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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary thrombolysis with streptokinase or tissue plasminogen activator is useful for the treatment of acute myocardial infarction in selected patients. This treatment is associated with local hemorrhagic complications and age-related cerebral hemorrhage. Coronary thrombolysis is contraindicated in patients with transient cerebral ischemia and stroke, arterial hypertension, cerebral trauma, cerebral aneurysms, and arteriovenous malformations, because of the risk of cerebral hemorrhage. We report the occurrence of a cerebral hemorrhage related to cerebral amyloid angiopathy in a patient who underwent thrombolysis and treatment with heparin for acute myocardial infarction. Despite normal coagulation parameters, the cerebral hematoma enlarged over 36 hours, as documented by sequential computed tomographic scans, to produce significant mass effect, which prompted surgical evacuation. Histological examination of the resected specimen demonstrated the strong affinity for Congo red and yellow-green birefringence that are characteristic of cerebral amyloid angiopathy. Hemostasis was difficult to achieve, as the divided or disrupted amyloid-laden cortical vessels failed to vasoconstrict, their contractile elements replaced by amyloid beta protein. The patient died of recurrent myocardial ischemia 3 days postoperatively. The incidence of cerebral amyloid angiopathy increases with advancing age. It must be considered as a potential source of cerebral hemorrhage in elderly patients undergoing thrombolysis for cardiac ischemia. Such an occurrence presents a difficult challenge because cardiac function is compromised, the coagulation profile may be altered, the cerebral hematoma is life threatening, and intracranial hemostasis is difficult to achieve.
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PMID:Cerebral hemorrhage from amyloid angiopathy and coronary thrombolysis. 140 40

In cerebral amyloid angiopathy, the contractile elements of the leptomeningeal and cortical arteries are replaced by noncontractile amyloid beta protein. The incidence of amyloid angiopathy increases with advancing age. It is associated with Alzheimer's disease and spontaneous cerebral hemorrhage. The latter can have the characteristic acute computed tomographic appearance of a hematoma at the cortex-white matter junction with extension of blood into the subarachnoid, subdural, and intraventricular spaces. Multiple hemorrhages are frequent. Additional bleeding can occur after evacuation of the hematoma, and postoperative hemorrhage can occur after cortical biopsy. To elucidate the role of surgery in this condition, we have reviewed 20 consecutive operated cases of cerebral amyloid angiopathy. A first group of 8 patients with senila dementia underwent cortical biopsy without resultant hemorrhage. A second group of 6 patients in good clinical condition had delayed evacuation of a spontaneous cerebral hematoma from cerebral amyloid angiopathy because of the radiological misdiagnosis of a hemorrhage within a tumor. One patient died of a pulmonary embolism, and another had subsequent multiple hemorrhages that were ultimately fatal. A third group of 6 patients in poor neurological condition had the acute evacuation of a spontaneous cerebral hematoma to relieve intracranial hypertension. All died or were severely disabled. One had repeated hemorrhages which added a progressively more severe organic dementia onto an initial hemiplegia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Surgical considerations in cerebral amyloid angiopathy. 196 1

Deposits of amyloid beta-peptide (A beta) in senile plaques and cerebral blood vessels is the prominent feature of Alzheimer's disease (AD), regardless of genetic predisposition. The cellular origin of cerebral deposits of A beta or its precise role in the neurodegenerative process has not been established. Recently we demonstrated a novel action of beta-amyloid on blood vessels--vasoactivity and endothelial damage through superoxide radicals. Since endothelial dysfunction is associated with vascular degenerative diseases, we examined the direct action of A beta on endothelial cells in culture. Cells treated with A beta displayed characteristics of necrotic cell death which was prevented by the free radical scavenging enzyme superoxide dismutase. Stimulation of endothelial nitric oxide (NO) production by the calcium ionophore, A23187, or bradykinin was inhibited by beta-amyloid. We conclude that an imbalance of NO and oxygen radicals may mediate the A beta-induced endothelial damage on endothelial cells in culture and may also contribute to a variety of pathophysiological conditions associated with aging: hypertension, cerebral ischemia, vasospasm, or stroke.
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PMID:beta-amyloid-induced endothelial necrosis and inhibition of nitric oxide production. 902 96

Lacunar brain infarcts and cerebral white matter lesions are frequently observed on magnetic resonance imaging scans in elderly subjects. These lesions are also frequent in patient with cerebral amyloid angiopathy. We examined whether plasma amyloid beta peptide (Abeta) levels are associated with lacunar infarcts and white matter lesions in the general population, and whether the apolipoprotein E (APOE) genotype modifies these associations. We studied 1,077 participants within the population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia. Cross-sectional associations were analyzed by regression models with adjustments for age, sex, creatinine levels, and hypertension. In APOE epsilon4 carriers, plasma Abeta levels were positively associated with lacunar infarcts and white matter lesions, whereas in noncarriers no associations were observed. Per standard deviation increase in Abeta(1-40) and Abeta(1-42) levels the odds ratios for lacunar infarcts were 1.72 (95% confidence interval [CI] = 1.22-2.43) and 1.93 (95% CI = 1.31-2.85), the periventricular white matter lesion grade increased by 0.32 (95% CI = 0.08-0.57) and 0.29 (95% CI = 0.00-0.57), and the subcortical white matter lesion volume increased by 0.48 ml (95% CI = 0.04-0.91) and 0.24 ml (95% CI = -0.27-0.75). Higher Abeta levels are associated with more lacunar infarcts and white matter lesions in elderly subjects who carry an APOE epsilon4 allele.
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PMID:Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions. 1504 97

The major neuropathological lesions defining Alzheimer's disease (AD) include neurofibrillary tangles and amyloid plaques, which are mainly composed of abnormally phosphorylated tau and amyloid-beta (A beta), respectively. Numerous neuropathological and neuroimaging studies indicate that at least one-third of AD cases are complicated by some degree of vascular pathology, whereas in a similar proportion of patients clinically diagnosed with vascular dementia, AD pathology is also present. Many classical vascular risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia have recently been shown also to increase the risk of AD. Growing evidence suggests that vascular pathology lowers the threshold for the clinical presentation of dementia at a given level of AD-related pathology and potentially directly promotes AD lesions such as A beta plaques. Cerebral ischemia, chronically up-regulates expression of the amyloid precursor protein (APP), which is the precursor to the amyloid beta peptide and damages the blood-brain barrier (BBB), affecting A beta peptide clearance from the brain. Recognition of the importance of these vascular risk factors for AD-related dementia and their treatment will be beneficial not only for preventing cardiac, cerebral, and peripheral complications of vascular disease, but also will likely have a direct impact on the occurrence of sporadic AD in older subjects. In this paper, we review some of the links between vascular risk factors and AD pathology and present data on the direct effect of ischemia on cognitive function and A beta deposition in a mouse model of AD.
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PMID:Links between the pathology of Alzheimer's disease and vascular dementia. 1517 82

Vascular involvement in Alzheimer disease (AD) is not necessarily coincident. Current evidence suggests the neuropathology of Alzheimer type of dementia comprises more than amyloid plaques and neurofibrillary tangles. At least a third of recognized AD cases may exhibit cerebrovascular pathology, which also constitutes distinct small vessel disease. Cerebral amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth muscle cells, basal lamina alterations, hyalinosis, and fibrosis are frequently evident in AD. These changes may be accompanied by perivascular denervation that is causal in the cognitive decline of AD. In addition, amyloid beta protein appears directly involved in the degeneration of both the larger perforating arterial vessels as well as cerebral capillaries, which represent the blood-brain barrier. The cerebrovascular pathology in AD also encompasses macro- and micro-infarctions, hemorrhages, lacunas, and ischemic white-matter changes. An interaction of both perivascular mediators and derived factors would perturb the brain vasculature. Peripheral vascular factors such as long-standing hypertension, atrial fibrillation, coronary or carotid artery disease, and diabetes mellitus are also apparent in AD. These factors would modify the cerebral circulation such that a sustained hypoperfusion or oligemia is impacted upon the aging processes to induce the characteristic pathology.
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PMID:Vascular factors in Alzheimer's disease. 1619 Dec 16

The receptor for advanced glycation end products (RAGE) is a cell-bound receptor of the immunoglobulin superfamily which may be activated by a variety of proinflammatory ligands including advanced glycoxidation end products, S100/calgranulins, high mobility group box 1, and amyloid beta-peptide. RAGE has a secretory splice isoform, soluble RAGE (sRAGE), that lacks the transmembrane domain and therefore circulates in plasma. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. Clinical studies have recently shown that higher plasma levels of sRAGE are associated with a reduced risk of coronary artery disease, hypertension, the metabolic syndrome, arthritis and Alzheimer's disease. Increasing the production of plasma sRAGE is therefore considered to be a promising therapeutic target that has the potential to prevent vascular damage and neurodegeneration. This review presents the state of the art in the use of sRAGE as a disease marker and discusses the therapeutic potential of targeting sRAGE for the treatment of inflammation-related diseases such as atherosclerosis, arthritis and Alzheimer's disease.
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PMID:Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target. 1684 91

Amyloid containing senile plaques (SP) and neurofibrillary tangles (NFT) are histologic hallmarks of Alzheimer's disease (AD). Interestingly the SP and NFT found in non-demented, age-matched individuals with ischemic heart disease and/or hypertension are morphologically and topographically identical to those in AD. Cholesterol plays a significant role in production and accumulation of amyloid beta (Abeta) and progression of AD. Cholesterol is also a major contributor in atherosclerotic changes and cardiovascular disease. Numerous studies acknowledged benefits of cholesterol-lowering statins in slowing down the progression of AD, improving cognitive status and significantly reducing risk of cardiovascular events. Accumulating evidence suggests that there is a chronic inflammatory reaction in the areas of the brain affected by AD and C-reactive protein (CRP) is identified as a key molecule of acute phase of inflammation. CRP is also a very sensitive marker for cardiovascular events and excellent prognostic tool in post-heart attack and post-coronary artery bypass surgery recovery. Here we report that cholesterol lowering with atorvastatin produces no significant change in CRP levels in treating AD patients who participated in ADCLT (AD cholesterol lowering trial).
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PMID:Change in circulating C-reactive protein is not associated with atorvastatin treatment in Alzheimer's disease. 1694 13

Findings from longitudinal and cross-sectional studies suggest an association between high blood pressure and dementia, and in turn the use of antihypertensives has been suggested to reduce incidence of dementia. Alzheimer's disease, the most common cause of dementia, is characterised in part by the deposition of amyloid beta protein (Abeta) in the brain. Reduction of Abeta load is now a major therapeutic strategy. In recent years the renin-angiotensin system, already of recognised importance in the pathogenesis of hypertension, has become a source of interest in the pathogenesis of Alzheimer's disease. This review explores molecular, genetic, and clinical studies that might help explain the relation between the renin-angiotensin system, hypertension, and Alzheimer's disease and whether treatment with angiotensin converting enzyme (ACE) inhibitors and similar treatment strategies have a part to play in the management of the disease.
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PMID:Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease? 1736 41

Several factors have been implicated in Alzheimer's disease (AD) but there is no definite conclusion as to the main pathogenic agents. Mutations in the amyloid precursor protein (APP) that lead to increased production of amyloid beta peptide (A beta) are associated with the early-onset, familial forms of AD. However, in addition to ageing, the most common risk factors for the sporadic, prevalent form of AD are hypertension, hypercholesterolaemia, ischaemic stroke, the ApoE4 allele and diabetes, all characterized by a vascular pathology. In AD, the vascular pathology includes accumulation of A beta in the vessel wall, vascular fibrosis, and other ultrastructural changes in constituent endothelial and smooth muscle cells. Moreover, the ensuing chronic cerebral hypoperfusion has been proposed as a determinant factor in the accompanying cognitive deficits. In transgenic mice that overexpress mutated forms of the human APP (APP mice), the increased production of A beta results in vascular oxidative stress and loss of vasodilatory function. The culprit molecule, superoxide, triggers the synthesis of other reactive oxygen species and the sequestration of nitric oxide (NO), thus impairing resting cerebrovascular tone and NO-dependent dilatations. The A beta-induced cerebrovascular dysfunction can be completely abrogated in aged APP mice with antioxidant therapy. In contrast, in mice that overproduce an active form of the cytokine transforming growth factor-beta1 and recapitulate the vascular structural changes seen in AD, antioxidants have no beneficial effect on the accompanying cerebrovascular deficits. This review discusses the beneficial role and limitations of antioxidant therapy in AD cerebrovascular pathology.
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PMID:Oxidative stress and cerebrovascular dysfunction in mouse models of Alzheimer's disease. 1791 59


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