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)

Besides the optimal management of risk factors for stroke and carotid surgery, antiplatelet agents are the cornerstone for prevention of cerebral ischaemia. The aim of this overview is to determine their role in the prevention of cerebral ischaemia, from available literature. In primary prevention, the benefit of aspirin has been established only for patients with non-valvular atrial fibrillation and a low risk of cardioembolism, or as an alternative choice of warfarin, and in subjects at high risk of atherosclerosis. In secondary prevention, antiplatelet agents are effective to reduce the risk in patients with ischaemic stroke due to atherosclerosis: aspirin (50 to 1300 mg), ticlopidine (500 mg), clopidogrel (75 mg) and dipyridamole (400 mg) are effective, but the higher levels of risk reduction are obtained with clopidogrel, ticlopidine and the association aspirin--dipyridamole. Aspirin is recommended in most other causes of cerebral ischaemia, except in high risk cardiopathies when anticoagulation is possible. Other domains should still be explored: are antiplatelet agents also effective to reduce the risk of cerebral ischaemia in patients with other causes, especially lipohyalinosis of the deep perforators leading to lacunar infarcts? In daily practice, does prescription follow recommendations? Will it be possible to reproduce the results of the European Stroke Prevention Study (ESPS)2? Are antiplatelet agents other than aspirin effective in non-valvular atrial fibrillation? Are other associations of antiplatelet agents more effective than these agents alone? Finally, what will be the role of new antiplatelet agents in the future?
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PMID:[Prevention of cerebral ischemia: anti-platelet agents]. 1052 50

A 47-year-old man developed progressive muscular weakness in the left arm. MR images revealed low intensity signal lesions with ring enhancement by Gd-DTPA in right fronto-parietal lobes. At that time cerebral angiography was not performed because he refused. A tuberculin skin test showed strongly positive reaction and then administration of anti-tuberculous drugs was started. His symptom had remained stable for one year, but left facial palsy and dysarthria added about two years later. MR images revealed expansion of the lesions in right parietal lobe, adding cortical high intensity signal lesions with Gd-DTPA enhancement on T1-weighted images. Angiography disclosed tubular stenosis of right internal carotid artery at the portion of cervical to petrous segment and the local stenosis at right renal artery. These lesions were considered to be caused by fibromuscular dysplasia, but not atherosclerosis, because we could not find any atherosclerotic lesions in other arteries including right carotid bifurcation. His manifesting symptoms were ascribed to slowly progressive cerebral ischemia. And peculiar MRI findings in his early stage resembled those of inflammatory granulomatous diseases.
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PMID:[A peculiar MRI findings in a case with slowly progressive cerebral ischemia caused by internal carotid artery stenosis possibly due to fibromuscular dysplasia]. 1065 64

Nitric oxide (NO) and its reactant product, peroxynitrite, have been implied to mediate neuronal damage following cerebral ischemia. However, the cellular targets of these compounds remain unclear. Studies using poly(ADP-ribose) polymerase (PARP) inhibitors and PARP knock-out mice have recently demonstrated that excessive activation of this nuclear enzyme plays an important role in NO-induced neurotoxicity. To evaluate the relevance of this plausible candidate gene to human stroke, we undertook a case-control study in Japanese. Participants comprised 213 cerebral infarction cases and 374 age- and sex-matched controls. As a primary investigation, we screened polymorphic sites of the PARP gene, and newly identified a total of four polymorphisms in 1230-bp 5'-flanking sequence. None of them were, however, located on the known promoter components of the gene. Two bi-allelic polymorphisms selected and a CA-repeat polymorphism were subsequently characterized in the case-control study, but none were significantly associated with cerebral infarction in the present study. Our data thus suggest that the tested PARP polymorphisms do not principally contribute to cerebral infarction, although extensive searches would be required to clarify whether the PARP gene plays an important role in the pathogenesis of human stroke.
Atherosclerosis 2000 Feb
PMID:Evaluation of the poly(ADP-ribose) polymerase gene in human stroke. 1065 71

Cerebral white matter lesions, such as leukoaraiosis, may be a result of damage from cerebral ischaemia, and may also be associated with the degenerative process in Alzheimer's disease. The apolipoprotein epsilon4 (apoepsilon4) genotype is a genetic risk factor for both Alzheimer's disease and ischaemic brain damage through acceleration of atherosclerosis. The aim was to determine whether apoepsilon4 may be related to the formation of cerebral white matter lesions in Alzheimer's disease. The association of apoE genotype, sex, age, and the presence of several vascular risk factors, with the presence of white matter lesions in 55 patients clinically diagnosed with Alzheimer's disease was investigated. The cerebral white matter lesions were identified by T2 weighted MRI and classified on a 4 grade scale from no lesion to diffuse lesion. The odds ratio (OR) of the factors mentioned above to the presence of white matter lesions was determined and tested by Fisher's exact test. The association of the lesion grades with these factors was analysed by non-parametric tests. The apoE 4 genotype was strongly associated with Alzheimer's disease (p=0.0001), but not associated with the presence or the degree of cerebral white matter lesions in Alzheimer's disease (OR=1.09, p>0.99). Aging (>70 years old) was a significant risk factor for white matter lesions (OR=7.2, p=0.0006) and age was significantly correlated with the lesion (p=0.0075). The OR of female sex to the lesion grades was 2.89 (p=0.084) and the lesion grade of female sex was significantly higher than that of the male sex (p=0.047). Other vascular risk factors were not significantly associated with the presence of white matter lesions. These findings suggest that there is a sex difference in white matter pathology in Alzheimer's disease.
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PMID:Cerebral white matter lesions are not associated with apoE genotype but with age and female sex in Alzheimer's disease. 1076 1

Atherosclerosis of carotid artery, resulting in stenosis is a common cause of cerebral ischaemia. Ischaemic stroke is cause of death in 10% of patients and the leading cause of disability in adults. The risk of stroke increases with the degree of stenosis. The diagnosis of the degree of stenosis is performed by duplex sonography, MR-angiography, CT-angiography and conventional angiography. Carotid endarterectomy is a method of choice in the treatment in the case of high-grade carotid stenosis. The operation was introduced in 1953. Either regional or general anaesthesia is used for the operation. The different monitoring techniques are used for assessment of the need for shunting. Microsurgical technique enables perfect endarterectomy and fine arterial repair without need for patch grafting. Other techniques of the treatment for carotid stenosis, including carotid angioplasty with or without stenting are subject to the evaluation. Carotid endarterectomy is now the method of choice in the treatment of high-grade carotid stenosis.
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PMID:[Advances in carotid endarterectomy--review]. 1080 63

The Alzheimer type of dementia and stroke are known to increase at comparable rates with age. Recent advances suggest that vascular risk factors linked to cerebrovascular disease and stroke in the elderly significantly increase the risk of developing Alzheimer's disease (AD). These include atherosclerosis, atrial fibrillation, coronary artery disease, hypertension, and diabetes mellitus. Moreover, review of various autopsy series shows that 60-90% of AD cases exhibit variable cerebrovascular pathology. Although some vascular lesions such as cerebral amyloid angiopathy, endothelial degeneration, and periventricular white matter lesions are evident in most cases of AD, a third will exhibit cerebral infarction. Despite the interpretation of pathological evidence, longitudinal clinical studies suggest that the co-existence of stroke and AD occurs more than by chance alone. Strokes known to occur in patients with Alzheimer syndrome and most frequently in the oldest old substantially worsen cognitive decline and outcome, implicating some interaction between the disorders. Nevertheless, the nature of a true relationship between the two disorders seems little explored. What predisposes to strokes in underlying cognitive decline or AD? Is it possible that cerebral ischemia is a causal factor for AD? I examined several vascular factors and the vascular pathophysiology implicated in stroke and AD, and propose that cerebral ischemia or oligemia may promote Alzheimer type of changes in the aging brain. Irrespective of the ultimate pathogenetic mechanism, these approaches implicate that management of peripheral vascular disease is important in the treatment or prevention of Alzheimer's disease or mixed dementia.
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PMID:The role of cerebral ischemia in Alzheimer's disease. 1086 17

The estimated risk of development of complications of atherosclerosis (coronary or cerebral ischaemia) is one of the activities every physician should include in the diagnostic and therapeutic algorithm. Treatment with hypolipidaemic agents is indicated according to the European consensus if the danger of a coronary or cerebral event is 20%/10 years. The objective of preventive provisions should be reduction of this risk to < 5%/10 years in younger subjects (< 45 years in men and < 50 years in women) and < 10%/10 years in elderly subjects. These recommendations obviously do not apply to secondary prevention (in case of complications of atherosclerosis) where treatment with hypolipidaemic agents is indicated already when the LDL-cholesterol level is 2.3 mmol/l or when triacylglycerols are 2.3 mmol/l, combined with a drop of HDL-cholesterol to < 0.9 mmol/l.
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PMID:[Assessment of risk for the development of manifest atherosclerosis and indications for hypolipidemic therapy (global risk assessment)]. 1104 54

Arterioarterial thromboembolism from extracranial internal carotid artery (ICA) stenosis is an important pathogenic mechanism of ischemic stroke. However, even a high-grade ICA stenosis carries a greatly variable annual risk of stroke, as high as 13% following a recent occurrence of transient or minor cerebral ischemia or as low as 1-2% in clinically asymptomatic patients. There is increasing evidence that inflammatory processes play a central role in atherosclerosis and particularly in plaque destabilization converting chronic atherosclerosis into an acute neurological disorder. In thromboendarterectomy specimens from patients with high-grade ICA stenoses, the extent of inflammatory infiltration and the expression of matrixmetalloproteinase-9 correlated to clinical and ultrasonic features of plaque destabilization such as cerebral microembolism. Inflammation might become a new therapeutic target in symptomatic carotid artery disease.
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PMID:[Unstable carotid stenosis--an inflammatory disease?]. 1113 91

Atherosclerosis involves structural change to the intima and media of medium- and large-sized arteries. Although an atherosclerotic plaque may remain clinically silent, it is prone to disruption, leading to local platelet activation and aggregation. Therefore, the major complication of atherosclerosis is thrombosis, with local occlusion or distal embolism - a generalized disease process known as atherothrombosis. The three main clinical manifestations of atherothrombosis are coronary heart disease (myocardial infarction and angina), peripheral arterial disease and cerebral ischaemia. Atherothrombosis is a leading cause of mortality, and stroke is the leading cause of disability in adults, the second most important cause of dementia and the third most common cause of death in Western countries. Ischaemic stroke accounts for 80% of strokes and atherothrombosis accounts for approximately 20% of all strokes. Criteria for atherothrombotic stroke are evidence of a 50% (or greater) stenosis of a cervical artery and exclusion of other potential causes. The incidence of cerebrovascular events is 2,900 per million inhabitants per year, consisting of 500 transient ischaemic attacks and 2,400 strokes, of which 75% are first-ever stroke. The prevalence of stroke in the same population is 12,000, of which 800 patients (7%) per year have recurrences. The risk of ipsilateral stroke is 5% per year and the risk of a cardiac event is higher at 7%. Besides optimal management of risk factors for atherothrombosis and carotid surgery, antiplatelet therapy is the cornerstone of vascular prevention. In secondary prevention, antiplatelet agents are effective in reducing the risk of further ischaemic events in patients with atherothrombosis. Clopidogrel, a newly licensed ADP receptor antagonist, is the only antiplatelet agent to have demonstrated its superiority versus aspirin for the reduction of major ischaemic events (myocardial infarction, ischaemic stroke, vascular death) in patients whose initial manifestation of atherothrombosis was one of the three main clinical manifestations of the disease (recent ischaemic stroke, myocardial infarction, established peripheral arterial disease).
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PMID:Atherothrombosis: a major health burden. 1131 15

The diseases of vessels, mainly of those in brain are one of the most serious problems of the medical practice. The encephalomalacia or cerebral infarctions are usually caused by transient or permanent obstruction of the brain arteries lumen. Beside local dysfunction of vessels the obstructions could be based on embolic events originating in the heart. Such an obstructions are resulting in global and focal cerebral ischaemias. Arterial occlusion results in cerebral ischaemia and the lack of oxygen (anoxia) which leads to reversible or irreversible injury of the nervous cells in the ischaemic region. The local cell injury or cell death causes attraction of macrophages invading into the devitalized tissue within 72-96 hours after the beginning of the ischaemia. The aim of this study was to find out the correlation between asymptomatic or symptomatic course regarding localisation of the ischaemic lesions in the cerebral tissue. Our anatomical findings were collected from 318 autopsies, and reports on postmortem examinations during the period between September-December 1998. The grossing of the brain was carried out by using of Virchow's method. Atherosclerosis, hypertension, and diabetes mellitus were found to be the main risk factors for the production of focal cerebral ischaemia. Of those patients with focal cerebral ischaemia atherosclerosis had 87.5%, 44.3% were suffering from hypertension, and 25% from diabetes mellitus. The focal ischaemia analysed in this study originated from arterial stenosis or thromboembolic obstructions. We divided the lesions into 3 groups according to their size. The most frequently apparent lesions (72%) were the small cysts (0-10 mm in diameter)-lacunae. The majority of them (90%) was found in the basal ganglia. The second group consisted of postmalatic pseudocysts (10-30 mm in diameter), and the third group was represented by encephalomalatic lesions which were larger than 30 mm. Cerebral ischaemic lesions were present in 27.8% of the studied cases. Nevertheless, more than the half (56.8%) of the affected brains (postmalatic pseudocysts, lacunae and malaciae) belongs to the group of patients who were clinically asymptomatic. The asymptomatic lesions, having negative results in the patient's history, and the clinical course were localised mainly in the basal ganglia of both sides and in the frontal part of the right (nondominant) hemisphere.
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PMID:[Morphologic and clinical sequelae of focal ischemic lesions]. 1137 5


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