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

The anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trail of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50, 75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 microM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.
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PMID:Platelet anti-aggregating activity and tolerance of clopidogrel in atherosclerotic patients. 897 14

Dysfunction of vascular smooth muscle (VSM) is at the center of occlusive disorders of the cardiovascular system such as hypertension, atherosclerosis, coronary artery disease and hypoxia. In addition to circulating biogenic amines and various neurotransmitters originating from the central nervous system and endocrine system, various autocoids of arachidonic acid metabolism in the blood as well as in the endothelium play an important regulatory role in the maintenance of the tone and the contractile function of VSM. A monolayer of endothelial cells lining the heart and large blood vessels is responsible for producing and releasing both endocrine and paracrine substances such as endothelins, nitric oxide, prostaglandins and prostacyclins. Aspirin, (acetylsalicylic acid/ASA) an ancient remedy against fever and pain, is emerging as an effective drug not only against occlusive disorders but also against various cancers and the AIDs virus. During pregnancy induced hypertension (PIH) and in occlusive disorders, aspirin provides relief through inhibition of cyclooxygenase, an enzyme required for the metabolism of arachidonic acid to produce prostaglandins and prostacyclins in platelets and in endothelial cells. Because of its unique molecular constitution, synergistic ability and solubility in the lipidic environment, various mechanisms of aspirin's actions are being currently investigated. In this review, the effect of aspirin on the regulation of VSM in the presence and absence of endothelium are discussed.
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PMID:Vascular smooth muscle, endothelial regulation and effects of aspirin in hypertension. 955 99

Arterial thrombosis frequently leads to death or disability from stroke, peripheral arterial disease, or myocardial infarction (MI). Treating the underlying causes of these diseases is the key to producing significant reduction in morbidity, mortality, and health care costs. Prevention of arterial thrombosis is the primary indication for antiplatelet therapy, and intense research has been conducted in the past decade to develop novel antiplatelet agents with favorable safety profiles. The results of the Antiplatelet Trialists' Collaboration, which definitively established the rationale for antiplatelet agents in the prevention of death, MI, and stroke, were an important stimulus for this research. This large meta-analysis combined data from 145 randomized trials and showed that antiplatelet therapy (most commonly aspirin, 75 to 325 mg/d) reduced the risk of vascular events, including nonfatal MI, nonfatal stroke, and vascular death, by 25% in patients at high risk for occlusive vascular disease. The limitations and adverse effects associated with traditional antiplatelet agents such as aspirin have prompted the search for newer antiplatelet agents. Clinical trials such as the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study, which was the first study to evaluate aspirin and clopidogrel in patients with cerebrovascular, cardiac, and peripheral arterial disease, have established the importance of newer antiplatelet effects in the management of patients with diseases associated with atherosclerosis. The pathophysiology of atherosclerosis, the mechanisms of action of antiplatelet agents, and the results of these and other clinical trials that document the value of antiplatelet agents in atherosclerosis are reviewed in this paper.
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PMID:Antiplatelet therapy in atherosclerotic cardiovascular disease. 958 29

Coronary artery ectasia is an uncommon expression of coronary artery atherosclerosis and other diseases. It occurs in about 1.4 percent of the adult population. It is not distinguishable from obstructive coronary artery disease in severity of angina, clinical presentation, electrocardiograms, mortality, or outcome of coronary artery surgery. Although there is debate, treatment is indicated in the form of chronic warfarin anticoagulation to prevent coronary thrombus formation and its sequelae. Aspirin therapy may suffice in asymptomatic individuals.
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PMID:Coronary artery ectasia. 960 23

Human cytomegalovirus (CMV) infection of smooth muscle cells generates reactive oxygen species (ROS) and thereby activates nuclear factor kappaB (NFkappaB), which causes expression of viral and cellular genes involved in immune and inflammatory responses. These changes could account for the mounting evidence suggesting that CMV may contribute causally to restenosis and atherosclerosis. We found that CMV induces ROS, at least partly, through a cyclooxygenase-2 (COX-2)-dependent pathway. Moreover, the viral immediate-early (IE) gene products, IE72 and IE84, have the capacity to transactivate the COX-2 promoter. Aspirin and indomethacin, both cyclooxygenase inhibitors as well as direct ROS scavengers, reduce CMV-induced ROS, probably through both of these activities. Sodium salicylate also has antiviral effects as the result of its potent antioxidant properties. Furthermore, by reducing ROS, aspirin and sodium salicylate inhibit CMV-induced NFkappaB activation, the ability of IE72 to transactivate its promoter, CMV IE gene expression after infection of SMCs, and CMV replication in SMCs. This is the first time aspirin has been shown to have antiviral effects. Thus, it is possible that aspirin has previously unrecognized therapeutic effects in various clinical situations, such as in viral infections (when used as an antipyretic agent) and in atherosclerosis (when used as an antiplatelet agent).
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PMID:Aspirin attenuates cytomegalovirus infectivity and gene expression mediated by cyclooxygenase-2 in coronary artery smooth muscle cells. 968 61

Smoking causes atherosclerosis, and smokers have increased thromboxane (TXA2) formation. As aspirin inhibits TXA2 production we speculated that smokers would preferentially profit from inhibition of the TXA2 pathway by aspirin. Increased expression of P-selectin, a constituent of the alpha-granules of platelets, and increased levels of circulating (c)P-selectin in plasma are markers for platelet activation. The aim of this study was to compare P-selectin expression on platelets between smokers and nonsmokers, and to compare with placebo the effect of 2 weeks administration of 100 mg/d aspirin on platelet activation in smokers. Smokers exhibited higher P-selectin expression on platelets than non-smokers (2.7+/-1.8% v 1.6+/-0.6%, P=0.018), thus confirming increased platelet activation. Aspirin did not reduce platelet activation as demonstrated by unchanged P-selectin expression on platelets and cP-selectin plasma levels.
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PMID:Low-dose aspirin does not lower in vivo platelet activation in healthy smokers. 975 50

Angioplasty and bypass surgery have become standard methods of treating patients with symptomatic coronary atherosclerosis but restenosis remains the major limitation of percutaneous coronary revascularization. In pharmacological management of restenosis after coronary intervention multiple agents have been tried, with mostly discouraging results. Aspirin, dipyridamole, ticlopidine, heparin. Hirudin, and warfarin has failed to show beneficial effects on restenosis. Of all antithrombotics, only an inhibitor of the platelet IIb/IIIa integrin, which may lead to early vessel changes, leading to decrease restenosis. Antiproliferative agent (trapidil and angiopeptin) and probucol have also resulted in improved restenosis rate. In patients after bypass surgery with some degree of hyperlipidemia intensive lipid-lowering therapy is beneficial in slowing the late progressions of atherosclerosis as well as graft occlusion.
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PMID:[Pharmacological treatment of restenosis after coronary angioplasty and bypass grafting]. 977 Oct 20

The risk factors, epidemiology, diagnosis, and treatment of peripheral arterial disease are reviewed. Peripheral arterial disease is characterized by a gradual reduction in blood flow to one or more limbs secondary to atherosclerosis. Risk factors include smoking, diabetes mellitus, hyperlipidemia, and hypertension. The most common clinical manifestation is intermittent claudication. The prevalence of intermittent claudication in people over the age of 50 is 2-7% for men and 1-2% for women. The ankle:brachial pressure index (ABPI) is a useful measure of disease severity; an ABPI of 0.5-0.9 is common in intermittent claudication. The goals of therapy are to relieve or reduce ischemic symptoms, alleviate disability, improve in functional capacity, prevent progression that may result in gangrene and limb loss, and prevent cardiovascular and cerebrovascular events. Treatment includes risk-factor modification, drug therapy (primarily with antiplatelet agents), and revascularization procedures. Aspirin has been shown to be effective in reducing the associated risk of myocardial infarction and stroke. Ticlopidine appears to be a reasonable alternative for patients who are hypersensitive to aspirin. Clopidogrel has been shown to be more effective than aspirin in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease. There is controversy over the appropriate treatment for acute arterial occlusions. Risk-factor modification and antiplatelet drugs are the mainstays of therapy for patients with intermittent claudication, the most common manifestation of peripheral arterial disease.
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PMID:Management of peripheral arterial disease. 978 99

Atherosclerosis of the cerebral arteries is the main cause of cerebral infarction but the frequency with which this cause is implicated is very variable from one trial to another depending on the criteria used. Primary prevention of this type of infarction is mostly based on the correction of arterial risk factors and on carotid artery surgery in selected cases. Aspirin does not appear to the effective in this indication. The respective indications of heparin and aspirin in the acute phase of cerebral infarction remain controversial despite the recent publications of large scale therapeutic trials. The benefits of these treatments is, at best, globally modest. Thrombolytics could, on the other hand, revolutionize the treatment of acute cerebral infarction if the encouraging results of a recent trial using rt-PA in the first 3 hours, are confirmed by other trials. After the acute phase, antiplatelet agents (aspirin, ticlopidine, clopidogrel or aspirin associated with dipyridamole) and surgery in patients with symptomatic carotid artery stenosis greater than 50% or 70-80% (according to the method of measurement) have been shown to be effective. Several large scale trials are under way to assess the benefits and risks: a) of antihypertensive therapy in patients with previous cerebrovascular accidents, b) of treatment with statins of patients at high risk of infarction due to atherosclerosis, c) of oral anticoagulants at low dosage (versus antiplatelet agents) in secondary prevention, d) of thrombolytics in the acute phase of cerebral infarction, e) of carotid angioplasty (versus surgery) in patients with symptomatic severe stenosis.
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PMID:[Prevention of cerebral infarct caused by atherosclerosis]. 983 82

The trapping of apolipoprotein (apo)B containing lipoproteins within the arterial subendothelial matrix (ECM) is an early event in atherosclerosis. When lipoprotein lipase, a constituent of the ECM, is prebound to ECM both LDL and oxidized LDL binding is greatly enhanced. In this study we compared the binding of lipoprotein(a) (Lp(a)), a lipoprotein correlated with atherosclerosis and restenosis, to ECM in the presence of varying concentrations of LPL. Without LPL, Lp(a) binding was low and non-saturable. In the presence of LPL, Lp(a) retention increased from 2.7 x 10(-7) to 1.13 x 10(-4) nmoles. Scatchard analysis demonstrated that the affinities of both Lp(a) and LDL to lipase were similar. In competition experiments, LDL, apoE, polymers of lysine and arginine were all capable of preventing the lipase specific [125I]Lp(a) retention. However, neither collagen nor fibronectin were capable of blocking or displacing [125I]Lp(a) from the lipase bound to ECM. In a separate set of experiments, when ECM was not saturated with lipase, both fibronectin and collagen (at 10-fold protein excess) prevented approximately 40% of total [125I]Lp(a) retention to ECM. These data suggest, in the absence of lipase, apo(a) may regulate the binding of Lp(a) to ECM. Whereas, lipase enhanced the binding of Lp(a) to ECM, most probably through the apoB moiety of the Lp(a) particle.
Atherosclerosis 1999 Jan
PMID:Lipoprotein lipase greatly enhances the retention of lipoprotein(a) to endothelial cell-matrix. 992 May 9


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