-bred normotensive contrasted strains. 2. Osmotic mini-pumps filled with saline vehicle or AngII (120 ng/kg per min) were implanted subcutaneously in 8-week-old normotensive rats and infused for 4 weeks in F344 rats (saline, n = 10; AngII, n = 10) and WKY rats (saline, n = 10; AngII, n = 9). Basal BP, HR and the responses to an acoustic startle stimulus (duration 0.7 s, 115 dB) were recorded in conscious rats. The structure of the carotid artery and aorta was determined in 4% formaldehyde-fixed arteries. 3. Compared with WKY rats, vehicle-treated F344 rats had lower bodyweight (BW; 266 +/- 7 vs 299 +/- 9 g; P < 0.05) and heart weight (0.80 +/- 0.02 vs 0.98 +/- 0.04 g; P < 0.05) and higher aortic systolic BP (SBP; 131 +/- 1 vs 123 +/- 5 mmHg; P < 0.001) and diastolic BP (98 +/- 3 vs 89 +/- 2 mmHg; P < 0.001). In F344 rats, compared with the WKY rats, the wall thickness/BW ratio was increased in the carotid artery (156 +/- 9 vs 131 +/- 6 nm/g; P < 0.05) and abdominal aorta (264 +/- 13 vs 217 +/- 12 nm/g; P < 0.05) and decreased in the thoracic aorta (246 +/- 13 vs 275 +/- 8 nm/g; P < 0.05). There was no difference in elastin and collagen density. Angiotensin II differentially enhanced BP in both strains: (SBP: 163 +/- 5 and 132 +/- 4 mmHg in F344 and WKY rats, respectively; P(strain x treatment) < 0.05). Circumferential wall stress was increased in the aorta of F344 rats compared with WKY rats (1176 +/- 39 vs 956 +/- 12 kPa (P < 0.001) and 1107 +/- 42 vs 813 +/- 12 kPa (P < 0.001) in thoracic and abdominal aortas, respectively). The startle response was amplified in F344 rats, with enhanced increases in SBP and pulse pressure (PP) and bradycardia compared with responses of WKY rats (+44 +/- 9 mmHg, +10 +/- 2 mmHg and -40 +/- 17 b.p.m., respectively, in F344 rats vs+28 +/- 4 mmHg, + 4 +/- 2 mmHg and -19 +/- 10 b.p.m. in WKY rats, respectively; P(strain) < 0.05 for BP and PP). The startle response was not affected by AngII. 4. These results indicate a higher BP producing an increase in wall thickness in F344 rats compared with WKY rats. We propose that an increase in sympathetic nervous activity causes these haemodynamic differences, as suggested by the excessive increase in BP during an acoustic startle stimulus. Angiotensin II increased BP in F344 rats, but did not exaggerate the increase in BP during the startle reaction.

Une nouvelle stratégie dans le traitement de l’hypertension artérielle et de ses lésions sur les organes cibles

Abstract: Resume Preserver la perfusion tissulaire des organes essentiels devrait etre, en definitive, le veritable but de tout antihypertenseur. Des decouvertes majeures permettent aujourd’hui de mieux comprendre pourquoi tous les organes essentiels souffrent tres precocement, lors de l’hypertension, d’une ischemie tissulaire et pourquoi, face a ces alterations, les traitements antihypertenseurs obtiennent des benefices si inegaux. La maladie hypertensive entraine chez tous les hypertendus, des alterations vasculaires avec, au niveau de la microcirculation, une rarefaction arteriolocapillaire. Ces decouvertes ont des consequences capitales puisqu’il est etabli que la microcirculation regule non seulement la majorite des resistances peripheriques, mais surtout conditionne la qualite de perfusion de tous les organes essentiels. Il est essentiel d’evaluer les differentes strategies antihypertensives non seulement sur un plan tensionnel mais aussi sur leur impact vasculaire et leur capacite a preserver le reseau microvasculaire des atteintes liees a l’hypertension.