Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin is a well-established medication in the treatment of atherothrombotic vascular disease. However, despite aspirin treatment a substantial number of patients experience recurring ischaemic episodes. Aspirin resistance denotes those situations when it is unable to protect individuals from thrombotic complications, or when it fails to produce an anticipated effect in laboratory tests of platelet function. There are various laboratory techniques with which to evaluate the effectiveness of aspirin and other antiplatelet drugs. It has been estimated that in 5-60% of patients, aspirin does not achieve adequate efficacy in various measures of platelet activity. Some studies have revealed that vascular patients shown by laboratory tests to be aspirin-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance, among others, include genetic polymorphisms, alternate pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or low aspirin dose. An increase in the dosage of aspirin or conversion to clopidogrel or clopidogrel plus aspirin might be beneficial in the management of those patients who are aspirin resistant. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selecting the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events.
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PMID:Aspirin resistance in stroke: 2004. 1576 Jun 36

Arterial wall injury caused by percutaneous coronary intervention (PCI) triggers transient platelet activation and mural thrombosis; these effects are superimposed on the preexisting platelet hyperreactivity associated with underlying atherothrombosis. Platelet activation has been implicated in the major complications of PCI: acute and subacute thrombosis and restenosis. Antithrombotic and anticoagulant therapy minimizes thrombotic complications after PCI. Aspirin plus a thienopyridine (ticlopidine or clopidogrel) is more effective than aspirin plus heparin and extended warfarin therapy in preventing periprocedural ischemic events and subsequent stent thrombosis and results in less major and minor bleeding. Dual antiplatelet therapy with aspirin and clopidogrel (the preferred thienopyridine because of its superior hematologic safety) is recommended for at least 4 weeks to prevent subacute stent thrombosis with bare-metal stents and 3 to 6 months to prevent late-stent thrombosis with drug-eluting stents. Coronary atherothrombosis is a diffuse vascular disease, and reduction of the risk of future ischemic events requires strategies that extend beyond the focal treatment of stenotic lesions. Optimal long-term care after PCI requires aggressive systemic pharmacotherapy (antiplatelet agents, statins, beta-blockers, and angiotensin-converting enzyme Inhibitors) in conjunction with therapeutic lifestyle changes (smoking cessation, weight reduction, dietary measures, and exercise). In this context, dual antiplatelet therapy (aspirin plus clopidogrel) is recommended for at least 12 months after PCI for prophylaxis of future atherothrombotic events.
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PMID:Long-term care after percutaneous coronary intervention: focus on the role of antiplatelet therapy. 1670 62

The development of drugs that selectively inhibit cyclooxygenase-2 (COX-2) demonstrates translational research from bench to bedside based on underlying knowledge of micro-cellular structure and function. However, theoretical concerns about potentially prothrombotic effects of selective COX-2 inhibitors coupled with observations of increased cardiovascular risk have produced significant consternation and lead to the withdrawal of two of these agents from the market. A number of questions remain unanswered. It appears clear that both selective and non-selective COX inhibitors are associated with increases in blood pressure. In addition, blood pressure is often increased after starting nonsteroidal therapy, and we know that even small increases in blood pressure in subjects with pre-existing vascular disease are associated with substantial increases in the risk of cardiovascular morbidity. Given this line of reasoning, one might hypothesize that the observed increases in the risk of cardiovascular events associated with COX-inhibitors are largely due to increases in blood pressure in populations of subjects who are already at high risk. But can we generalize that the adverse cardiovascular effects observed for rofecoxib and valdecoxib are sufficient to indict the entire class of COX-2 inhibitors, or is this not a class effect, but dependent upon the degree of COX-2 selectivity? In either case, it seems prudent to recommend that subjects who are at higher risk for a cardiovascular event and receiving a COX-inhibitor should also be treated with low dose ASA with close follow up of blood pressure and efficacious use of anti-hypertensive medications. Finally, modest dietary salt restriction may help lessen the effects of COX-inhibitors on blood pressure.
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PMID:COX-2 inhibitors and cardiovascular risk. 1761 50

Thrombosis superimposed on arteriosclerosis is the principal cause of mortality and morbidity in patients with arteriosclerosis. The use of antiplatelet agents and anticoagulants in the treatment of arteriosclerosis is well established, based on many large randomized trials. Aspirin is indicated for primary prevention in patients at increased risk of developing symptomatic atherosclerotic vascular disease. For patients with known vascular disease, antiplatelet therapy with aspirin is a well-established treatment. For high-risk patients such as those with acute coronary syndromes (ACS; unstable angina, myocardial infarction), dual antiplatelet therapy with aspirin and clopidogrel is indicated, based on results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. Platelet glycoprotein IIb/IIIa agents are powerful inhibitors of platelet function and are also effective in ACS, but the benefit is confined to high-risk patients. Anticoagulation with heparin or low-molecular-weight heparin (eg, enoxaparin) is also effective, with an approximately 50% reduction in cardiovascular events. These agents are also indicated for patients undergoing percutaneous coronary intervention. Prolonged dual antiplatelet therapy (at least 6 months) is recommended for patients receiving drug-eluting stents. The efficacy of antiplatelet therapy is thus well established in treating atherothrombosis, but aggressive therapy is associated with an increased bleeding risk. Newer agents may provide improved efficacy with a lower risk of bleeding.
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PMID:Use of antiplatelet agents and anticoagulants for cardiovascular disease: current standards and best practices. 1771 74

Atrial fibrillation (AF) is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Anticoagulant therapy reduces the risk of stroke, and the greatest benefit is seen in patients at highest absolute risk. Aspirin is a less effective alternative, and any benefit of aspirin might be due to its favourable effects on arterial thrombosis caused by vascular disease. However, anticoagulant therapy remains underused, particularly in the elderly, who probably have the most to gain from stroke prevention owing to their high absolute risk. The underuse of anticoagulation might also be related to uncertain risk of thromboembolism in individual patients and a perceived overestimation of the benefit and underestimation of risk of bleeding with warfarin in clinical trials. In this Review, we summarise the data for and against warfarin and aspirin therapies and discuss the clinical assessments and risk stratifications that guide the use of antithrombotic therapy for stroke prevention in patients with AF. Possible barriers to the uptake of anticoagulation therapy are also discussed.
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PMID:Atrial fibrillation and stroke prevention. 1794 52

Platelet and leucocyte activity are important in the acute development of thrombosis and in the pathogenesis of ischaemic vascular disease. Dan Shen Di Wan (DS, Cardiotonic Pill or Dantonic(R) Pill) is one of the most commonly used Chinese herbal formulations for treating patients with atherosclerotic disease in China and several Asian countries. We studied the effect of DS on platelet and leucocyte function and compared the effects with conventional antiplatelet agents, cangrelor (ADP P2Y(12) receptor antagonist) and aspirin (acetyl salicylic acid, ASA). Measurements were made by platelet aggregation (%) and activation (CD62P %), platelet-monocyte conjugate formation (P/M, CD42a median fluorescence, mf), platelet-neutrophil conjugate formation (P/N, mf), and leucocyte activation (CD11b median fluorescence on monocytes and neutrophils, mf) in response to 3.3 micromol/L adenosine diphosphate (ADP), 1.0 micromol/L platelet activating factor (PAF), 5.0 micromol/L adrenaline and 0.5 microg/mL collagen. We also evaluated the effect of its main component, water soluble extract of salvia miltiorrhiza (SME) on intracellular calcium mobilization in platelets triggered by 10 micromol/L ADP, 10 micromol/L PAF, 2 microg/mL collagen and 15 micromol/L thrombin receptor activating peptide (TRAP). Overall DS showed inhibition of platelet aggregation, platelet activation, platelet-leucocyte conjugate formation and leucocyte activation in response to all the agonists apart from adrenaline (all p < 0.01). DS showed inhibition of platelet aggregation and leucocyte activation equivalent to cangrelor 100 nmol/L and ASA 100 micromol/L. SME dose-dependently inhibited intracellular calcium mobilization in platelets following stimulation with all the platelet agonists with maximum effective at 0.36 mg/mL (all p < 0.01). When used at 0.18 mg/mL its inhibitory effect was equivalent to cangrelor and ASA. We conclude that DS is a potential inhibitor of both platelet and leucocyte activation.
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PMID:Modulation of platelet and leucocyte function by a Chinese herbal formulation as compared with conventional antiplatelet agents. 1823 35

Clinical presentations of atherothrombotic vascular disease, i.e., acute coronary syndromes, cerebrovascular events and events associated with peripheral arterial disease, are the major causes of mortality and morbidity worldwide. Platelet activation and aggregation play an important role in the progression and clinical presentation of atherothrombotic disease, and antiplatelet therapy improves outcome in patients with atherothrombotic vascular disease. Aspirin has been the cornerstone of antiplatelet therapy for many decades, but in recent years, adenosine diphosphate (ADP) receptor antagonists, mainly clopidogrel and ticlopidine, and glycoprotein (GP) IIb/IIIa (integrin alpha IIb beta 3) inhibitors have also shown similar effectiveness. This review briefly summarizes the major clinical trials and recommendations for the efficacy and safety of antiplatelet therapy in patients with established atherothrombotic disease.
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PMID:Acute and long-term antiplatelet therapy. 1854 36

Abstract Aspirin is one of the most widely prescribed drugs for the prevention of thrombosis in patients with vascular disease. Yet, aspirin is unable to prevent thrombosis in all patients. The term "aspirin resistance" has been used to broadly define the failure of aspirin to prevent a thrombotic event. Whether this is directly related to aspirin itself through biochemical aspirin resistance or treatment failure, or if it is because of aspirin's inability to overcome the thrombogenic aspects of the disease process itself, has not been elucidated. This can have dramatic clinical implications for a variety of vascular disease subsets and is cause for concern, considering the high prevalence of aspirin use for both primary and secondary prevention. Disparities exist in the rates of aspirin resistance among certain patient populations, such as women, patients with diabetes mellitus, and those with heart failure, and across clinical conditions, such as cardiovascular and cerebrovascular disease. Clinical trial data from studies observing resistance have revealed that regardless of study size, dose of aspirin, control for drug interactions and adherence, or assay used to measure platelet function, aspirin resistance is associated with an increased risk for adverse events. Although the evidence is mounting, there has yet to be a consensus on the appropriate clinical response to aspirin resistance.
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PMID:Aspirin resistance: disparities and clinical implications. 1865 17

Amyloid-beta (Abeta) cerebral amyloid angiopathy (CAA) affects most Alzheimer's disease (AD) patients and ~30% of otherwise-normal elderly people. APOE epsilon 4 is a major risk factor for CAA in AD. Neurons are probably the source of the vascular Abeta. CAA develops when Abeta is deposited in the vessel walls along or across which it normally passes into the CSF and bloodstream. Vascular deposition is facilitated by factors that increase Abeta40:Abeta42, impede perivascular passage of Abeta or raise its concentration. The levels of some Abeta-degrading enzymes are reduced in AD patients with CAA. However, angiotensin-converting enzyme activity is increased and may act via angiotensin II to increase transforming growth factor beta1, a potent inducer of ECM synthesis. CAA is a cause of intracerebral haemorrhage and cerebral ischaemic damage. In AD, neuritic degeneration is accentuated around Abeta-laden vessels. Rarely, CAA is associated with angiitis. The balance between parenchymal and cerebrovascular degradation of Abeta, and regulation of perivascular extracellular matrix production, are likely to be key determinants of Abeta distribution and pathogenicity within the brain.
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PMID:Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. 1927 89

Aspirin is a unique nonsteroidal anti-inflammatory drug; at high doses (aspirin(high), 1g), it is anti-inflammatory stemming from the inhibition of cyclooxygenase and proinflammatory signaling pathways including NF-kappaB, but is cardioprotective at lower doses (aspirin(low), 75 mg). The latter arises from the inhibition of thromboxane (Tx) B(2), a prothrombotic eicosanoid also implicated in polymorphonuclear leukocyte trafficking. As a result, aspirin(low) is widely used as a primary and secondary preventative against vascular disease. Despite this and its ability to synthesize proresolution 15-epi-lipoxin A(4) it is not known whether aspirin(low) is anti-inflammatory in humans. To address this, we generated skin blisters by topically applying cantharidin on the forearm of healthy male volunteers, causing an acute inflammatory response including dermal edema formation and leukocyte trafficking. Although not affecting blister fluid volume, aspirin(low) (75 mg, oral, once daily/10 days) reduced polymorphonuclear leukocyte and macrophage accumulation independent of NF-kappaB-regulated gene expression and inhibition of conventional prostanoids. However, aspirin(low) triggered 15-epi-lipoxin A(4) synthesis and up-regulated its receptor (FPRL1, ALX). From complimentary in vitro experiments, we propose that 15-epi-lipoxin A(4) exerts its protective effects by triggering antiadhesive NO, thereby dampening leukocyte/endothelial cell interaction and subsequent extravascular leukocyte migration. Since similar findings were obtained from murine zymosan-induced peritonitis, we suggest that aspirin(low) possesses the ability to inhibit mammalian innate immune-mediated responses. This highlights 15-epi-lipoxin A(4) as a novel anti-inflammatory working through a defined receptor and suggests that mimicking its mode of action represents a new approach to treating inflammation-driven diseases.
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PMID:Effects of low-dose aspirin on acute inflammatory responses in humans. 1959 2


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