Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CAA is the infiltration of leptomeningeal and penetrating cortical vessels with amyloid, sparing the subcortical regions and the systemic vasculature. It occurs with increasing frequency after the sixth decade. The major clinical manifestation of CAA is lobar intracerebral hemorrhage, which can be sporadic or hereditary. CAA has also been associated with normal aging, Alzheimer's disease, cerebral infarction, and periventricular demyelination. Biochemical studies have shown that the amyloid deposits in the brains of patients with normal aging, sporadic CAA-associated hemorrhage, hereditary cerebral hemorrhage, and Alzheimer's disease are identical. The exact mechanism by which CAA produces lobar hemorrhages and the role of CAA in the development of dementia are unclear. Biopsy of the involved cerebral cortex and leptomeninges is the only definitive way to diagnose CAA. Acute management of CAA-associated lobar hemorrhage consists of aggressive control of associated hypertension and supportive care. Surgical removal of the hemorrhage has not been shown to improve survival. Antiplatelet and anticoagulant therapy should be avoided in elderly patients with known CAA.
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PMID:Diagnosis and treatment of cerebral amyloid angiopathy. 186 14

The goals in the treatment of hypertension have been outlined previously. The antihypertensive drugs should achieve as many of these criteria as possible. 1. Efficacious as monotherapy in more than 50% of all patients (demographics) 2. 24-hour blood pressure control during all activities 3. Once per day dosing 4. Hemodynamically logical and effective: reduces SVR, improves arterial compliance, preserves CO and maintains perfusion to all vital organs 5. Lack of tolerance or pseudotolerance: no reflex volume retention or stimulations of neurohumoral mechanisms 6. Favorable biochemical and metabolic effects 7. Reverses the structural, vascular smooth muscle, cardiac hypertrophy, LVH, and improves systemic and diastolic compliance, LV contractility and function, and reduces ventricular ectopy if present 8. Reduces all end-organ damage: cardiac, cerebrovascular, renal, retinal and large artery 9. Maintains normal hemodynamic response to aerobic and anerobic exercise 10. Low incidence of side effects and good quality of life 11. Good compliance with drug regimen 12. Good profile in concomitant diseases or problems The drugs that come closest to these characteristics include CCB, ACEI, CAA, and alpha blockers. All of these agents are effective as monotherapy and should be given as initial therapy to the maximum dose shown in Table 10 or until the advent of side effects, whichever occurs first. Combination therapy should be the next step, using the principal of go low, go slow, using additive or synergistic drug combinations. Therapy should be individualized using the subsets of hypertension approach: Diuretics in particular, especially high-dose diuretics, and BB to a lesser extent, should be reserved as second- or third-line drugs and used for specific indications and in the lowest dose possible to achieve clinical results. For example, diuretics would be reserved for volume overload states, systolic CHF, and volume-resistant hypertension. Beta blockers would be reserved for patients after a Q-wave myocardial infarction, those with obstructive angina, specific cardiac arrhythmias, and other like conditions. Long-term, prospective, clinical trials will be needed to confirm that CCB, ACEI, CAA, and alpha blockers reduce end-organ damage more effectively than diuretics, BB, direct vasodilators, and older antihypertensive drugs. Until then, one must rely on scientific evidence, discussed here, that strongly suggests that reduction in risk factors for end-organ damage will reduce the end-organ damage in heart, brain, kidney, and large arteries.
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PMID:Hypertension strategies for therapeutic intervention and prevention of end-organ damage. 194 95

Patients with bioptically ascertained glomerulonephritis of the years 1969-1981 were examined. At the time of the kidney biopsy etiology, onset of the disease and data of the findings were evaluated. Moreover, in 160 out of 300 patients after-examinations were performed. Especially also the examination of patients with erythrocyturia was carried out with the help of the phase contrast microscopy. In a second part of the examinations which we report on 2 therapy studies were performed. In the first therapy study the effectiveness of the therapy with prednisolone (n = 33), prednisolone + cytostatic drug (n = 43) as well as the indomethacin treatment (n = 52) in patients with and without nephrotic syndrome was examined. We found that an initial prednisolone dose of more than 50 mg/die for at least over 1 month is more successful than a low prednisolone dose. Indomethacin has no clinically provable therapeutic effect in the nephrotic syndrome. In normal renal function the duration of the disease has no ascertained influence on the results of the therapy. In the second therapy study the effectiveness of the CAA- (n = 27) and the CAAP-therapy, respectively, (n = 98) (cytostatic drugs, anticoagulant drugs, thrombocyte aggregation inhibitors and prednisolone) was investigated. The results of the therapy depending upon the clinical course and the morphological findings revealed that there is an indication to the CAA-CAAP-therapy in nephrotic syndromes in glomerulonephritis with and without sclerosation as well as in glomerulonephritis with relapsing exacerbations with and without sclerosations. No indication for this therapy is given in chronic courses of glomerulonephritis with slight proteinuria and in nephrotic syndromes with hypertension.
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PMID:[Diagnosis and therapy of chronic glomerulonephritis in long-term follow-up]. 370 78

Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.
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PMID:Resistance to activated protein C and Legg-Perthes disease. 1037 32

Amyloid-beta (A beta) deposition in cerebral vessels (cerebral amyloid angiopathy, CAA) is accompanied by degeneration of vascular cells, including pericytes and smooth muscle cells. Previous studies indicated that specific A beta protein isoforms are toxic for cultured human brain pericytes and smooth muscle cells. In particular, A beta 1-40 carrying the E22Q mutation, as in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), is toxic. We investigated the effects of the A beta-binding protein apolipoprotein E (ApoE) on the toxicity of A beta for cultured human brain pericytes. We compared the toxicity of HCHWA-D A beta 1-40 for pericyte cultures with different ApoE genotypes, studied the accumulation of A beta and ApoE in these different cell cultures, and investigated the effects of exogenous ApoE. Pericyte cultures with an ApoE epsilon 2/epsilon 3 genotype were more resistant to HCHWA-D A beta 1-40 treatment than cultures with a epsilon 3/epsilon 3 or epsilon 3/epsilon 4 genotype. Cell death was highest in cultures homozygous for ApoE epsilon 4. The extent to which both A beta ApoE accumulated at the cell surface was parallel to the degree of toxicity. The addition of purified ApoE resulted in a decrease in cell death. These data suggest that ApoE4 may direct A beta more efficiently than other ApoE isoforms into a pathological interaction with the HBP cell surface. The results of this study are in line with the observations that inheritance of the ApoE epsilon 4 allele increases the risk of developing Alzheimer's disease, and that the ApoE epsilon 2 allele has a relatively protective effect.
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PMID:Amyloid-beta-induced degeneration of human brain pericytes is dependent on the apolipoprotein E genotype. 1081 7

Cerebral amyloid angiopathy frequently causes recurrent intracerebral hemorrhages in elderly patients who do not have systemic hypertension. Surgery should be reserved for conditions which cannot be controlled by medical treatment. When surgery is needed, potential complications (such as bleeding near the operation site or remote area) should be kept in mind. A case study of a 66-year-old woman with cerebral amyloid angiopathy and recurrent intracerebral hemorrhages is presented.
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PMID:Recurrent intracerebral hemorrhages in cerebral amyloid angiopathy: a case report. 1090 72

Cerebral amyloid angiopathy (CAA) is one of the two most common cerebral arteriopathies seen in the brains of elderly patients. The other is arteriosclerosis (AS), historically considered a consequence of chronic hypertension and also described as lipohyalinosis (LH), a clinicopathologic association that is increasingly questioned. These and other less frequently encountered degeneralions of the cerebral microvasculature (CADASIL, Binswanger subcortical leukoencephalopathy) share the common feature of degeneration of the medial smooth muscle layer within arteriolar walls. This can be dramatic in CAA, in the course of which complete replacement of medial smooth muscle by fibrillar amyloid may occur. It is a less prominent feature of CADASIL and BSLE: in the latter condition, medial smooth muscle hyperplasia, possibly a response to some kind of injury, is a more dramatic finding. In some of these "angiomyopathies", fibrinoid necrosis of the arterial wall and microaneurvsm formation may lead to stroke, manifest as cerebral hemorrhage. With CADASIL and BSLE, ischemic brain injury is more common. In the case of CAA, upregulation of the Abeta-amyloid precursor protein occurs when arteriolar smooth muscle cells in culture are exposed to prolonged hypoxia, especially with reoxygenation. Injury to arteriolar smooth muscle cells may be one mechanism by which angiomyopathies progress and become symptomatic.
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PMID:Non-CAA angiopathies and their possible interactions with cerebral amyloid angiopathy. 1167 85

Cerebral amyloid angiopathy (CAA) due to the accumulation of amyloid beta-protein (Abeta) occurs in up to half of elderly individuals and in most cases of Alzheimer's disease (AD). Following identification of the apolipoprotein E (APOE) epsilon4 allele as a risk factor for AD, APOE epsilon4 was also found to be associated with asymptomatic CAA. The major clinical manifestation of CAA is stroke due to a lobar hemorrhage. A complex relationship between APOE epsilon4, APOE epsilon2 and hemorrhage associated with CAA (CAAH) is emerging. Pathological studies have demonstrated that APOE epsilon2 is over-represented among patients with CAAH. This remains the case for patients with co-existing Alzheimer's disease, who otherwise have a very low epsilon2 allele frequency. Other forms of intracranial hemorrhage do not share the same association, indicating that APOE epsilon2 has a specific association with CAAH. Patients with the epsilon2 allele and CAAH are more likely to have taken anticoagulant or antiplatelet medication, had hypertension or had minor head trauma than non-epsilon2 carriers. In addition, the epsilon2 allele is specifically associated with CAA-associated microangiopathic changes such as fibrinoid necrosis and concentric splitting of the vessel wall.
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PMID:APOE gene polymorphism as a risk factor for cerebral amyloid angiopathy-related hemorrhage. 1167 91

Current evidence suggests that the neuropathology of Alzheimer type of dementia comprises more than amyloid plaques and neurofibrillary tangles. At least a third of Alzheimer disease (AD) cases may exhibit significant cerebrovascular pathology, which constitutes distinct small vessel disease (SVD). Cerebral amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth muscle cells, basal lamina alterations, hyalinosis and fibrosis are often evident in AD. These changes may be accompanied by perivascular denervation that is causal in the cognitive decline of AD. Amyloid beta protein may cause degeneration of both the larger perforating arterial vessels as well as cerebral capillaries, which represent the blood-brain barrier. In addition, macro- and microinfarctions, haemorrhages, lacunes and ischaemic white matter changes are also present in AD. The development of SVD in late-onset AD may engage an interaction of perivascular mediators as well as circulation-derived factors that perturb the brain vasculature. Peripheral vascular disease such as long-standing hypertension, atrial fibrillation, coronary or carotid artery disease and diabetes could further modify the cerebral circulation such that a sustained hypoperfusion or oligaemia is impacted upon the ageing brain.
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PMID:Small vessel disease and Alzheimer's dementia: pathological considerations. 1190 Dec 43

Cerebral amyloid angiopathy (CAA), a condition affecting the elderly in a way similar to that of Alzheimer's disease, results from amyloid deposition within small and medium arteries of the cerebral leptomeninges and cerebral cortex. Next to atheromatosis, amyloidosis is the second most frequent cause of cerebral haemorrhage, especially recurrent. The most recent publications suggest that amyloidosis may also cause transient ischaemic attacks (TIA), cerebral infarcts, Binswanger's type leukoencephalopathy, symptoms resembling these of cerebral pseudotumour, and other dysfunctions. A definite diagnosis of cerebral amyloid angiopathy may be determined by autopsy, and sometimes intravital cerebral biopsy is performed. A clinical diagnosis of probable CAA is based on the presence of multiple superficial haemorrhages in the elderly people without hypertension. No CAA treatment methods are known yet. However, to prevent haemorrhages in CAA it is important that anticoagulants and antiplatelet drugs should be avoided in the treatment of cerebral and other ischaemic disorders, because of an increased risk for haemorrhage.
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PMID:[Cerebral amyloid angiopathy as a cause of strokes]. 1455 86


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