dihydropyridines and Carotid-Artery-Diseases

Whether increased serum uric acid (SUA) favours resistance to antihypertensive drugs is not clear.. The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind, multicenter trial comparing the effects of a 4-year treatment with either lacidipine or atenolol on progression of carotid atherosclerosis in patients with moderate hypertension. SUA was assessed at randomization and at the study end, office blood pressure (BP) was measured at each titration visit and every 6 months thereafter, ambulatory BP was measured at randomization and every year thereafter.. No difference was found in office and ambulatory BP reduction achieved after 1 and 4 years of treatment in baseline SUA tertiles. This was the case for both treatments. The percentage of patients with controlled office BP (<140/90 mmHg) after 1 year (36.5, 34.2 and 33.8%, P = 0.56) and 4 years (39.9, 39.4 and 38%, P = 0.82) was not different in SUA tertiles. Similar results were obtained basing the analysis on the control of ambulatory BP (<130/80 mmHg) or when data were analyzed taking into account SUA extreme values (≥7 and <3.5 mg/dl). The average and percentage changes of SUA (baseline-study end) were not different between patients who achieved or did not achieve office BP control (5.31 ± 1.26 vs. 5.4 ± 1.29 mg/dl, P = 0.22 e 0.13 ± 0.33 vs. 0.13 ± 0.68, P = 0.87, respectively). This was the case also for control of ambulatory BP.. In the ELSA study, SUA levels do not affect the responsiveness to antihypertensive treatment.

Topics: Antihypertensive Agents; Atenolol; Atherosclerosis; Blood Pressure; Carotid Artery Diseases; Dihydropyridines; Disease Progression; Double-Blind Method; Drug Resistance; Female; Humans; Hypertension; Male; Middle Aged; Uric Acid

In high-cardiovascular-risk treated hypertensive patients, the incidence of cardiovascular events has been reported to relate to visit-to-visit blood pressure (BP) variability. We investigated whether visit-to-visit BP variability is prognostically important in treated mildly to moderately hypertensive patients in whom treatment aims at avoiding events but also at preventing or delaying progression of organ damage.. We analyzed the pooled data from the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind 4-year trial of the effect of lacidipine or atenolol on echographic carotid intima-media thickness. Visit-to-visit BP variability was assessed by the coefficient of variation or the SD of the mean on-treatment systolic BP (SBP) obtained at 6- (clinic BP) and 12- (24 hours BP) month intervals, respectively (1521 and 1264 patients, respectively). In a multivariable linear regression model, mean on-treatment clinic or 24-hour SBP, but not SBP coefficient of variation or SD, was associated with end-of-treatment carotid intima-media thickness. Intima-media thickness increased progressively from the lowest to highest quartile of mean on-treatment clinic or 24-hour SBP (adjusted P for trend=0.046 and 0.048) but not along similar quartiles of SBP coefficient of variation or SD. In a multivariable logistic regression model, mean BP, but not variability, was associated with cardiovascular outcomes.. In mildly to moderately hypertensive patients, carotid intima-media thickness and cardiovascular outcomes were related to the mean clinic or ambulatory SBP achieved by treatment but not to on-treatment visit-to-visit clinic or 24-hour BP variability. Thus, when BP is modestly elevated, inconsistency of BP control between visits plays a less important prognostic role than long-term average BP levels.

Topics: Adrenergic Antagonists; Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Intima-Media Thickness; Circadian Rhythm; Dihydropyridines; Double-Blind Method; Europe; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Office Visits; Prognosis; Prospective Studies; Treatment Outcome

In the European Lacidipine Study on Atherosclerosis (ELSA), against a similar antihypertensive effect, a significantly greater effect of lacidipine was found on carotid intima-media thickness (IMT) progression, indicating a specific anti-atherosclerotic effect of lacidipine. However, not only the extent but also the composition of an atherosclerotic plaque is a determinant of subsequent events.. Among the 2334 patients enrolled in ELSA, 420 with 4-year treatment were chosen, videodensitometric analysis of their ultrasound carotid scan was performed and the maximum wall lesion (Tmax) was classified as lipidic, fibrolipidic and fibrotic by means of software previously validated against histology. Of the 420 patients, 244 had scans suitable for videodensitometry.. Excellent reproducibility of videodensitometry analysis was found using the Bland-Altman and other methods. At baseline, ELSA hypertensive patients had predominantly fibrolipidic walls (70%), with an echoreflectivity indicating a mean collagen content of 25%. After 4 years of antihypertensive treatment, little change in the frequency distribution of carotid lesions (fibrolipidic 73%) was found, with no significant differences between patients randomized to lacidipine or atenolol.. Our study provides previously unavailable information that carotid wall composition changes to an extremely small extent during 4-year effective blood pressure lowering. With lacidipine, stable composition is associated with a lower IMT progression than with atenolol.

Topics: Adult; Aged; Antihypertensive Agents; Atenolol; Carotid Arteries; Carotid Artery Diseases; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Reproducibility of Results; Tunica Intima; Tunica Media; Ultrasonography

In ELSA, a randomized, double-blind trial in 2334 hypertensives, 4-year antihypertensive treatment with lacidipine slowed down progression of carotid atherosclerosis significantly more than atenolol treatment. To avoid bias, the primary outcome was measured blindly at study-end on a randomized sequence of scans, but measurements were limited to the four far walls of common carotids and bifurcations (CBMmax) and to one of each couple of duplicate scans recorded yearly.. Secondary outcomes included measurements made on all duplicate scans of both near and far walls, not only of common carotids and bifurcations, but also of internal carotids (12 walls). These measurements were made blindly during the 4-year study, shortly after recording. To avoid possible readers' drift or bias, 250 duplicate baseline scans were re-read at yearly intervals (longitudinal on-line quality control) and a correction factor calculated.. Measurements during the 4-year study showed a trend toward decreased values, with the lacidipine effect significantly greater than the atenolol one. A trend toward lower values was also observed in the longitudinal quality control of baseline scans. After applying a correction factor calculated from this longitudinal control, all measurements no longer decreased with time, but significantly increased, with progression being significantly smaller in lacidipine than in atenolol patients. Corrected values were quite similar to those calculated on measurements carried out at study-end.. The relative benefit of lacidipine over atenolol could be measured precisely by reading scans either during the study or at study-end. However, absolute treatment-related changes (progression versus regression) cannot safely be judged by readings made during a long-term study, unless a longitudinal quality control of readings is performed.

Topics: Aged; Antihypertensive Agents; Atenolol; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, Internal; Dihydropyridines; Disease Progression; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Time Factors; Tunica Intima; Tunica Media; Ultrasonography

Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering.. The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in far walls of common carotids and bifurcations (CBM(max)). This index has been shown by epidemiological studies to be predictive of cardiovascular events. A significant (P<0.0001) effect of lacidipine was found compared with atenolol, with a treatment difference in 4-year CBM(max) progression of -0.0227 mm (intention-to-treat population) and -0.0281 mm (completers). The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients (completers, 40% reduction; P=0.0073). Patients with plaque progression were significantly less common, and patients with plaque regression were significantly more common in the lacidipine group. Clinic blood pressure reductions were identical with both treatments, but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg). No significant difference between treatments was found in any cardiovascular events, although the relative risk for stroke, major cardiovascular events, and mortality showed a trend favoring lacidipine.. The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller ambulatory blood pressure reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Carotid Arteries; Carotid Artery Diseases; Dihydropyridines; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Time; Treatment Outcome; Tunica Intima; Tunica Media; Ultrasonography

In the ELSA trial, the effects of lacidipine-based treatment and beta-blocker (atenolol)-based treatment on the development and progression of carotid wall alterations are assessed in hypertensive patients. The primary endpoint of this study is the rate of change in the intima-media thickness of the carotid artery wall, measured with B-mode ultrasound. About 2300 hypertensive patients have been recruited and randomized to either of the antihypertensive agents. Baseline data for 1965 patients are available, showing a high prevalence of carotid wall lesions: about 82% of the subjects have an intima-media thickness > or = 1.3 mm, defined as plaque in the ELSA protocol; 16% of the subjects have intima-media thickening (> or = 1.0 mm, < 1.3 mm) and only about 1% have normal carotid artery walls. Analysis of demographic data and risk factor prevalence in ELSA patients, and comparison of these preliminary observations with data from other intervention or observational studies indicate that high blood pressure is a very important risk factor for carotid atherosclerosis.

Topics: Antihypertensive Agents; Arteriosclerosis; Carotid Artery Diseases; Dihydropyridines; Europe; Female; Humans; Hypertension; Male; Middle Aged; Prevalence

Up to the present the relationship between arterial hypertension or its treatment and cardiovascular complications has been evaluated in terms of the incidence of events, such as fatal and nonfatal myocardial infarction or stroke and cardiac deaths. However, cardiovascular events are not the direct consequence of blood pressure elevation, which, on the contrary, is responsible for atherosclerotic disease. Quantitative ultrasonography is a sensitive, specific and reproducible technique which, in comparison to arteriography, is non invasive and less expensive. The availability of this technique has allowed us to do some studies, one just published, another in the elaboration phase and others ongoing, aimed at evaluating the effects of antihypertensive agents on carotid changes in hypertensive patients. The European Lacidipine Study on Atherosclerosis (ELSA) compares the effects of lacidipine, a calcium-antagonist and of atenolol, a beta-blocker, on blood pressure, on carotid vessel modifications, and on the incidence of cardiovascular events in patients with mild to moderate hypertension with a 4-year follow-up period. Preliminary results of the study, which were concerned with the demographic characteristics of the first 1000 randomized patients enrolled, indicate that 84% of the patients had a carotid plaque, 15% had thickening of the intima-media, and 1% had a normal vessel. These results are both surprising and significant in that they admonish the physician not to neglect patients with mild to moderate hypertension even when they have neither complications nor other risk factors.

Topics: Aged; Antihypertensive Agents; Arteriosclerosis; Atenolol; Calcium Channel Blockers; Carotid Artery Diseases; Delayed-Action Preparations; Dihydropyridines; Double-Blind Method; Europe; Humans; Hypertension; Middle Aged

Although several antihypertensive agents reduced the carotid intima-media thickness (IMT), it remains unclear whether those agents affect the interadventitial diameter (IAD). We aimed to examine whether cilnidipine, an L/N-type calcium channel blocker, reduced the common carotid IMT or IAD in post-stroke hypertensive patients.. The common carotid IMT and IAD were measured at the start of cilnidipine treatment and 12 months from that. The changes in the mean max-IMT or IAD between baseline and the 12-month follow-up were evaluated and compared between the thick group (max-IMT ≥1.1 mm) and the normal group (max-IMT ＜1.1 mm).. A total of 603 post-stroke hypertensive subjects (mean age=69.3 yr, 378 males) were included in the analysis. At baseline, IAD was increased stepwise according to the value of max-IMT (p for trend ＜0.001). Among them, 326 subjects were followed up for 12 months. The mean max-IMT from baseline to 12 months did not change in the normal group (－0.01 mm, 95% confidence interval [CI] －0.03 to 0.01, n=170), whereas a significant reduction was observed in the thick group (－0.09 mm, 95% CI －0.13 to －0.05, n=156). The mean IAD was significantly reduced during the study period in the normal group (－0.14 mm, 95% CI －0.22 to －0.05) as well as in the thick group (－0.12 mm, 95% CI －0.21 to －0.03).. Cilnidipine promoted the regression of common carotid IMT in post-stroke hypertensive patients, especially in the thick group. Cilnidipine also reduced the IAD in both normal and thick groups.

Topics: Aged; Antihypertensive Agents; Calcium Channel Blockers; Calcium Channels, L-Type; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Dihydropyridines; Female; Follow-Up Studies; Humans; Hypertension; Male; Prognosis; Stroke

Topics: Blood Pressure; Cardiovascular Diseases; Carotid Artery Diseases; Circadian Rhythm; Dihydropyridines; Female; Humans; Hypertension; Male; Office Visits

Aim of the study was to evaluate the influence of the dihydropyridine derivative BW 9798 on intimal hyperplasia in a carotid artery injury model of New Zealand White rabbits on a high cholesterol diet.. In carotid arteries of 50 New Zealand White rabbits atherosclerotic lesions were induced by cholesterol diet and electrostimulation of the artery. In 40 animals the resulting primary lesion was subjected to balloon angioplasty (BA). Three days prior to BA animals received BW 9798 or placebo per os until sacrifice three days or 28 days after BA.. BW 9798 lead to increased cross sectional area by 128.3% and an increased luminal area by 157% after 28 days after BA compared with placebo. However the degree of stenosis did not significantly decrease. The cell count of the different layers of the arteries decreased by 64.5% in the intima and by 62.6% compared with placebo treated animals after BA. Additionally the number of smooth muscle cell (SMC) layers in the neointima was significantly lower in BW 9798 treated animals than in placebo animals (8±3 vs 14±9, p<0.05) although the proliferation was not changed by BW 9798 treatment 3 days after BA.. BW 9798 leads to significant changes in vessel wall geometry although the influence on vascular remodeling of this compound is unclear. It can be speculated that the compound affects the homeostasis of extracellular matrix, invasion of inflammatory cells into the vessel wall and the expression of cytokines. However, further investigation needs to clarify the role of BW 9798 on remodelling after BA.

Topics: Angioplasty, Balloon; Animals; Calcium Channel Blockers; Carotid Arteries; Carotid Artery Diseases; Carotid Artery Injuries; Cell Proliferation; Cholesterol, Dietary; Constriction, Pathologic; Dihydropyridines; Hyperplasia; Neointima; Rabbits; Tunica Intima

Effects of NB-818, a new Ca2+ entry blocker, on a transient cerebral ischemic model in Mongolian gerbils were examined. Following bilateral common carotid arteries occlusion of 20 min duration, all the control animals died within 24 hr after reperfusion. The administration of NB-818 at 0.1 mg/kg, i.p., 30 min after reperfusion significantly reduced the mortality rate to 65.0% (P less than 0.01); and 0.01 mg/kg, i.p., had a tendency to reduce the mortality rate. In the nimodipine-treated groups, a similar effects in the ischemic model. Furthermore, the administration of NB-818 at 0.1 mg/kg, i.p., 15 min before occlusion also had a tendency to reduce the mortality rate. On the incidences of seizures induced by transient cerebral ischemia, there were no significant differences between each of the drug-treated groups and the control group. In NB-818 and nimodipine-treated groups, the morbidity scores NB-818 and nimodipine in this severe cerebral ischemic model have advantages over those of nicardipine and flunarizine. Thus, these results suggest that NB-818 may be useful in the treatment of ischemic cerebral damage.

Topics: Animals; Arterial Occlusive Diseases; Calcium Channel Blockers; Carotid Artery Diseases; Dihydropyridines; Female; Flunarizine; Gerbillinae; Male; Nicardipine; Nimodipine