Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of a 26 year old woman who had been taking tranexamic acid to prevent uterine bleeding due to an IUD and who died from thrombosis of the left internal carotid artery is reported. The patient's father had died at age 54 of myocardial infarction. Otherwise the family history was entirely negative for thromboembolic disease. The patient was a mild smoker. She had been previously healthy and in particular, she was not affected with hypertension, diabetes, or dyslipidemia. She had carried to term 2 uncomplicated pregnancies. 40 days prior to hospital admission her gynecologist had inserted an IUD. The insertion of the IUD was followed by persistent uterine bleeding, and for this reason she began treatment with tranexamic acid (1.5 g/daily). Uterine bleeding persisted despite this treatment, and the IUD was removed. Because of persistence of a mild uterine bleeding, tranexamic acid was continued. 2 hours before admission the patient suddenly presented a left sided hemiparesis with disarthria and vomiting. On admission she was stuporous. The left side of her face drooped and the strength of the left arm and leg was markedly decreased. Both arm and leg reflexes were symmetrical. Her blood pressure was 110/70. An electroencephalogram on arrival confirmed a right sided cerebral lesion. Subsequently the patient's condition deteriorated rapidly. She developed a full left hemiplegia and became deeply comatose. A CAT scan performed 4 hours after admission showed no abnormalities. A CAT scan performed 3 days after admission showed a large cerebral infarction involving nearly the whole right cerebral hemisphere. The patient's condition remained essentially unchanged until she died 6 days after admission. Permission for autopsy was refused. Antifibrinolytic drugs competitively inhibit plasminogen activators and noncompetitively plasmin. Thromboembolic complications after the administration of antifibrinolytic drugs have long been recognized. The use of IUDs is often associated with troublesome uterine bleeding and particularly excessive menstrual bleeding. To avoid these complaints, antifibrinolytic drugs are increasingly used.
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PMID:Tranexamic acid, intrauterine contraceptive devices and fatal cerebral arterial thrombosis. Case report. 710 62

The fibrinolytic system is thought to be impaired in older hypertensive adults, thus contributing to the elevated risk of atherothrombosis, stroke, and acute myocardial infarction in this population. However, studies that have examined the fibrinolytic system in hypertensive individuals have failed to control for the confounding effects of other metabolic risk factors, making it difficult for one to determine the independent effect of hypertension on the fibrinolytic system. The purpose of the present study was to test the hypothesis that the fibrinolytic system is not impaired in older sedentary hypertensive men when the confounding effects of cardiovascular disease, diabetes, and dyslipidemia are controlled. Plasma concentrations of tissue-type plasminogen activator antigen and activity as well as plasminogen activator inhibitor-1 antigen and activity were measured under resting conditions in 12 hypertensive (69.4 +/- 1.4 years) and 11 normotensive 65.2 +/- 1.3 years) older men. The hypertensive and normotensive subjects had similar anthropometric and metabolic characteristics. There were no significant differences between the hypertensive and normotensive men in tissue-type plasminogen antigen (7.3 +/- 0.5 versus 6.1 +/- 0.6 ng/mL) and activity (1.8 +/- 0.3 versus 1.7 +/- 0.2 IU/mL) or plasminogen activator inhibitor-1 antigen (14.1 +/- 2.3 versus 10.8 +/- 2.2 ng/mL) and activity (17.4 +/- 1.2 versus 17.5 +/- 1.8 arbitrary units [AU]/mL) levels. In addition, the molar concentration ratio of active tissue type plasminogen activator to active plasminogen activator inhibitor-1 did not differ between the hypertensive (1:9.7 +/- 2.3) mmol/L) and normotensive (1:10.5 +/- 2.2 mmol/L) subjects, indicative of no impairment in fibrinolytic potential in either group. These results support the hypothesis that hypertension does not directly result in impaired fibrinolytic function in older adults. Furthermore, our findings suggest that abnormalities in fibrinolytic function in older hypertensive men are likely due to the primary effects of other metabolic disorders that usually accompany hypertension, such as hyperinsulinemia and dyslipidemia.
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PMID:The fibrinolytic system is not impaired in older men with hypertension. 862 Nov 96

Hypertension is often accompanied by a host of metabolic defects. Investigations have shown an association between insulin resistance, hyperinsulinemia, central/visceral obesity, and hypertension. Recent interest has focused on the fact that untreated hypertensive individuals have compensatory hyperinsulinemia, are resistant to insulin-mediated glucose uptake, and frequently have coexisting lipid abnormalities. Data from prospective studies appear to indicate that fasting hyperinsulinemia is an independent predictor of coronary artery disease. Additionally, there is evidence that hyperinsulinemia and diabetes eliminate the normal sex differences in the prevalence of coronary artery disease. The salutary effects of ovarian hormones on the prevalence of hypertension and cardiovascular disease in postmenopausal women are well established. Hyperandrogenism, in particular elevated serum levels of dehydroepiandrosterone sulfate, is believed to be a risk factor promoting sex-specific impairments of glucose and lipid metabolism, obesity, and hypertension in women. Clinical and epidemiologic evidence have linked elevated blood pressure to disturbances in lipoprotein metabolism, fibrinolytic activity, plasminogen activation inhibitor levels, and dyslipidemia. This review briefly presents the current understanding of various metabolic disturbances associated with hypertension, the pathophysiologic mechanisms involved, and the significance of the interplay between them relative to the complications of this disease.
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PMID:Metabolic abnormalities in hypertension. 926 63

Coronary artery disease is a leading cause of death in France. Some of its risk factors are well identified such as age, smoking, high blood pressure and dyslipidemia, but some others such as lipoprotein (a) (Lp(a)) are still under investigation. Lp(a) is an LDL-like particle to which is linked an apolipoprotein (a). The latter shows a high sequence homology with plasminogen that gives Lp(a) thrombogenic properties in addition to its atherogenic capacity. Many epidemiological studies have shown that a high plasma level of Lp(a) is a risk factor for coronary, cerebral and peripheral atherosclerosis. Out of thirteen prospective studies, ten have confirmed this result. The negative results from the three remaining studies were probably due to either the inadequate storage of the samples or the preventive drug treatment given to the patients during the studies and to the lack of standardization of Lp(a) assays. More over it has been shown that beside high plasma Lp(a) level, the presence of a low molecular weight Apo(a) isoform is also related to a higher incidence of coronary artery disease. This review of the literature clearly demonstrates the relationship between Lp(a) and atherosclerosis, and the need to measure Lp(a) in order to better evaluate the risk of atherosclerotic vascular disease especially in patients with a hyper LDLemia an early cardio- or cerebrovascular disease or a family history of atherosclerosis. Management of patients with high Lp(a) concentrations should be directed at minimizing all other risk factors for atherosclerotic disease.
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PMID:[Lipoprotein(a): risk factor for atherosclerotic vascular disease important to take into account in practice]. 1021 Jul 42

The polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease (CVD). Insulin resistance (IR), hyperandrogenism, and dyslipidemia are well-known cardiovascular risk factors in PCOS. Impaired fibrinolysis could also contribute to the development of CVD in PCOS. Global fibrinolytic capacity (GFC) is a recently developed method, which is reflected by the amount of generated D-dimer when the fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. We evaluated whether women with PCOS have any alterations in the GFC and other essential hemostatic parameters. Fifty-nine nonobese, normal glucose-tolerant women with PCOS (age, 22.9 +/- 4.4 yr; body mass index, 23.0 +/- 2.4 kg/m(2) ) and 23 age- and body mass index-matched healthy controls participated. We measured GFC and triglycerides; total cholesterol; HDL-cholesterol (HDL-C); lipoprotein-a; prothrombin time; partial thromboplastin time; thrombin time; antithrombin III; factors II, V, VII, and X; fibrinogen; plasminogen; antiplasmin; and D-dimer. Serum glucose and insulin (at baseline and during a 75-g 2-h oral glucose tolerance test) were also measured, and IR was assessed by homeostatic model assessment. GFC was significantly lower in the PCOS group, compared with the control group (2.49 +/- 1.6 vs. 5.95 +/- 2.43 microg/ml, P < 0.001). All the other coagulation and fibrinolysis parameters were comparable between the two groups. The PCOS group had lower HDL-C and higher IR values. GFC was correlated with testosterone and free testosterone negatively and with HDL-C positively. There was no correlation between GFC and any of the IR parameters. Our results suggest that women with PCOS have impaired fibrinolysis, as reflected by the decreased GFC. This impairment is not related to the IR and may increase the risk of CVD in PCOS.
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PMID:Global fibrinolytic capacity is decreased in polycystic ovary syndrome, suggesting a prothrombotic state. 1216 25

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

Thrombogenesis depends on the balance between coagulation and fibrinolysis in vasculature. Vascular endothelial cells (EC) synthesize activators and inhibitors for fibrinolysis, tissue and urokinase plasminogen activators (tPA and uPA) and plasminogen activator inhibitor-1 (PAI-1). Increased levels of PAI-1 with various levels of tPA have been frequently found in plasma of patients with coronary heart disease (CHD) or diabetes mellitus (DM). Dyslipidemia is common feature in patients with CHD or DM, which is characterized by elevated levels of total cholesterol, triglycerides, low or very low density lipoproteins (LDL or VLDL) and decreased levels of high density lipoprotein (HDL). LDL and VLDL stimulated the generation of PAI-1 from cultured EC. LDL and lipoprotein(a) [Lp(a)], another lipoprotein risk factor for CHD, reduced the generation of tPA from EC. HDL did not greatly alter the release of PAI-1 from EC. Oxidative modification by copper, ultraviolet or long exposure to EC enhanced the effect of LDL on the generation of PAI-1 and tPA from EC. Glycation amplified the effect of LDL and Lp(a) on the changes in the generation of the fibrinolytic regulators from EC. Treatment with antioxidants or HDL normalized glycated LDL-induced changes in the generation of fibrinolytic regulators from EC. Activation of protein kinase C is required for oxidized LDL or Lp(a)-induced PAI-1 production in EC. VLDL, but not LDL or its oxidized form, stimulated PAI-1 production through the activation of the VLDL-responsive element in the PAI-1 promoter. Plasma levels of fibrinolytic regulators in CHD or DM patients may be normalized by HMG-CoA reductase inhibitors and angiotensin II converting enzyme inhibitors. This review summarizes the up-to-date information on effects, mechanism and management for disorders in EC-derived fibrinolytic regulators induced by modified lipoproteins.
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PMID:Impact and mechanism for oxidized and glycated lipoproteins on generation of fibrinolytic regulators from vascular endothelial cells. 1284 45

Dyslipidemias are major risk factors for atherosclerosis and cardiovascular disease. Abnormalities of fibrinolytic and coagulation components are considered useful predictors of cardiovascular morbidity and mortality in adults. This study examined whether fibrinolytic and coagulation components are abnormal in children with dyslipidemia. Thirty-six children with asymptomatic dyslipidemia, and 26 control subjects underwent venous occlusion stress testing with collection of preocclusion and postocclusion blood samples. All samples were assayed for tissue plasminogen activator, plasminogen, plasminogen activator inhibitor-1, alpha(2)-antiplasmin, alpha(2)-macroglobulin, D-dimer, fibrinogen, and von Willebrand factor. Children with dyslipidemia had significantly decreased levels of tissue plasminogen activator in both preocclusion and postocclusion samples compared with control subjects, reflecting decreased fibrinolytic activity. Children with dyslipidemia also had significantly increased levels of plasminogen, alpha(2)-macroglobulin, and fibrinogen in preocclusion and postocclusion samples compared with control subjects. In conclusion, decreased fibrinolytic activity is present in asymptomatic children with dyslipidemias, potentially reflecting endothelial dysfunction and increased risk of cardiovascular disease in early adult life. Further studies are required to determine the usefulness of this marker in predicting disease progression or response to therapy.
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PMID:Impaired fibrinolytic activity is present in children with dyslipidemias. 1473 72

An increased amount of adipose tissue or its disproportionate distribution between central and peripheral body regions is related to the development of insulin resistance, type 2 diabetes mellitus, dyslipidemia, atherosclerosis, and coronary artery disease. Until recently, adipose tissue was regarded as a storage depot for lipids. It is now viewed as a hormonally active organ that plays a crucial metabolic role. The most important products of adipose tissue collectively referred to as adipocytokines, include adiponectin, leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), resistin, plasminogen-activating inhibitor-I (PAI-1), and angiotensinogen. These low and medium molecular weight proteins play an important role in the adipose tissue physiology and are believed to be a link between obesity, insulin resistance and endothelial dysfunction. This review describes the metabolic role of two of these proteins, adiponectin and leptin, in relation to insulin sensitivity.
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PMID:Adiponectin and leptin in relation to insulin sensitivity. 1837 Jun 42

Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are found in patients with type 2 diabetes mellitus which is associated with a dysbalance in glucose and lipid homeostasis. Especially a defective insulin response in the liver contributes to the development of hyperglycemia, dyslipidemia and peripheral insulin resistance and may contribute to hepatic over-expression of PAI-1 in diabetes type 2. Furthermore, a substantial upregulation of PAI-1 expression has also been shown in a variety of liver injury models. Thus, the liver appears to be not only a major site of PAI-1 synthesis in response to hormonal changes, but also in response to a variety of other pathological events. PAI-1 expression in liver largely depends on activation of signalling pathways and transcriptional regulators which may be the basis for a new level of cross-talk between different signalling pathways and thus may represent attractive therapeutic candidates. This article will primarily focus on the regulation of PAI-1 expression in liver cells and discuss potential cross-talks between metabolic, hormonal and environmental signals.
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PMID:Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: lessons from the liver. 1913 22


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