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

Patients leaving the hospital after a myocardial infarction are given a prescription containing several drugs. The purpose of this paper is to determine which of these drugs have a proven value and for which types of patients. Antithrombotic agents (be it acetyl-salicylic acid or antivitamin K drugs) have been shown to be efficient after a myocardial infarction. Beta-blockers are certainly useful, notably in cases with severe necrosis. Conversely, the usefulness of calcium antagonists for secondary prevention has not been demonstrated and indeed, it seems probable that the drugs of this class might be harmful in patients who had severe infarction. There is little divergence concerning the necessity to control the risk factors for coronary atherosclerosis after a myocardial infarction. The evidence is strong concerning giving up smoking; it is intuitive as regards controlling arterial hypertension and more controversial as regards the need for lowering blood cholesterol levels. The systematic prescription of antiarrhythmic agents after myocardial is certainly noxious. Finally, prospects are now opened by the prevention of left ventricular remodelling under treatment with angiotensin-converting enzyme inhibitors.
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PMID:[Which medical treatment after myocardial infarction?]. 136 53

Results of animal studies suggest that calcium antagonists can inhibit the development of experimentally induced atherosclerosis. Although the biological process underlying this phenomenon has not been fully elucidated, several mechanisms have been proposed. Notably, calcium antagonists may suppress free radical-induced damage of the vascular endothelial cells with the consequent transport of low-density lipoproteins across the vascular endothelium and the accumulation of the lipids in the intima. Studies have shown that calcium antagonists can inhibit the stimulatory effects of epidermal growth factor on intracellular calcium concentrations and DNA synthesis in cultured rat aortic smooth muscle cells, but not those of platelet-derived growth factor or somatomedin C. Further experimental studies have demonstrated that calcium antagonists stimulate prostacyclin production and inhibit 12-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration, therefore preventing platelet aggregation and intimal thickening, respectively. Despite the encouraging results in animals, comparatively few clinical studies have been undertaken to establish the efficacy of calcium antagonists in the prevention of cardiovascular disease in hypertensive patients. This, in part, is due to the technical difficulties associated with measuring coronary artery stenosis, but the recent development of a technique for the video-densitometric analysis of coronary angiograms has enabled stenotic regions to be quantified. Using this approach, a retrospective study has been undertaken of the efficacy of long-term treatment with a calcium antagonist on the progression of coronary atherosclerosis. Results are encouraging and a prospective long-term, multicenter trial is proposed.
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PMID:The role of calcium antagonists in the treatment of atherosclerosis and hypertension. 136 1

Although clinical trials of the efficacy of antihypertensive treatment have demonstrated impressive reductions in the incidence of stroke, the reduction in coronary artery disease mortality has been less impressive. It may be that the antihypertensive drugs used in these trials induced metabolic disturbances, or produced inadequate regression of left ventricular hypertrophy, thus blunting the reduction in risk of coronary artery disease expected with blood pressure-lowering. Isradipine, a dihydropyridine calcium antagonist known to be an effective antihypertensive agent, has also displayed pronounced antiatherogenic effects in animals. Thus, a reasonable hypothesis could be that isradipine not only reduces the level of blood pressure, but also may have a positive effect on the evolution of atherosclerotic plaque in coronary and carotid arteries, thereby leading to prevention of clinical sequelae of atherosclerosis. On this basis, a 3-year clinical trial is being carried out in the United States--the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS)--to establish the efficacy of isradipine in inhibiting atherogenesis and retarding the progression of atherosclerosis in carotid arteries of hypertensive patients. The primary end point of the study is intima-media thickness and the extent of atherosclerotic plaque in the carotid arteries, as measured by B-mode ultrasonography.
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PMID:MIDAS: hypertension and atherosclerosis. A trial of the effects of antihypertensive drug treatment on atherosclerosis. MIDAS Research Group. 137 28

Epidemiological studies indicate that there are biological interrelationships between blood pressure and blood lipids that may influence the mechanisms whereby hypertension is associated with an increased risk of coronary artery disease. Serotonin (5-HT) and thromboxane A2, which are released from aggregating platelets, mediate platelet-induced vasoconstriction, which itself significantly contributes to coronary artery constriction in vivo. Platelet aggregatory response to serotonin is modulated by disparate effects of lipoprotein fractions. This corresponds to the recognized differences in degree of atherogenicity of low- (LDL) and high-density lipoprotein (HDL). Amplification of serotonin-induced platelet aggregation by LDL and its inhibition by HDL support the hypothesis that 5-HT-mediated effects represent a mechanism clinically relevant to both chronic progression of atherosclerosis (particularly at sites of vascular injury and atherosclerotic plaques) and acute thrombotic events. Calcium antagonists differ in their platelet-inhibition potency, including their effects on platelet response to 5-HT and LDL. Verapamil and isradipine inhibit platelet aggregation induced by 5-HT at therapeutic concentrations. Isradipine also inhibits the amplifying effect of LDL on 5-HT-induced aggregation. These platelet effects of calcium antagonists appear to be neither group- nor class-specific but, rather, drug-specific.
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PMID:Platelet activation by low-density lipoprotein and serotonin: effects of calcium antagonists. 137 30

Isradipine, a calcium antagonist of the dihydropyridine type, shows antiatherosclerotic actions that interfere with all three main mechanisms of atherosclerosis. These actions are mediated by the release of prostaglandin I2 and endothelium-derived relaxing factor, and the subsequent elevation of intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate, respectively. These mechanisms have been proven in vitro and in animal models. Preliminary data in humans suggest that these mechanisms have clinical relevance in the long-term treatment of patients as well.
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PMID:Antiatherosclerotic actions of isradipine. 137 31

Three key players in the humoral-cellular interactions that occur during the early development of atherosclerosis are presented as they activate platelets and vascular smooth muscle cells but eventually can be corrected by calcium-channel blockers. Platelet-activating factors via phospholipase C and phosphoinositides increase cytosolic calcium and phosphorylate contractile proteins, thereby inducing a change--aggregation and the secretory response of platelets. Low-density lipoprotein (LDL) has a similar hormone-like action and activates the signal transfer cascade that eventually leads to platelet aggregation as well as vascular smooth muscle cell proliferation. These effects can be greatly reduced by high-density lipoproteins. Platelet-derived growth factor stimulates the transcription of the LDL-receptor gene as well as the HMG-CoA reductase gene. The latter is inhibited by calcium-channel antagonists while the former is further enhanced. Thus, calcium-channel antagonists interfere with the stimulus-response coupling not only via slow calcium-channel influx inhibition but also by an additional membrane action and interference with gene activation.
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PMID:Atherosclerosis, cell motility, calcium, and calcium-channel blockers. 137 97

Calcium is a ubiquitous cation involved in a wide variety of physiological processes. Normally, cytosolic calcium is maintained within narrow limits but under certain conditions the levels rise--either because of excess calcium entry, internal release, or failure of the extrusion mechanisms. Such conditions include hypertension and myocardial ischemia. Calcium ions are also involved in the formation of atherosclerotic lesions. Hypertension, ischemic heart disease, and atherosclerosis are all amenable to calcium antagonist therapy. The efficacy of this class of drugs in the management of such a wide spectrum of disorders is in accord with the central role played by calcium in the etiology of these disorders. To some extent, however, the disorders are interrelated, with hypertension being a major risk factors for ischemic heart disease and atherosclerosis.
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PMID:Calcium, calcium antagonism, atherosclerosis, and ischemia. 137 99

Calcium antagonists are useful for the management of patients with ischaemic heart disease, particularly when used prophylactically. At the cellular level, these drugs act primarily by limiting calcium ion (Ca++) entry through the voltage-sensitive Ca(++)-selective channels, an effect that contributes markedly to their 'energy sparing' properties. However, the long term use of these drugs has additional advantages, particularly with respect to their ability to slow Ca(++)-dependent processes involved in the formation of atherogenic lesions, partially antagonise the effects of the raised levels of circulating endothelin-1 encountered during ischaemia-induced heart failure and hypertension, and trap and immobilise oxyradicals. Prolonged episodes of ischaemia result in an irreversible loss of homeostasis with respect to Ca++. However, the increase in myocardial cytosolic Ca++ caused by relatively short periods of ischaemia is small, reversible, and markedly attenuated by the prophylactic use of calcium antagonists. In the isolated, perfused rat heart, verapamil pretreatment produces statistically significant inhibition of the increase in cytosolic Ca++ during 20-minute global ischaemia. This stereospecific effect is associated with a decrease in the rise in total tissue Ca++ during reperfusion and amelioration of the adenosine triphosphate depletion caused by ischaemia. In general, discussion relating to the molecular basis of the use of calcium antagonists in the management of patients with ischaemic heart disease needs to take into account the duration of the ischaemic event, the workload on the myocardium, the need for prophylactic therapy, and the presence of exacerbating factors such as atherosclerosis and tobacco smoking. The early rise in cytosolic Ca++, the source of which remains uncertain, appears to be an important focus for anti-ischaemic drug therapy.
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PMID:The molecular basis for the use of calcium antagonists in ischaemic heart disease. 137 84

Recent multicentre studies evaluating the therapeutic value of calcium antagonists in reducing the incidence of cardiovascular complications after myocardial infarction (secondary prevention) and in retarding the development of atherosclerosis in coronary artery disease (tertiary protection) are reviewed. The prognosis of patients after acute myocardial infarction can be improved not only by interventional measures such as aortocoronary bypass surgery or percutaneous transluminal catheter angioplasty, but also by various drugs. Numerous studies have shown that beta-blockers and platelet aggregation inhibitors can reduce mortality and reinfarction rates. Calcium antagonists in secondary prevention trials after acute myocardial infarction, however, have produced variable results. Whereas the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) [Israeli SPRINT Study Group 1988] with nifedipine showed no beneficial effect of the drug, studies with verapamil in the Danish Verapamil Infarction Trial II (DAVIT II) [Danish Study Group on Verapamil in Myocardial Infarction 1990] and diltiazem in the Multicentre Diltiazem Postinfarction Trial (MDPIT) [Multicenter Diltiazem Postinfarction Trial Research Group 1988] as secondary prevention have demonstrated improvements in survival and cardiovascular complications, but these improvements were restricted to patients without heart failure. In view of the ability of calcium antagonists to reduce atheroma progression in coronary artery disease in animal models, the antiatherosclerotic effects of these agents in clinical studies have generally been disappointing. In the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) [Lichtlen et al. 1990], however, nifedipine treatment was associated with a 28% reduction in new lesion development, but did not affect the development of severe lesions. Similar results have been obtained with nicardipine.
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PMID:Secondary and tertiary prevention with calcium antagonists in coronary artery disease. 137 87

Primarily hypervolaemic, high output forms of hypertension, with features indicating or strongly suggesting fluid overload as the cause of elevated cardiac output, resulting from renal disease with reduced glomerular filtration rate causing sodium retention, renal tubular causes of sodium retention, greatly excessive sodium intake and low renin hypertension, can be treated by reduction of sodium intake and potentiation of its excretion by diuretic therapy, removal of the cause (e.g. aldosteronoma), and calcium antagonists. Excessive vasoconstriction resulting from noradrenaline (norepinephrine) in neurogenic hypertension, phaeochromocytoma, orthostatic hypertension and alpha-adrenergic drug administration; angiotensin excess due to renal ischaemia brought about by aortic coarctation, renal arterial and arteriolar stenosis, intraluminal obstruction, external renal compression, renin-producing tumours, intrinsic kidney diseases and excessive renin substrate; and vascular structural disorders such as atherosclerosis, arteriolitides and fibrosis with or without calcification of major arteries may also induce hypertension. Secondary hypertension of uncertain mechanism may occur in hyperparathyroidism, hyper-or hypothyroidism, or acromegaly. All are best treated by appropriate correction of the endocrine excess or deficiency. It may also occur in pregnancy, where the mechanism may involve prostaglandin-thromboxane imbalance or calcium deficiency; calcium deficiency with some evidence of benefit from calcium supplements; and the recumbent hypertension paradoxically associated with autonomic failure. Excellent responses to specific correction of the underlying cause or pathogenetic mechanism is usual in young individuals but less frequent in older patients.
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PMID:Secondary hypertension. An overview of its causes and management. 137 54


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