[Resistant hypertension and carotid baroreceptors stimulation]. / HTA résistante et barostimulation carotidienne.

Resistant hypertension remains a frequent and difficult situation; its management has been recently clarified by guidelines from the French Society of Hypertension. Baroreceptor stimulation (BAROSTIM) is an emerging technique aimed at decreasing blood pressure in resistant hypertension. BAROSTIM interferes with baroreflex loop by stimulating baroreceptors and afferences of the baroreflex. There is only one randomized control trial with this technique which showed a modest but apparently durable blood pressure reduction. More evidences are required to refine the place of BAROSTIM, particularly with new devices. Together with renal denervation, BAROSTIM belongs to a new family of interventional techniques which should be considered as potential add-on therapies while optimal medical therapy remains the cornerstone of hypertension management.

Assessment of relationship on excess fluoride intake from drinking water and carotid atherosclerosis development in adults in fluoride endemic areas, China.

Cross-sectional analysis was conducted to access the relationships between developing carotid artery atherosclerosis through consuming high fluoride in drinking water and its possible mechanism, using the baseline data collected from 585 study subjects. In the cross sectional analysis, subjects were divided into four groups based on the concentrations of fluoride in their drinking water. The range of fluoride concentrations was: normal group (less than 1.20 mg/L), mild group (1.21-2.00 mg/L), moderate group (2.01-3.00 mg/L), and high concentration group (more than 3.01 mg/L). The prevalence rate of carotid artery atherosclerosis in the subjects in each group was found to be 16.13%, 27.22%, 27.10%, and 29.69%, respectively. Significant difference between the prevalence of carotid artery atherosclerosis in the mild, moderate and high fluoride exposure group and in the normal group was observed (P<0.05). In addition, it was found that elevated intercellular cell adhesion molecule-1 (ICAM-1) and reduced glutathione peroxidases (GPx) was associated with carotid artery atherosclerosis in fluoride endemic areas. The findings of the research study revealed a significant positive relationship between excess fluoride exposure from drinking water and prevalence of carotid artery atherosclerosis in adults living in fluoride endemic areas. The possible mechanism was the excess fluoride induced the decreasing level of GPx causing the systemic inflammation and endothelial activation by oxidative stress.

Thrombolytic effects of the snake venom disintegrin saxatilin determined by novel assessment methods: a FeCl3-induced thrombosis model in mice.

Saxatilin, a novel disintegrin purified and cloned from the venom of the Korean snake Gloydius saxatilis, strongly inhibits activation and aggregation of platelets. Glycoprotein (GP) IIb/IIIa receptor antagonists can resolve thrombus, so saxatilin might also have thrombolytic effects. We investigated the thrombolytic effects of saxatilin in mice using a ferric chloride-induced carotid arterial thrombosis model. Thrombotic occlusion and thrombus resolution were evaluated quantitatively by measuring blood flow in the carotid artery with an ultrasonic flow meter and calculating the degree of flow restoration on a minute-by-minute basis; results were confirmed by histological examination. Saxatilin dissolved thrombi in a dose-dependent manner. Saxatilin at 5 mg/kg restored blood flow to baseline levels. As saxatilin dose increased, time to recanalization decreased. A bolus injection of 10% of a complete dose with continuous infusion of the remaining dose for 60 minutes resulted in effective recanalization without reocclusion. The thrombolytic effect of saxatilin was also demonstrated in vitro using platelet aggregometry by administering saxatilin in preformed thrombi. Bleeding complications were observed in 2 of 71 mice that received saxatilin. Fibrin/fibrinogen zymography and platelet aggregometry studies indicated that saxatilin does not have fibrinolytic activity, but exerted its action on platelets. Integrin-binding assays showed that saxatilin inhibited multiple integrins, specifically α2bß3 (GP IIb/IIIa), α5ß1, αvß3, αvß1, and αvß5, which act on platelet adhesion/aggregation. Saxatilin inhibited multiple integrins by acting on platelets, and was safe and effective in resolving thrombi in mice.

MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course.

OBJECTIVES: The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI). BACKGROUND: Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo. METHODS: Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history <1 year, were randomly assigned to atorvastatin monotherapy or to atorvastatin-based combination therapies with appropriate placebos for 3 years. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for 3 years. All images were analyzed for quantification of wall area and plaque composition blinded to therapy, laboratory results, and clinical course. RESULTS: After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm(3) to 37.4 ± 69.5 mm(3) (p < 0.001) and %LRNC (LRNC area/wall area in the lipid-rich regions) from 14.2 ± 7.0% to 7.4 ± 8.2% (p < 0.001). The time course showed that %LRNC decreased by 3.2 (p < 0.001) in the first year, by 3.0 (p = 0.005) in the second year, and by 0.91 (p = 0.2) in the third year. Changes in LRNC volume followed the same pattern. Percent wall volume (100 × wall/outer wall, a ratio of volumes) in the lipid-rich regions significantly decreased from 52.3 ± 8.5% to 48.6 ± 9.7% (p = 0.002). Slices containing LRNC had significantly more percent wall volume reduction than those without (-4.7% vs. -1.4%, p = 0.02). CONCLUSIONS: Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273).

Telmisartan improves morphologic and functional changes in both left ventricular myocardium and carotid arterial wall in patients with hypertension: assessment by tissue Doppler imaging and carotid ultrasonography.

OBJECTIVE: The aim of the present study was to clarify the beneficial effects of telmisartan on the morphologic and functional changes in left ventricular (LV) myocardium and carotid arterial wall in patients with hypertension (HT) using tissue Doppler imaging and carotid ultrasonography. METHODS: Telmisartan (20-40 mg daily) was administered to 35 previously untreated patients with HT. Conventional and pulsed tissue Doppler echocardiography were performed after medication had been continued for 1-2 months with normal values for blood pressure (BP) (phase I) and for 12 months (phase II). Subclinical atherosclerosis also was determined by measuring the intima-media thickness (IMT) and stiffness ß of the left and right common carotid arteries using B- and M-mode ultrasonography. RESULTS: In the phase II, the LV mass index and isovolumic relaxation time were lower, the peak systolic and early diastolic mitral annular motion velocities were greater compared to the phase I. The stiffness ß and mean IMT were lower in the phase II than in the phase I. On multivariate regression analyses, age, BP, and LV diastolic variables emerged as stronger predictors of carotid arterial IMT and stiffness ß. CONCLUSIONS: The 1-year use of telmisartan improved LV hypertrophy, regional LV myocardial contraction and relaxation, and carotid atherosclerosis in patients with HT. Our results support cardio- and arterioprotective benefits from continuous long-term telmisartan monotherapy, and combined analysis of tissue Doppler imaging and carotid ultrasonography may be a useful tool for understanding ventriculoarterial coupling in patients with HT.

Effects of sources of variability on sample sizes required for RCTs, applied to trials of lipid-altering therapies on carotid artery intima-media thickness.

OBJECTIVE: Studies measuring progression of carotid artery intima-media thickness (cIMT) have been used to estimate the effect of lipid-modifying therapies cardiovascular event risk. The likelihood that future cIMT clinical trials will detect a true treatment effect is estimated by leveraging results from prior studies. The present analyses assess the impact of between- and within-study variability based on currently published data from prior clinical studies on the likelihood that ongoing or future cIMT trials will detect the true treatment effect of lipid-modifying therapies. METHODS: Published data from six contemporary cIMT studies (ASAP, ARBITER 2, RADIANCE 1, RADIANCE 2, ENHANCE, and METEOR) including data from a total of 3563 patients were examined. Bayesian and frequentist methods were used to assess the impact of between study variability on the likelihood of detecting true treatment effects on 1-year cIMT progression/regression and to provide a sample size estimate that would specifically compensate for the effect of between-study variability. RESULTS: In addition to the well-described within-study variability, there is considerable between-study variability associated with the measurement of annualized change in cIMT. Accounting for the additional between-study variability decreases the power for existing study designs. In order to account for the added between-study variability, it is likely that future cIMT studies would require a large increase in sample size in order to provide substantial probability (> or =90%) to have 90% power of detecting a true treatment effect.Limitation Analyses are based on study level data. Future meta-analyses incorporating patient-level data would be useful for confirmation. CONCLUSION: Due to substantial within- and between-study variability in the measure of 1-year change of cIMT, as well as uncertainty about progression rates in contemporary populations, future study designs evaluating the effect of new lipid-modifying therapies on atherosclerotic disease progression are likely to be challenged by large sample sizes in order to demonstrate a true treatment effect.

Functional assessment of vascular reactivity after chronic intermittent hypoxia in the rat.

We recently developed a model of chronic intermittent hypoxia (CIH) (FiO2 5%, 8 h/day, 35 days) in the rat that was associated with an increased infarction in isolated heart. The aim of the present study was to characterize its functional consequences on vasoreactivity. Aorta and carotid artery were studied using organ bath technique while mesenteric vascular bed was perfused. In the three vascular beds, relaxation to acetylcholine was similar in CIH and control normoxic (NX) rats. Contractions to noradrenaline and angiotensin II were similar between CIH and NX rats. In contrast, contraction to endothelin-1 was increased by 17% (P < 0.05) in carotid artery from CIH rats. Indomethacin pre-treatment reduced by 24% (P < 0.001) contraction to endothelin-1 in carotid artery from CIH rats only. These data suggested that 35-day CIH-exposure induced no change in endothelial function of aorta, carotid artery and mesenteric bed. In contrast, CIH-exposure induced an increased contractile response to endothelin-1 in carotid artery, presumably owing to the release of constrictor cyclooxygenase-derived products.

High resolution ultrasound assessment of the carotid artery: its relevance in postmenopausal women and the effects of tibolone on carotid artery ultrastructure.

OBJECTIVES: Hormone replacement therapy protects from cardiovascular disease at the menopause in part by reduction of menopausal pro-atherogenic serum lipid changes. Tibolone has beneficial effects on lipids, although serum high density lipoprotein levels decrease. This study aimed primarily to establish the effects of long-term administration of tibolone on a new surrogate marker for cardiovascular disease risk, the measurement of carotid artery intima-media thickness (CIMT) using high-resolution ultrasound. METHODS: Measurement of CIMT and assessment of carotid atherosclerotic plaques were undertaken in 31 women on tibolone and 30 voluntary controls from an ongoing open-label study of tibolone. RESULTS: The two groups were comparable, except for mean age and prevalence of current smokers. Repeatability of CIMT measurements was acceptable (CV, 10.0%). CIMT was significantly thicker in those with atherosclerotic plaques and increased systolic blood pressure. Prevalence of plaques was raised in those who had ever smoked, and those with elevated systolic blood pressure. There was no influence of tibolone on CIMT, whether plaques were present or not. CONCLUSIONS: This reliable technique demonstrates associations between CIMT and established risk factors. CIMT was significantly thicker in those with existing plaques. We did not demonstrate an effect of long-term tibolone use on either CIMT or prevalence of plaques.

Noninvasive assessment of regional arteriolar and arterial dilating properties of lisinopril in healthy volunteers.

The effects of single oral doses of lisinopril (5 and 20 mg) on systemic and regional hemodynamics were investigated noninvasively in a placebo-controlled, randomized, double-blind, cross-over study of 6 healthy male volunteers. Lisinopril induced a dose-dependent (significant after 20 mg) and long-lasting (< or = 8 h) decrease in mean arterial pressure (MAP, approximately 11% after 20 mg) that was related to a decrease in total peripheral resistance (TPR), because simultaneously heart rate (HR) and cardiac output (CO) were unchanged. Brachial artery flow (+42 and +47% after 5 and 20 mg, respectively) and diameter (+8 and +9%) increased significantly, whereas brachial vascular resistance (-31 and -38%) decreased significantly from 2 to 8 h after drug intake. Common carotid artery flow (+20 and +24%) also increased significantly, whereas corresponding resistance (-18 and -26%) decreased significantly during the same period. Finally, CO was significantly redistributed toward the brachial and, to a lesser extent, the carotid vascular beds after both doses of lisinopril. We conclude that in healthy subjects lisinopril, at non- or slightly hypotensive doses, dilates both arterioles and large arteries and that this vasodilation is not homogeneous, affecting preferentially the brachial rather than the carotid vascular bed.

Characterization of the responses of isolated rings of rabbit left carotid artery. A potential protocol for the assessment of pathologically induced functional changes.

Studies on such injury processes as atherosclerosis, angioplasty, and restenosis, have shown an impairment of relaxations mediated by endothelium-derived relaxing factor (EDRF). Increasingly, the rabbit carotid artery is being used as the vessel of choice in such studies, but a definite protocol for the assessment of endothelial dysfunction or denudation has not been developed. Using isolated carotid artery rings, we have obtained reproducible dose-response curves in endothelially intact and denuded vessels from normally fed rabbits to a variety of vasoconstrictors and endothelium-dependent and -independent vasodilators. Endothelium-dependent vasodilators (acetylcholine (1 x 10(-8)-1 x 10(-6) M), carbachol (1 x 10(-8)-5 x 10(-6) M), substance P (0.01-100 nM), and A23187 (1 x 10(-8)-1 x 10(-7) M) relaxed the arteries in a concentration-dependent manner but produced no relaxation in denuded vessels. Endothelium-independent nitric oxide (NO) donors [Sin-1 (1 x 10(-8)-1 x 10(-6) M)] and sodium nitroprusside (1 x 10(-8)-1 x 10(-6) M)) relaxed both intact and denuded vessels to a similar degree (slight augmentation of the relaxation induced in denuded vessels was not significant), demonstrating that denuded vessels did not have an impaired reactivity to NO. Concentration response curves to the vasoconstrictors [5-HT (1 x 10(-7)-1 x 10(-4) M) and KCl (15-60 mM)] were produced in intact vessels and it was shown that similar contraction was produced by 1 x 10(-6) M 5-HT in intact and denuded vessels. This indicated that the vessels retained contractile ability following denudation.(ABSTRACT TRUNCATED AT 250 WORDS)