Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risks accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions, and cognitive testing among 224 neurologically and cognitively normative aging volunteers. After age 60, cerebral atrophy, ventricular enlargement, polioaraiosis, and leukoaraiosis geometrically increased as perfusions declined. Risks accelerating perfusional decline, cerebral atrophy, polioaraiosis, and leukoaraiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5 +/- 11.9, subtle cognitive decline began, accelerated by TIAs, hypertension, and heart disease. Leukoaraiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with vascular dementias. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with Alzheimer's disease. We concluded that TIAs, hypertension, hyperlipidemia, smoking, and male gender accelerate cerebral degenerative changes, cognitive decline, and dementia.
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PMID:Cardiovascular and other risk factors for Alzheimer's disease and vascular dementia. 1081 32

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.
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PMID:Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese. 1082 Nov 38

Putative risk factors accelerating mild cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT, densitometry, perfusions, and cognitive testing among neurologically and cognitively normative aging volunteers. A total of 224 normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59.5 +/- 15.8 years. Mean follow-up is 5.8 +/- 3.3 years. At follow-up, 22 developed mild cognitive impairment (41 CCSE >/= -3), 19 became demented-8 with Vascular type (VAD), 11 with Alzheimer's type (DAT)-and 183 remain cognitively unchanged. Cerebral atrophy, tissue densities, and perfusions were measured by Xe-CT. After age 60, cerebral atrophy, ventricular enlargement, and polio- and leuko-araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio-araiosis, and leuko-araiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, and male gender. At age 71.5 +/- 11.9, mild cognitive impairment began accelerated by TIAs, hypertension and heart disease. Leuko-araiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with VAD. Excessive cortical perfusional decrease, gray and white matter hypodensities, and cerebral atrophy correlate with cognitive decline.
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PMID:Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia. 1086 1

The very low density lipoprotein receptor (VLDLR) has a potentially important role in lipoprotein metabolism and Alzheimer's disease. We developed amplification primers for most of the coding region and 3'-untranslated region of VLDLR and used sequencing of genomic DNA to examine these regions of VLDLR in subjects with familial combined hyperlipidemia and in normal controls. We identified ten novel single nucleotide polymorphisms (SNPs) for VLDLR. We also found one rare coding sequence variant, S>R153, in a subject with familial combined hyperlipidemia, which was absent from 2360 normal alleles. The identification of intron-exon boundaries, amplification primers, and SNPs provides tools to investigate VLDLR for genetic association and linkage studies.
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PMID:Single nucleotide polymorphisms of the very low density lipoprotein receptor (VLDLR) gene. 1150 49

Hyperhomocysteinemia (HHCY) is a consequence of disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological and clinical studies have proven HHCY to be an independent risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Trials in progress may clarify the "causality" of high homocysteine (HCY) concentrations and will assess the value of HCY lowering therapy. HHCY is also seen as a risk factor for neurodegenerative diseases such as cognitive impairment, dementia, Alzheimer's disease, and also for depression. There is a high prevalence of HHCY as a syndrome of vitamin shortage in elderly subjects, which strongly increases with advancing age. Elderly people have a high frequency of vitamin B12 deficiency which is more reliably diagnosed by measurement of serum methylmalonic acid and holotranscobalamin II, the metabolically active B12 fraction, than by total serum vitamin B12. Subjects who follow a strict vegetarian diet also have a high prevalence of HHCY caused by vitamin B12 deficiency. For prevention of neurological damages an early diagnosis of vitamin B12 deficiency is important. Furthermore, HHCY is a factor in the pathogenesis of neural tube defects and preeclampsia. HCY should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in adipose subjects, in elderly people, in vegetarians, in postmenopausal women, and in early pregnancy.
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PMID:Hyperhomocysteinemia: a new risk factor for degenerative diseases. 1238 6

To elucidate risk factors for cerebral amyloid angiopathy (CAA) in the elderly, we have investigated 201 autopsy cases of elderly Japanese (ages: 62-104 years), including 82 patients with Alzheimer's disease (AD). Severity of CAA showed no relationship with the history of hypertension, hyperlipidemia, or diabetes mellitus, nor with severity of atherosclerosis of cerebral and systemic arteries, indicating that common vascular risk factors would not be related to CAA. Incidence and severity of CAA were significantly higher in the AD cases compared with the non-AD cases (p < 0.0001). Severity of CAA correlated with densities of senile plaques and neurofibrillary tangles in total and non-AD cases, although the correlations were not significant within the AD cases. Associations of genetic polymorphisms with CAA have been investigated for genes of apolipoprotein E (APOE), presenilin 1 (PS1), alpha1-antichymotrypsin (ACT), butyrylcholinesterase, alpha2-macroglobulin, and paraoxonase. Severity of CAA in APOE epsilon4 carriers is significantly higher than that in non-epsilon4 carriers in total cases, although no significant difference was found in the CAA severity between the epsilon4 carriers and non-epsilon4 carriers within the AD or non-AD group. An intronic polymorphism of PS1 was significantly associated with the severity of CAA, indicating that the PS1 2/2 genotype may be related to lower risk of CAA. A polymorphism in the signal peptide sequence of ACT was significantly associated with the CAA severity in the AD group. Our results suggest that CAA shares risk factors with AD and that multiple genetic factors would be associated with the risk of CAA in the elderly.
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PMID:Risk factors for cerebral amyloid angiopathy in the elderly. 1248 Jul 32

Oxidative stress appears to be of fundamental relevance to diseases as diverse as atherosclerosis, cancer, and Alzheimer's disease. Observational data in humans have suggested that antioxidant vitamin intake is associated with reduced cardiovascular disease. Animal studies are largely consistent with the concept that dietary supplementation with antioxidant vitamins reduces the progression of atherosclerosis. However, recent prospective, controlled clinical trials of vitamin E, including the Cardiovascular Disease, Hypertension and Hyperlipidemia, Adult-Onset Diabetes, Obesity, and Stroke (CHAOS) study, the Heart Outcomes Prevention Evaluation (HOPE) trial, Gruppo Italiano per lo Studio della Sopravvivvenza nell'Infarto Miocardico (GISSI)-Prevenzione trial, the Secondary Prevention with Antioxidants of Cardiovascular Disease in End Stage Renal Disease (SPACE) trial, and the Heart Protection Study (HPS) present a confused picture. The various possibilities that have been advanced to explain this discrepancy are discussed in this review. A striking feature of these and other trials of antioxidants is the absence of a biochemical basis for patient inclusion or, indeed, dose selection. Patients with high levels of oxidant stress or depletion of natural antioxidant defense systems may be the most likely to benefit from antioxidant therapy. If this is the case, then reliable, quantitative indices of in vivo oxidant stress such as urinary isoprostane levels should be considered as an inclusion criterion for patient selection. Future trials of antioxidant therapy in cardiovascular disease should then be targeted toward such patients with high levels of oxidant stress or patients with depletion of natural antioxidant defense systems. Furthermore, the dose of antioxidant should be chosen based on a surrogate readout that is a reliable, reproducible, and easily obtainable in vivo measure of oxidant stress. In the interim, although the safety of vitamin E up to doses of 800 IU/day has been determined, the conflicting nature of the results published to date encourages us to avoid making premature recommendations with respect to vitamin E supplementation in the prevention and treatment of cardiovascular disease.
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PMID:Treatment of atherosclerosis in the new millennium: is there a role for vitamin E? 1273 94

It has been assumed that statins work as a preventative drug for Alzheimer's disease (AD). Although some epidemiological observations raise doubts to the effectiveness of statins for AD, many in vitro and clinical studies insist on the effectiveness of statins decreasing amyloid-beta (Abeta) levels in medium or blood. To explore the effect of pravastatin on Abeta production, we followed the longitudinal plasma levels of both Abeta 40 and Abeta 42 during the allocation of pravastatin in 46 patients with hyperlipidemia. We found no correlation between plasma cholesterol levels or the decreasing values of total cholesterol and those of Abeta 40 or Abeta 42. Patients having Apolipoprotein E4 (ApoE4) had higher low-density lipoprotein levels and lower Abeta 40 levels in plasma, suggesting ApoE4 seems to influence plasma Abeta levels via cholesterol metabolism.
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PMID:Pravastatin at 10 mg/day does not decrease plasma levels of either amyloid-beta (Abeta) 40 or Abeta 42 in humans. 1455 Sep 19

Plasma membranes are fluid structures and the maintenance of fluidity is a prerequisite for function, viability, growth and reproduction of cells. Membrane fluidity is the reciprocal of membrane microviscosity, which in turn is inversely proportional to rotational and lateral diffusion rates of membrane components. In the absence of constraints most lipids and unrestrained integral proteins freely diffuse in the plane of the membrane with high diffusion coefficients. The fluid mosaic model of plasma membrane structure is essentially still valid but this model is by its nature a macroscopic one. At present, attention is focused on molecular structural details of protein-lipid interactions and on the static and dynamic structure of membrane proteins. Highly potent new macroscopic and microscopic methods have been developed to measure translational diffusion of membrane lipids and proteins. The microscopic methods can reveal diffusion via encounters between labeled molecules. Fluorescence anisotropy measurements are the most widely used techniques in biological research. The use of different permeant and non-permeant fluorophores have contributed much to a better understanding of the changes in the ordered states and motional freedom of the membrane phospholipids in different cells during development, aging and physiological functions as well as in pathological conditions. The application of fluorophores with non-random distribution have shed light on the asymmetrical changes between the outer and inner domain of the lipid bilayer and on the dynamics of 'flip-flop' in signal transduction. Membrane fluidity was shown to have a decisive role in the efficiency of ligand binding, in the outcome of direct cell to cell contacts and in the modulation of the activity of membrane enzymes. Cell filtrability reflects whole cell viscosity that can not always be correlated with the fine changes in membrane fluidity. Cell viscosity depends inter alia on the size and shape of the cells as well as on membrane rigidity. In contrast to this, membrane fluidity is only dependent on the freedom of mobility of the membrane constituents. Increased release of free radicals and reactive oxygen specie (ROS) affect membrane fluidity, cellular Ca2+ homeostasis, induce lipid peroxidation and finally cell death. Investigation of membrane fluidity proved to be a useful and sensitive additional method to obtain a better insight into the mechanisms by which different compounds, drugs and contact with foreign surfaces are affecting cellular functions. The measurements of membrane fluidity may gain more widespread use for monitoring the safety and efficacy of these actions. During the last few years, changes in membrane fluidity of blood cells have been reported during development and aging and as a result of physiological cell functions. Membrane fluidity changes have been described in thrombocythaemia, hyperlipidaemia, hypercholesterolaemia, hypertension, diabetes mellitus, obesity, septic conditions and in allergic and burnt patients, in alcoholics, in Alzheimer's disease and in schizophrenia. A short summary is given on red cell membrane fluidity changes in a Hungarian triosephosphate isomerase (TPI)-deficient family, reflecting how the very subtle changes in membrane fluidity can help to establish underlying biological differences between the clinical phenotypes of a severe enzyme (TPI) deficiency caused by the defect of a single gene in two brothers one with and one without neurological symptoms.
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PMID:Membrane fluidity of blood cells. 1465 48

The "lifestyle-related disease" has been increasing in Japan as the population advances in age and the food culture becomes westernized. Although prevention, treatment and therapy for this disease have been attempted using certain kinds of food and nutritive elements, so-called "health foods" such as DHA and EPA, which are mostly contained in fish oil, have been a special focus within these attempts. There have been many reports regarding the pharmacological functions and the mechanisms of DHA and EPA. Also, in the past few years, it has become possible to produce ingestible DHA and EPA oils, oils for chemical compounds, oils for animal feed, and highly purified DHA and EPA for medical and pharmaceutical use. EPA ethyl ester has a wide market as a preventive medicine in Japan. Initially in 1990, this medicine was administered in cases of arterisclerosis obliterans, using its anti-platelet aggregation ability. Four years later, in 1994, its effectiveness in triglyceride reduction was recognized, and its application was extended to cases of hyperlipidemia, which has remarkably broadened its market. Clinical studies with DHA have shown improvement in senile dementia (cerebral thrombosis, Alzheimer's disease), atopic dermatitis, and the ability to focus on moving objects, as well as control of aggressiveness against others caused by stress, and prevention of hyperlipidemia, hypertension, and cancer.
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PMID:[Importance of "health foods", EPA and DHA, for preventive medicine]. 1513 25


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