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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this review is to present an overview of the results of randomized primary preventive trials with beta-blockers in patients with hypertension. For statistical and biological reasons, any preventive effect on coronary events is hard to demonstrate in women in these primary preventive trials because of the low incidence of coronary events in middle-aged, white women. Therefore, special attention will be focused on the effect in men. Four beta-blockers have been studied: propranolol, oxprenolol, atenolol, and metoprolol. Results from the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed that the risk for coronary events was 24% lower in patients receiving beta-blockade compared with patients receiving diuretics (p less than 0.001). In men, three beta-blockers (propranolol, oxprenolol, and metoprolol) have shown significantly lower risk for coronary events (fatal and nonfatal) in the nonsmoking subgroup. Results from the MAPHY study also indicated a reduction in total and coronary mortality with the beta-blocker as compared with thiazide diuretics. The observed reduced risk for coronary events with beta-blockers as compared with diuretics is probably independent of the reduction in blood pressure. Mechanisms currently under study include antiatherosclerotic effects, antithrombotic effects, anti-ischemic effects, and antifibrillatory effects. It is not possible to judge, with present evidence, if all beta-blockers are equally effective in preventing sudden death and other coronary events.
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PMID:Beta-blockade in the primary prevention of coronary heart disease in hypertensive patients. Review of present evidence. 168 15

Because hypertension is a major risk factor for cardiovascular disease it would be expected that therapeutic reduction of blood pressure would protect patients from coronary heart disease (CHD). Twelve long-term trials involving over 40,000 patients have been performed to study the effectiveness of diuretics and beta-blockers in controlling blood pressure and reducing cardiovascular morbidity and mortality. However, no other drugs have been tested. The Hypertension Detection and Follow-up Program, European Working Party in the Elderly and the Metoprolol Atherosclerosis Prevention in Hypertension trial were the only studies where a significant reduction in total, cardiac and cardiovascular mortality were observed. Moreover three large trials have demonstrated some reduction in CHD among male nonsmokers. This review examines all these trials as well as some of the reasons for this disappointing outcome. New trials using modern antihypertensive drugs should be performed to analyze whether they contribute directly to protection from coronary events and other cardiovascular complications.
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PMID:[Effect of antihypertensive therapy on the prevalence of ischemic cardiopathy in arterial hypertension. New contributions]. 218 56

The effects of 3 beta-blockers with different pharmacological properties (non-selective: propranolol; beta 1-selective: metoprolol; and with intrinsic sympathomimetic activity: pindolol) were comparatively studied on LDL and lipid metabolism in human fibroblasts. At 10(-4) M, propranolol increased low density lipoprotein binding, uptake and degradation by 1.5-, 2.2- and 1.8-fold, respectively, whereas metoprolol and pindolol had no effect. This effect of propranolol is mainly due to an increase in LDL receptor number. Propranolol also enhanced sterol, triacylglycerol, fatty acid and phospholipid synthesis by 2-3-fold from sodium acetate. Cholesterol esterification by oleic acid was significantly and specifically decreased 4-fold by propranolol. Metoprolol and pindolol affect neither sterol synthesis nor cholesterol esterification. Pretreatment of cultured fibroblasts with propranolol induced an increase in hydroxymethyl-glutaryl-coenzyme A reductase activity and a decrease in acyl-coenzyme A: cholesterol-O-acyltransferase (ACAT) activity. Propranolol inhibited the induction of ACAT activity by exogenous cholesterol. Preincubation of a cell-free extract with propranolol also induced inhibition of ACAT activity. Propranolol decreased the cholesteryl ester content of cultured cells. These effects of propranolol on LDL and cholesterol metabolism might be related to the amphiphilic properties of the drug and suggest an effect on the cholesterol intracellular traffic. The decrease in cholesterol esterification and in the cholesteryl ester cellular level induced by propranolol may be involved in its antagonizing effect on experimental atherogenesis.
Atherosclerosis 1990 Mar
PMID:The antihypertensive drug propranolol enhances LDL catabolism and alters cholesterol metabolism in human cultured fibroblasts. 232 24

Various antihypertensive agents were studied in vitro to determine their effects on cholesterol esterification by arterial ACAT (acylCoA:cholesterol acyltransferase; E.C. 2.3.1.26) and on the activity of plasma LCAT (lecithin:cholesterol acyltransferase; E.C. 2.3.1.43). Propranolol inhibited ACAT in normal rat aorta, atheromatous rabbit aorta, and in isolated microsomes from atheromatous rabbit aorta, and in isolated microsomes from atheromatous rabbit aorta. Inhibition reached 50% in microsomes at approximately 0.8 mM. Metoprolol, prazosin, and chlorthalidone also inhibited microsomal ACAT, but to a lesser extent than propranolol; nadolol had no effect on the enzyme. Propranolol, metoprolol, prazosin, and chlorthalidone also inhibited LCAT in human plasma, whereas nadolol showed no inhibitory effect. Fifty percent inhibition occurred at 2 mM with prazosin and chlorthalidone and at 4-5 mM with propranolol. Metoprolol showed a weak dose-dependent inhibition that ranged from 2 to 10% over the concentration range 0.5-5 mM. The data suggest a mechanistic basis for altered lipoprotein profiles observed clinically with certain antihypertensive therapies and suggest that a direct effect of beta-blockers on arterial wall metabolism may account for their recognized ability to reduce the development of experimental atherosclerosis and to improve survival in post-myocardial infarction patients.
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PMID:Effects of antihypertensive agents propranolol, metoprolol, nadolol, prazosin, and chlorthalidone on ACAT activity in rabbit and rat aortas and on LCAT activity in human plasma in vitro. 241 Jun 71

Metoprolol has been on the market for 10 years; the research, however, started nearly 20 years earlier and clinical research some 17 years ago. Metoprolol has been and is still subject to intensive research, which has resulted in evidence for its cardiovascular protective effects in coronary heart disease, cardiovascular hypertrophy and atherosclerosis. The properties making the beta 1-selective blocker metoprolol a cardioprotective drug and pharmaceutical development improving the qualities of the substance are also discussed in this review.
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PMID:Ten years of clinical experience with metoprolol. 248 Nov 76

A number of long-term clinical trials involving over 40,000 patients have been performed to study the effectiveness of antihypertensive therapy in controlling high blood pressure and in reducing the morbidity and mortality associated with hypertension. Only diuretics and beta blockers have been studied in long-term trials to determine their efficacy in reducing cardiovascular morbidity and mortality. The Hypertension Detection and Follow-Up Program (HDFP), Medical Research Council (MRC) trial, European Working Party on Hypertension in the Elderly (EWPHE) trial, Australian Therapeutic Trial in Mild Hypertension, and the Veterans Administration Cooperative Study all showed a reduction in stroke rate. The EWPHE and HDFP trials were the only studies to show a statistically significant reduction in mortality from myocardial infarction. All of these were diuretic-based; in addition, the MRC trial also used a beta blocker as first-step therapy in 1 cohort. The International Primary Prospective Prevention Study in Hypertension and Heart Attack Primary Prevention in Hypertension (HAPPHY) trials compared beta-blocker and non-beta-blocker or diuretic-based therapies and found no significant difference between the treatment groups in the incidence of stroke or cardiac events. Neither study had a control group, so it was impossible to determine if there was any reduction in stroke or cardiac events. The Metoprolol Atherosclerosis Prevention in Hypertension trial, an extension of the HAPPHY trial, showed that smokers receiving the beta blocker metoprolol had a significantly lower cardiovascular mortality rate than those randomized to a diuretic drug. However, subgroup analysis of the HAPPHY data showed no differences in the effect of beta blockers and diuretics in smokers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of the long-term controlled trials of usefulness of therapy for systemic hypertension. 256 89

The question whether initial antihypertensive treatment with a beta-blocker prevents hypertensive complications better than initial treatment with a non-betablocker, mainly diuretic based treatment, has been studied in recent large-scale studies like the Medical Research Council (MRC) trial, the International Prospective Primary Prevention Study in Hypertension (IPPPSH), the Heart Attack Primary Prevention in Hypertension (HAPPHY) study and the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) study. The first three studies were unable to find a more beneficial effect of beta-blockers than of thiazide diuretics. The MAPHY study, however, found a lower total mortality, in the metoprolol treated group than in the diuretic treated. As the HAPPHY and MAPHY studies share a substantial part of patient-years and number of deaths, these diverging results have evoked confusion and debate. This paper presents the main results of both studies and discusses the possible reasons for the different outcome.
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PMID:Beta-blockers and diuretics. The HAPPHY and MAPHY studies. 257 34

Benzothiadiazine diuretic agents and beta-adrenergic receptor-blocking drugs are two of the main groups of drugs used to treat mild hypertension. Recently, questions have been raised about their relative efficacy in preventing morbidity and mortality from vascular disease in addition to their effect on lowering blood pressure. Attention has been focused on the unfavorable metabolic effects of diuretic drugs and the proven value of beta-adrenergic receptor blockade in secondary prevention after myocardial infarction. Four randomized controlled trials comparing drugs in these two classes have been published: the Medical Research Council trial, the International Prospective Primary Prevention Study in Hypertension, the Heart Attack Primary Prevention in Hypertension trial, and the Metoprolol Atherosclerosis Prevention in Hypertension study. These trials, especially that of the Medical Research Council, have raised some questions about the relative efficacy of these two classes of drugs in preventing stroke in smokers and nonsmokers. Overall, there is little evidence of a reduction in morbidity and mortality after myocardial infarction. The predicted advantage of beta-adrenergic receptor blockade over diuretic therapy has not been realized although there are sufficient hints of a differential benefit to encourage the performance of further trials.
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PMID:Diuretic agents and beta-blockers in the treatment of hypertension. 257 61

The purpose of the present study was to characterize possible effects of dietary-induced plasma lipid elevations on the development of arterial lesions in spontaneously hypertensive rats (SHR) and to reveal any influence of treatment with metoprolol on these parameters. Metoprolol treatment caused an 8% decrease in heart rate and a 13% decrease in blood pressure and led to a rise in plasma triglycerides, 24%, 17% and 34% after 1, 3 and 6 months of metoprolol treatment, respectively. However, no effect on plasma triglycerides was observed after 9 months of metoprolol treatment while a reduced cholesterolemic response was observed. Intimal proliferations containing accumulations of lipids were observed in small intramural branches of coronary arteries (greater than 100 microns) in 11 of 31 control rats fed the atherogenic diet for 9 months. In contrast, similar changes were observed in only 1 of 34 metoprolol-treated rats fed an otherwise identical diet. The corresponding figures for the frequency of lipid containing intimal plaques in aorta were 6/19 in controls and 2/24 in the metoprolol-treated group.
Atherosclerosis 1989 Dec
PMID:Effect of metoprolol on plasma lipids and arterial intimal lipid deposition in spontaneously hypertensive rats. 261 Jul 25

These studies have examined the effects of dl-propranolol, d-propranolol, and metoprolol on aortic atherogenesis in the cholesterol-fed rabbit and have correlated the vascular effects of the drugs with their influence on blood pressure, plasma lipids and lipoproteins, arterial metabolism, and arterial permeability. dl-Propranolol, and, to a lesser extent, d-propranolol, used in clinically relevant doses of 5 mg/kg body weight per day, inhibited the development of aortic atherosclerosis in association with significant reductions in aortic free and esterified cholesterol content. No significant effects of the drugs on blood pressure or on the total amounts or types of circulating lipoproteins were apparent. Accumulation of cholesterol in the liver and adrenal gland was not influenced by propranolol. Aortic acyl CoA:cholesterol acyltransferase and lysosomal enzyme activities were reduced by propranolol administration, but the inhibition may have been secondary to the lesser degrees of atherosclerosis and cholesterol accumulation present. In vitro inhibition of acyl CoA:cholesterol acyltransferase activity by either dl- or d-propranolol was also observed, but occurred only at propranolol concentrations of 10(-3) M or greater. Treatment with dl-propranolol had no significant effect on the rate of transport of labeled albumin across the isolated carotid artery of cholesterol-fed rabbits. Metoprolol administration (6.25 mg/kg body weight per day) had no significant influence on atherogenesis or arterial metabolism in this model. The results suggest that propranolol inhibits in part the development of atherosclerosis in the cholesterol-fed rabbit, and that the effect may be related to a direct action on the arterial wall.
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PMID:Effects of propranolol on atherogenesis in the cholesterol-fed rabbit. 399 1


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