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)

Platelet aggregability and plasma factor VIII-related antigen (F. VIIIR:AG) level in 16 ischemic heart disease (IHD) patients were increased by isometric exercise and these changes were prevented by administration of a lipid lowering agent, simfibrate, a derivative of clofibrate. Serum total cholesterol (TC) level decreased and the high density lipoprotein-cholesterol (HDL-C)/TC ratio increased with the treatment. Another 7 hyperlipidemics were administered with simfibrate. Platelet malondialdehyde (MDA) production decreased with improvement in lipid profile. In an in vitro study, platelet aggregability and the plasma level of von Willebrand factor (vWF) and F.VIIIR:AG of normal citrated blood were increased by passing it through a glass bead column. Combining above results of the three separate studies, it would be suggested that hyperlipidemia might enhance platelet activation in vivo, which occurred through contact of platelets to atherosclerotic rough vessel surface. The anti-platelet effect of simfibrate might be mediated through its effect on arachidonic pathway in platelets.
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PMID:Influence of lipids metabolism on platelet activation in vivo. 641 24

The purpose of this investigation was to evaluate the benefits and the potential risks of a very low calorie protein-diet in obese patients with metabolic abnormalities and at increased cardiovascular risk. To this end, the 420 kcal diet (with 50% of energy as protein) was administered for 10 days to 10 grossly obese subjects with glucose intolerance, hyperlipemia, arterial hypertension, ischemic cardiopathy and thrombotic risk related to high levels of fibrinogen factor VIII and reduced fibrinolytic activity. Weights loss averaged 360 g/day with a mean protein loss of 17 g/day occurring essentially during the very early phase of the diet. There was a rapid normalisation of blood pressure, plasma lipids and glycaemia. With the exception of a slightly negative potassium balance other ion remained in balance. There was no change in electrocardiogram, in parameters of blood coagulation or in hepatic and renal function. There was only a moderate increase in ketonaemia and plasma urate. It appears therefore, that an 8 to 10 day very low calorie protein-diet is well tolerated even in obese patients with increased cardiovascular risk, and that it corrects of several metabolic abnormalities without alteration in cardiac, hepatic or renal function.
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PMID:[Evaluation of tolerance of a modified protein diet in obese subjects]. 665 61

Accumulation of plasminogen activator inhibitor type 1 (PAI-1) in the arterial wall may accelerate atherogenesis by inhibiting fibrinolysis, diminishing proteolysis of extracellular matrix proteins, or modifying migration of vascular smooth muscle cells. Increased intramural expression of the PAI-1 gene is induced by thrombosis. To determine whether it occurs also in response to a sustained mechanical insult to endothelium, hypercholesterolemia, or both, rabbits were subjected to sustained aortic injury induced by implantation of indwelling polyethylene tubing, to hyperlipidemia induced by cholesterol and peanut oil feeding over a period of 8 weeks, or both. Sustained vascular injury alone did not increase plasma PAI-1. However, hypercholesterolemia with or without mechanically induced vascular injury increased plasma PAI-1 twofold. The expression of PAI-1 mRNA in aorta (Northern blots) was significantly increased when vascular injury was combined with hyperlipidemia. In situ hybridization showed that the increase with mechanical injury alone occurred in endothelial cells covering the neointima (positive for factor VIII and thrombomodulin), in abnormally differentiated vascular smooth muscle cells (positive for embryonic myosin heavy chain), and in macrophages (positive for the RAM-11 anti-macrophage antibody). Qualitatively similar but much more marked increases in PAI-1 gene expression were seen when arterial injury was accompanied by hypercholesterolemia. Neither vitronectin, known to stabilize PAI-1, nor vitronectin mRNA increased in liver. However, immunocytochemistry and Western blots demonstrated marked aortic accumulation of vitronectin protein with hyperlipidemia, particularly in subendothelial fibrotic regions, accompanied by increased neointimal vitronectin mRNA as shown by in situ hybridization. These results suggest that increased synthesis and stabilization of vascular PAI-1 may potentiate accumulation of extracellular matrix, thereby accelerating atherosclerosis.
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PMID:Potentiation by hypercholesterolemia of the induction of aortic intramural synthesis of plasminogen activator inhibitor type 1 by endothelial injury. 769 Mar 10

The platelet function as well as parameters of lipid metabolism and glucose tolerance were investigated in 30 men with occlusive atherosclerotic arterial disease of the low extremities (IIIB or IV Fontaine's stage). The platelet aggregation, platelet survival, activity of intraplatelet metabolism of arachidonic acid, radiofibrinogen binding to platelet, circulating platelet aggregates and both the activity of factor VIII and the concentration of von Willebrand factor antigen in the plasma were measured. In the majority of patients the impairment of platelet aggregation with ADP, enhancement of radiofibrinogen binding to platelets and an increase of factor VIII level in the plasma were established. There was an interrelationship between platelet dysfunction and disturbances of lipid metabolism. Platelet survival was shortened in patients with moderate hyperlipidemia and correlated with a concentration of HDL-cholesterol in the serum. The radiofibrinogen binding to platelets was the most pronounced in patients with severe hyperlipidemia and correlated with a concentration of total cholesterol in the serum. The results may suggest the potential usefulness of antiplatelet drugs in patients with occlusive atherosclerotic arterial disease.
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PMID:[Function of platelets in patients with occlusive atherosclerotic arterial disease of the lower extremities]. 808 11

The role of hemostatic variables (which promote hemostatic plugs and thrombi) and rheological variables (which affect blood flow) in the pathogenesis of vascular diseases (ischemic heart disease, stroke, and peripheral arterial disease) is reviewed, with emphasis on epidemiological studies. Rheological variables are consistently associated with both prevalent and incident cardiovascular disease. These associations are only partly explained by conventional risk factors. The predictive value of plasma viscosity for cardiovascular events is partly explained by fibrinogen, and partly by lipoproteins. The associations of whole blood viscosity with cardiovascular disease are partly explained by plasma viscosity and partly by hematocrit. White cell count, but not platelet count, predicts ischemic heart disease events. Cigarette smokers have higher levels of rheological variables than non-smokers, these increases are partly or wholly reversible in ex-smokers. Lipoprotein reduction by pravastatin lowers plasma and whole-blood viscosity, which may be one mechanism through which lipid lowering produces an early reduction in cardiovascular events. Data from the Edinburgh Artery Study suggest that viscosity is related both to the extent of atherosclerosis, and to ischemia in the presence of a given degree of atherosclerotic stenoses. Among hemostatic variables, fibrinogen, factor VIII: vWF complex, tpA antigen, and fibrin D-dimer are associated with both prevalent and incident cardiovascular disease. Again, these associations are only partly explained by conventional risk factors They suggest that endothelial disturbance and increased fibrin turnover may play roles in cardiovascular disease. Hemostatic and rheological variables are therefore associated with both prevalent and incident cardiovascular disease, and may be mechanisms through which risk factors such as smoking, hyperlipidemia and infections (including oral infections) promote vascular events.
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PMID:Etiopathogenesis of cardiovascular disease: hemostasis, thrombosis, and vascular medicine. 972 96

Monoclonal antibody therapies have conducted to not only hematologic malignancies but also disorders of hemostasis and coagulation. This article describes the recent advances of monoclonal antibody therapy for bleeding disorders such as idiopathic thrombocytopenic purpura(ITP), hemophilia A, disseminated intravascular coagulation(DIC), and thrombosis. Rituximab, chimeric anti-CD20 monoclonal antibody treatment has a valuable effect in the patients with ITP, and clinical trials using anti-CD40 ligand monoclonal antibody for ITP are underway. Anti-CD40 ligand monoclonal antibody can be an alternative therapy for hemophilia A patients with inhibitors to factor VIII. In thrombosis, anti-tissue factor monoclonal antibody and anti-factor IX(a) monoclonal antibody were established as novel anticoagulant regents. Plasminogen activator inhibitor-1(PAI-1) increases in endotoxin-induced DIC and many thrombotic diseases such as myocardial infarction, type 2 diabetes mellitus, and hyperlipidemia. Anti-PAI-1 monoclonal antibody reduced fibrin deposition in DIC mouse model. Treatment of these monoclonal antibodies for the molecules regulating coagulation-fibrinolysis system may be utilized for acute coronary syndrome and venous thrombosis.
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PMID:[Monoclonal antibody therapy for disorders of hemostasis and coagulation]. 1190 68

Platelet activation, impairment of fibrinolysis, activation of the coagulation pathway, and dyslipidemia are important factors in the pathogenesis and progression of ischemic heart disease, and patients generally need to use an antiplatelet agent. Lipid-lowering cerivastatin, a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was administered to 20 patients with primary mixed hyperlipidemia for the assessment of the effect of cerivastatin on lipid levels, plasma fibrinogen concentration, factor VII, VIII, and X levels, plasminogen and antiplasmin concentrations, platelet count, and aggregation (adenosine diphosphate [ADP], collagen, and epinephrine induced). Assessments were made immediately after 2 months of a standard lipid-lowering diet, 4 weeks of placebo administration, and 4 weeks of cerivastatin treatment. Cerivastatin achieved significant reductions in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The significant improvement of the lipid profile was associated with platelet aggregation reduction in vitro stimulated by ADP, collagen, and epinephrine (P < .05, P = .05, P < .005, respectively). Significantly lower levels of factor VII and fibrinogen were observed (P = .001, P < .0001) immediately after cerivastatin treatment. No significant differences were detected in factor VIII level, plasminogen and antiplasmin concentrations, and platelet count after cerivastatin treatment. It was concluded that cerivastatin in mixed hyperlipidemia can exert beneficial changes on specific hemostatic variables and platelet aggregation in addition to its positive effects on plasma lipid values.
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PMID:Treatment with cerivastatin in primary mixed hyperlipidemia induces changes in platelet aggregation and coagulation system components. 1241 40

Acquired hemophilia A (AHA) is a rare coagulation disorder due to the development of an autoantibody against and inhibitor of coagulation factor VIII. It has been reported that immunosuppressive therapy with corticosteroids, cyclophosphamide, azathioprine and vincristine are effective to decrease this inhibitor. When corticosteroids and cytotoxic drugs are ineffective, cyclosporine A (CyA) may be effective as a second-line salvage therapy. Except for postpartum conditions, AHA usually occurs in elderly patients who are often already suffering from diabetes mellitus, ischemic heart disease and/or hyperlipidemia. However, immunosuppressive and cytotoxic drugs may have adverse effects on these patients. We report on a 66-year-old man who developed AHA after colon cancer resection (factor VIII inhibitor: 61 Bethesda units/ml, aPTT : 97.9 s). Since he already had both diabetes mellitus and ischemic heart disease, we abandoned treatment with corticosteroids and oral cyclophosphamide was started, but was switched to CyA because of leukopenia. Within 3 months of starting the CyA treatment, aPTT levels returned to normal and 4 further months were required for complete eradication of the inhibitor. This case revealed that CyA is as effective as corticosteroids for AHA. For patients with AHA who have unfavorable complications due to corticosteroids and cytotoxic drugs, CyA could be a potential first-line drug.
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PMID:[Cyclosporine A as an effective treatment for a patient with acquired hemophilia A complicated with diabetes mellitus and ischemic heart disease]. 1644 Jul 70

A 66-year-old man with hypertension and hyperlipidemia developed a hemorrhagic stomal ulcer and massive hematoma of the face at 4 and 7 months, respectively, after fundusectomy for early gastric cancer. The diagnosis of acquired hemophilia A was made based on the marked prolongation of activated partial thromboplastin time, an extremely low factor VIII activity, and a very high-titer factor VIII inhibitor. After admission, oral prednisolone and cyclophosphamide were started. In addition, activated prothrombin complex concentrates and recombinant activated factor VII were intravenously administered which successfully controlled his hemorrhage. Only 1 week after the episode of bleeding, however, he complained of abdominal pain accompanied by watery stool with fresh blood. The diagnosis of ischemic colitis was made based on the clinical course and the findings on both CT-scan and colon fiberoscopy. The colitis spontaneously and quickly resolved with conservative observation. To the best of our knowledge, this is the first reported case of ischemic colitis that occurred in an acquired hemophilia patient without simultaneous administration of coagulation factors or antifibrinolytic agents. We should thus pay attention to the possible occurrence of thrombotic events even in acquired hemophilia patients in the presence of risk factors for thrombosis.
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PMID:[Ischemic colitis following the treatment of acute hemorrhage in a patient with acquired hemophilia A]. 1671 66

Elevated levels of factor VIII:c (elevated FVIII:c) are associated with an increased risk for venous thromboembolism (VTE) and arterial vascular events, and are at least in part determined genetically. We prospectively followed 192 asymptomatic individuals with elevated FVIII:c (>150%) and 340 with normal levels for an average duration of 31 months (range 7 to 56 months) to investigate the risk of VTE and arterial vascular events. Participants were first degree relatives of consecutive patients with elevated FVIII:c and VTE or arterial vascular events before the age of 50 years. The incidences of VTE were 1.25% (0.46-2.73) per year in the subjects with elevated FVIII:c, versus 0.23% (0.03-0.82) in those with normal levels (OR 5.5 [1.1-27.3]). The annual incidences of arterial vascular events were 1.04% (0.34-2.42) and 0.23% (0.03-0.82) in relatives with and without elevated levels of FVIII:c, respectively (OR: 4.5 [0.9-23.5]). After adjustment for age, smoking, known diabetes mellitus, hyperlipidemia, and hypertension, the odds ratio for any event was 3.7 (1.1-13.1). In conclusion, asymptomatic individuals with elevated FVIII:c levels and a positive family history of VTE or arterial vascular events before the age of 50 appear to have a high annual incidence of first VTE and arterial vascular events. Elevated FVIII:c may be a common risk factor for both clinical entities.
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PMID:Absolute annual incidences of first events of venous thromboembolism and arterial vascular events in individuals with elevated FVIII:c. A prospective family cohort study. 1800 Jun 9


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