Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).
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PMID:Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR. 760 94

Membrane-active drugs can be characterized by direct measurements of their membrane partition coefficients, washout rates from membranes, and washin rates into membranes. There appears to be a correlation between the duration of action of such membrane-active drugs and the membrane partition coefficient in conjunction with the washout rate. Lacidipine has a high membrane partition coefficient compared to other 1,4-dihydropyridine calcium-channel antagonists and a slow washout rate from membranes. Clinically, it also exhibits an extended duration of action. This control at the membrane molecular level may provide an optimal pharmacokinetic profile for lacidipine in the treatment of hypertension. In addition, these same properties may be important for lacidipine as an antiproliferative agent in the treatment of atherosclerosis.
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PMID:The molecular basis for lacidipine's unique pharmacokinetics: optimal hydrophobicity results in membrane interactions that may facilitate the treatment of atherosclerosis. 760 1

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.
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PMID:[The preliminary clinical evidence from the ELSA study. The European Lacidipine Study on Atherosclerosis]. 856 72

The European Lacidipine Study on Atherosclerosis (ELSA) has been designed to compare the effects of two antihypertensive agents, the calcium antagonist lacidipine and the beta-blocker atenolol, on the development of atherosclerosis in hypertensive patients stratified according to the presence of carotid plaques, or the presence or absence of carotid artery intima-media thickening. ELSA is a multinational, multicenter, randomized, double-blind, parallel group study that is to be conducted over a 5-year period. Recruitment and treatment will take place at 23 referral centers in seven countries. A total cohort of 3,660 patients, aged between 45 and 75 years, with diastolic blood pressure 95-115 mm Hg and systolic blood pressure < or = 210 mm Hg at enrollment, will be stratified into three groups according to a B-mode ultrasound analysis of the carotid wall morphology. After a 1-month placebo run-in period, patients will be randomized to receive either lacidipine (4-6 mg once daily) or atenolol (50-100 mg once daily). Nonresponders will be treated with hydrochlorothiazide (12.5 mg, eventually titrated to 25 mg if required), on an open basis. During the course of the study, patients will be monitored by carotid ultrasound assessment and ambulatory blood pressure monitoring. The results of this study should further understanding of the pathobiology of atherosclerosis, and its development and prevention.
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PMID:Potential modification of plaque behavior through the European lacidipine study on atherosclerosis. 885 39

The development of atherosclerosis is clearly linked to the level of blood pressure. This is illustrated by the difference of atheroma formation in arteries as compared to veins, the development of atherosclerosis in veins transplanted to the arterial circulation or the finding of atherosclerosis also in the pulmonary circulation as an effect of pulmonary hypertension. Several experimental studies have also illuminated the strong link between high blood pressure and the development of atherosclerosis. From a therapeutic point of view it is worth noting that the lowering of blood pressure per se has a positive effect on the development of atherosclerosis. In particular, calcium antagonists have been shown, in numerous experimental studies, to have an antiatherosclerotic effect. The positive results in animal studies led to studies in man, the first of which was the MIDAS Study. The Multicentre Isradipine Diuretic Atherosclerosis (MIDAS) Study was a comparison between the dihydropyridine-derived calcium antagonist isradipine and hydrochlorothiazide in 883 hypertensive patients. B-mode ultrasonography of the carotid artery was used in order to evaluate changes in wall thickness and the development of atherosclerotic plaques during a 3-year period. The final publication has yet to appear in a medical journal. However, the study and its main findings have been presented at several international scientific meetings. In brief, isradipine was significantly more effective than hydrochlorothiazide in preventing an increase in intima-media thickness at several points of measurement in the carotid artery in spite of the fact that systolic blood pressure was not lowered as effectively by isradipine as by the diuretic therapy. There are numerous lessons to be learnt from MIDAS for future studies of this kind. A good example of this is the European Lacidipine Study of Atherosclerosis (ELSA) which is currently in progress in several European countries. By careful analysis of MIDAS an improved study design has been created, which should result in a definitive and irrefutable answer to the issue of the clinical importance of calcium antagonist treatment in the prevention of atherosclerosis.
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PMID:How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study. 897 77

The European Lacidipine Study on Atherosclerosis (ELSA) is a multinational interventional clinical trial aimed at determining the antiatherosclerotic effects of Lacidipine, a calcium antagonist, when compared to atenolol, a beta-blocker, on the carotid arteries of 2300 cardiovascular asymptomatic patients with moderately high blood pressure. Quantitative B-mode ultrasound imaging is being used to measure the intima-media thickness of a standardized section of the carotid arteries including the distal common, bifurcation, and proximal internal carotids. Prospective investigations of large samples of population using ultrasonographic endpoints rely heavily on the precision and reproducibility of the method. Therefore, specific quality control protocols are required to determine and monitor cross-sectional and longitudinal stability of the measurement reproducibility. In ELSA, the ultrasound methodology was specifically designed to include a set of procedures to quality control the critical components of measurement variation including instrumentation, and ultrasound operators, i.e. sonographers and readers. The ELSA clinical trial will provide the largest set of prospective quality control data on the use of quantitative B-mode ultrasound imaging.
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PMID:Ultrasound protocol and quality control procedures in the European Lacidipine Study on Atherosclerosis (ELSA). 897 78

An increasing amount of data suggests that systolic blood pressure (SBP) and pulse pressure (PP) may more closely relate to and thus favour the atherogenic process than does diastolic blood pressure (DBP). The baseline data from the ongoing European Lacidipine Study on Atherosclerosis (ELSA) recently indicated that carotid artery atherosclerosis in normocholesterolaemic patients with mild or moderate essential hypertension is more closely related to SBP and more so PP than to DBP and lipid variables. Other new data point to the effects of hypertension on arterial compliance, as well as the effects of 24-h blood pressure variability on arterial compliance and distensibility. When viewed in their entirety, these data present a compelling case for the closer monitoring of SBP and PP with respect to arterial compliance, and the need for aggressive blood pressure treatment to control and perhaps reverse the underlying pathological changes in arterial structure and function in hypertensive patients.
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PMID:Systolic blood pressure and pulse pressure: role of 24-h mean values and variability in the determination of organ damage. 1070 28

Lacidipine, a third generation dihydropyridine calcium antagonist, has demonstrated pronounced anti-atherosclerotic activity in preclinical studies. The drug can act at several stages within the atherosclerotic process, utilising its antihypertensive and antioxidant properties to protect hypertensive animals against mortality and vascular damage, to reduce cholesterol levels from the vessel wall of hypercholesterolaemic animals, and to reduce the progression of existing atherosclerotic lesions. The clinical benefit of lacidipine in atherosclerosis has recently been confirmed in humans in a large, multicentre, comparative, 4-year clinical trial involving patients with mild to moderate hypertension. The European Lacidipine Study on Atherosclerosis (ELSA) showed that lacidipine was able to slow the progression of atherosclerosis, measured as carotid intimato-media thickness, by 40% compared with atenolol (p = 0.0073). Although further comparative trials are needed, based on the results of ELSA, lacidipine is likely to become a promising therapeutic agent for atherosclerosis.
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PMID:Endothelial dysfunction, hypertension and atherosclerosis. A review of the effects of lacidipine. 1245 52

Similarities and dissimilarities of 3 third generation calcium antagonist (amlodipine, lacidipine and lercanidipine) are presented. Lacidipine is characterized by prolonged antihypertensive action despite its plasma half life is just about 14 hours. Duration of lacidipine effect can be explained by accumulation in lipid bilayer of cellular membranes where it interacts with calcium channels. Pharmacodynamics of lacidipine is discussed in detail as well as experience of its use in hypertension including data of ELSA study which has demonstrated ability of lacidipine to inhibit progression of carotid artery atherosclerosis.
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PMID:[Third generation of calcium antagonists: focus on lacidipine]. 1249 25

Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from 111 men with established hypertension (diastolic pressure >95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure <80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives ( P =0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.
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PMID:Circulating oxidized low-density lipoprotein is increased in hypertension. 1283 27


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