lacidipine and Atherosclerosis

Drugs currently known as calcium channel blockers (CCB) were initially called calcium antagonists because of their ability to inhibit calcium-evoked contractions in depolarized smooth muscles. Blocking the entry of calcium reduces the active tone of vascular smooth muscle and produces vasodilatation. This pharmacological property has been the basis for the use of CCBs in the management of hypertension and coronary heart disease. A major question is whether drugs reducing blood pressure have other effects that help prevent the main complications of hypertension, such as atherosclerosis, stroke, peripheral arterial disease, heart failure and end-state renal disease. Experimental studies that focus on this question are reviewed in the present paper.

Topics: Animals; Antioxidants; Atherosclerosis; Calcium Channel Blockers; Calcium Channels; Dihydropyridines; Humans; Hypertension; Oxidative Stress

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

Information on the features of long-term modifications of clinic and 24-h ambulatory blood pressure (ABP) by treatment is limited. The present study aimed to address this issue.. Ambulatory BP monitoring and clinic BP (CBP) measurements were performed at baseline and at yearly intervals over a 4-year follow-up period in 1523 hypertensives (56.1 +/- 7.6 years) randomized to treatment with lacidipine or atenolol in the European Lacidipine Study on Atherosclerosis (ELSA).. CBP was always greater than ABP, while reductions in all BP values (greater for CBP than for ABP) were on average maintained throughout 4 years, CBP changes showing limited relationship with ABP changes (r = 0.14-0.27). BP reductions by treatment during daytime and night-time were correlated (r = 0.63-0.73). BP normalization was achieved in a greater percentage of patients for CBP (41.7%) than for ABP (25.3%), with systolic BP control being always less common than diastolic BP control. BP normalization was more frequent at single yearly visits than throughout the 4 years. Twenty-four-hour BP variability was reduced by treatment over 4 years in absolute but not in normalized units.. The present study provides the best evidence available on long-term effect of antihypertensive treatment on both ABP and CBP. On average, ABP was sustainedly reduced by treatment throughout the follow-up period, but 24-h BP was more difficult to control than CBP. In several patients, ABP control was unstable between visits, the percentage of patients under control over 4 years being much less than that of those controlled at each year. Treatment induced a reduction in absolute but not in normalized BP variability estimates. This has clinical implications because of the prognostic importance of ABP mean values and variability.

Topics: Antihypertensive Agents; Atenolol; Atherosclerosis; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged

The European Lacidipine Study on Atherosclerosis (ELSA) randomized 2334 hypertensive patients to either the lipophilic calcium antagonist lacidipine or the beta-blocker atenolol for 4 years. About 35% of subjects in both groups received additional hydrochlorothiazide (12.5-25 mg/day). The patients were followed up for carotid intima-media thickness (IMT) changes for 3.7 years.. The present post-hoc analyses were aimed at: describing the prevalence of the metabolic syndrome (MS) at baseline; investigating the effect of long-term antihypertensive therapy (and separately of atenolol and lacidipine) on MS prevalence; exploring whether MS at baseline influenced changes in carotid IMT and incidence of cardiovascular events during treatment; and describing the relations between MS and new cases of diabetes developing during treatment.. At baseline 2034 patients had, in addition to blood pressure (BP), measurements of blood glucose, serum high-density lipoprotein (HDL)-cholesterol, triglycerides and body mass index (BMI > 28.8 for men and > 26.2 for women were taken to correspond to waist circumference > 102 and > 88 cm, respectively). These measurements were repeated after 4 years of treatment in 1444 patients. MS was defined according to Adults Treatment Panel III (ATP III).. A high proportion of ELSA patients (33.3%) had MS at baseline, with no difference between atenolol and lacidipine. Baseline IMT was slightly greater in MS patients, but only the difference in mean maximum IMT at common carotids and bifurcations (CBMmax) achieved significance (P = 0.0325). Progression of CBMmax was also slightly greater in MS patients (P = 0.0241), but significance was lost when adjusted for covariates. No significant difference was found in the incidence of new cardiovascular events between patients with and without MS. The incidence of new MS was 21.4%, and significantly greater in patients under atenolol (25.2%) than lacidipine (17.7%; P = 0.0045). New-onset diabetes occurred in 5.54% of ELSA patients, and was three times higher among patients with than those without MS (10.28 versus 3.43%, P > 0.0001).. Our analyses show a high prevalence of MS in ELSA hypertensives, a substantial incidence of new cases of MS and diabetes, the latter mostly among patients with MS. These analyses also show that in ELSA lacidipine was superior to atenolol, not only in showing a lower progression of carotid atherosclerosis, but also in causing a significantly lower incidence of new MS.

Topics: Aged; Antihypertensive Agents; Atenolol; Atherosclerosis; Calcium Channel Blockers; Carotid Arteries; Cohort Studies; Diabetes Complications; Dihydropyridines; Europe; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged

Calcium channel blockers slow the progression of atherosclerosis. The purpose of the present experiments was to examine the action of lacidipine in a condition that accelerates the development of atherosclerosis in order to test the hypothesis that the protective action of lacidipine in atherosclerosis is unrelated to the reduction of blood pressure. Male ApoE-deficient mice (6 weeks old) were exposed either to normal chow (ND) or to a Western-type diet (WD, adjusted calorie diet containing 42% from fat) for 8 weeks. Western-type diet induced a reduction of nitric oxide (NO)-mediated endothelium-dependent relaxation to acetylcholine (Max relaxation % = 55.8 +/- 2 for ND and 46.6 +/- 2 for WD, n = 8, p < 0.05). Dose-relaxation curves to S-nitroso-N-acetylpenicillamine (SNAP) NO donor were also significantly rightward-shifted (n = 7, ANOVA, p < 0.01) in WD compared with ND arteries. Chronic treatment of WD mice with lacidipine (1 and 3 mg/kg/day) increased significantly the acetylcholine-evoked relaxation (to 76.6 +/- 3.5%, n = 6, ANOVA, p < 0.001) and prevented the loss of responsiveness to SNAP in mice exposed to WD. Plasma renin activity and endothelin-1 plasma levels as well as thiobarbituric acid-reactive substance levels in kidneys were significantly lower in WD mice treated with lacidipine than in untreated ones. In mice exposed to WD lacidipine reduced extension of atherosclerotic lesions, renal injury and increase in blood pressure. Experimental data indicate that inhibition of Western-type diet-evoked alterations is related to both antioxidant and vasoactive properties of lacidipine.

Topics: Acetylcholine; Animals; Apolipoproteins E; Atherosclerosis; Calcium Channel Blockers; Cholesterol, HDL; Cholesterol, LDL; Diet; Dihydropyridines; Kidney Glomerulus; Male; Mice; Nitric Oxide; Penicillamine; Tunica Media; Vasoconstriction