UMLS:C0020473 - FACTA Search

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)

Mortality rates associated with cardiovascular disease (CVD) are high in long-term dialysis patients. Increased levels of plasma fibrinogen (FBG), coagulation factor VII (FVII), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) as well as hyperlipidemia are regarded as important risk factors for CVD. To investigate whether there are differences in the risk of CVD between chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients, serum lipid levels and plasma FBG, FVII, t-PA, and PAI-1 levels were measured in 17 patients on HD and 17 patients on CAPD. FBG was measured by the thrombin time method, FVII activity (FVIIc) by the chromogenic prothrombin time method, and t-PA and PAI-1 activity by the chromogenic substrate assay. No difference was found in body mass index (BMI) between HD and CAPD patients. Total cholesterol (TC), TC/high-density lipoprotein (HDL)-C ratio, low-density lipoprotein (LDL)-C, and triglycerides (TG) were significantly increased, and HDL-C was significantly decreased in CAPD patients compared with HD patients. FBG and FVIIc were significantly elevated in CAPD patients compared with controls or HD patients. T-PA activities were significantly higher in HD and CAPD patients than in controls. CAPD patients showed significantly higher PAI-1 activities than controls or HD patients. Significant positive correlations were found between FBG or FVIIc and TC, between FBG and LDL-C or TG, and between FVIIc and LDL-C in these patients. T-PA showed significant negative correlations with FBG, PAI-1, TC, LDL-C, and TG. There was a significant positive correlation between PAI-1 and TG and a significant negative correlation between PAI-1 and HDL-C. We conclude that CAPD patients may have a greater risk of CVD than do HD patients, and that coagulation and fibrinolytic activity are correlated with lipid disorders in these patients.
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PMID:Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. 865 Dec 50

Obesity is commonly associated with insulin resistance. The etiology of insulin resistance syndrome such as syndrome X or deadly quartet is not clear. We have proposed visceral fat syndrome, in which fat accumulation is predominant in the intra-abdominal cavity, frequently accompanied by disorders of glucose and lipid metabolism, and also hypertension. Excess free fatty acid of the portal circulation may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis. Enhanced production of PAI-1 by increased visceral fat may be partly responsible for the development of cardiovascular disease in patient with visceral fat assmulation.
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PMID:[Obesity and insulin resistance syndrome]. 891 27

We studied the involvement of coagulation and fibrinolysis system in the induction and development of atherosclerosis in rabbits with hyperlipidemia induced by a high-cholesterol diet (HCD). In HCD rabbits, plasma lipids and atherogenic indices were maintained at a high level throughout the experimental period compared with those in rabbits fed on a standard diet. In the early phase, a significant increase in fibrinogen level was followed by increases in the activities of plasminogen and tissue-type plasminogen activator with a decrease in alpha 2-plasmin inhibitor activity and platelet count. In the middle and late phases, significant increases in plasminogen activator inhibitor-1 and antithrombin-III were observed in HCD rabbits. These results suggest that the early enhancement of coagulation followed by high activity of fibrinolysis is involved in the induction and development of hyperlipidemic thromboembolism and atherosclerosis in HCD rabbits.
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PMID:Involvement of enhanced coagulation and fibrinolysis system in induction of atherosclerosis in hyperlipidemic rabbits fed on a high cholesterol diet. 917 3

Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involved in the mechanism of atherosclerosis in this syndrome. Previously we revealed that the plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that the PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The results show a high concentration of plasma PAI-1. One of the well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentrations of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentrations of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome.
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PMID:Increased blood plasminogen activator inhibitor-1 and intercellular adhesion molecule-1 as possible risk factors of atherosclerosis in Werner syndrome. 918 38

We investigated the usefulness of the fluorogenic prothrombin time (FPT) for detection of hypercoagulability and its association with hyperlipidemia in 19 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy control subjects, compared with plasma levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and D-dimer. We also evaluated the effect of bezafibrate on hypercoagulability in 10 hyperlipidemic NIDDM patients. The plasma levels of FPT and fibrinogen were significantly higher in hyperlipidemic NIDDM patients than in normolipidemic NIDDM patients and controls. Plasma levels of PAI-1 and D-dimer were significantly higher in normolipidemic and hyperlipidemic NIDDM patients compared with controls. The FPT was correlated with the HbA1c, the body mass index, and levels of total cholesterol, fibrinogen and PAI-1. Six-months therapy with bezafibrate reduced the levels of FPT, triglycerides and basal insulin, but did not alter levels of fibrinogen, PAI-1 and D-dimer. Our results showed that the FPT was useful for detection of hypercoagulability and evaluation of the effect of drugs. The increased FPT in patients with NIDDM suggested that hypercoagulability was present in association with hyperlipidemia.
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PMID:Effect of bezafibrate on hypercoagulability assessed by fluorogenic prothrombin time in hyperlipidemic patients with non-insulin-dependent diabetes mellitus. 921 24

The fibrinolytic and metabolic changes associated with gemfibrozil treatment of hypertriglyceridemia were evaluated in 16 patients with type IV hyperlipidemia by criteria of triglyceride levels > 250 mg/dl and total cholesterol levels < 220 mg/dl. The plasma triglyceride level was significantly lower (323 +/- 71 vs 189 +/- 57 mg/dl; p = 0.000) and high-density lipoprotein cholesterol level significantly higher (33.5 +/- 4.6 vs 38.0 +/- 6.7 mg/dl; p = 0.005) after 3 to 4 months of gemfibrozil treatment. However, the glucose and insulin metabolism measured by oral glucose challenge and insulin suppression tests showed no significant changes after gemfibrozil therapy. In contrast, plasma plasminogen activator inhibitor-1 antigen (36.9 +/- 12.4 vs 27.3 +/- 11.4 ng/ml; p = 0.008) and activity (15.5 +/- 5.5 vs 11.8 +/- 3.0 IU/ml; p = 0.009) and tissue plasminogen activator antigen (13.2 +/- 4.0 vs 10.4 +/- 3.7 ng/ml; p = 0.007) were significantly depressed, and tissue plasimogen activator activity (0.57 +/- 0.31 vs 0.69 +/- 0.38 IU/ml; p = 0.015) was significantly elevated by gemfibrozil. The data indicate that lowering plasma triglyceride and raising high-density lipoprotein cholesterol levels by gemfibrozil treatment also improved the fibrinolytic system without changes of insulin resistance and glucose intolerance in patients with isolated hypertriglyceridemia.
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PMID:Gemfibrozil treatment of hypertriglyceridemia: improvement on fibrinolysis without change of insulin resistance. 932 17

Accelerated coronary artery disease is the most serious obstacle to long-term survival in heart transplant recipients. Hyperlipemia, hyperinsulinism, and changes in endothelial cell hemostatic function have been implicated in cardiac allograft vascular disease. Both lovastatin and bezafibrate are safe, effective, and well tolerated therapies for hyperlipidemia. Our study compares the effect of these lipid-lowering drugs in 21 patients with post-heart transplantation hyperlipidemia on different risk factors related to insulin resistance syndrome. Patients were given the same diet for 3 months, then randomized to lovastatin or bezafibrate for a period of 8 weeks, and crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. Transplant patients had higher insulin (35 +/- 3 vs 24 +/- 3 microIU/L), fibrinogen (298 +/- 15 vs 261 +/- 14 mg/dl), and plasminogen activator inhibitor-1 (PAI-1) (17 +/- 2 vs 11.7 +/- 2 arbitrary units/ml) plasma levels than controls. Significant decreases in insulin (-37 +/- 3%), fibrinogen (-12 +/- 4%), and PAI-1 plasma levels (-18 +/- 12%) were only observed after bezafibrate treatment. In conclusion, bezafibrate decreases plasma insulin, fibrinogen, and PAI-1 in hyperlipidemic heart transplant recipients.
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PMID:Comparison of bezafibrate versus lovastatin for lowering plasma insulin, fibrinogen, and plasminogen activator inhibitor-1 concentrations in hyperlipemic heart transplant patients. 938 94

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
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PMID:Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C. 943 45

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
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PMID:Management of dyslipidemia in adults with diabetes. 953 88

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