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)

Hypercholesterolemia is seen as an important risk factor for coronary artery disease (CAD), as the incidence of CAD is strongly correlated with the level of serum cholesterol in epidemiological studies. However, hypercoagulability and reduced fibrinolytic capacity, often seen in survivors of myocardial infarction, are associated with hypertriglyceridemia (possibly concomitant with low levels of high-density lipoprotein cholesterol) and not with increased levels of total or low-density lipoprotein cholesterol. The important role of thrombogenesis in CAD is supported by the fact that initial high levels of plasma fibrinogen, coagulation factor VII (VIIc), and plasminogen activator inhibitor (PAI-1) are all independent risk factors for CAD or recurrent myocardial infarction as found in multivariate analyses of epidemiological studies. Furthermore, high plasma levels of VIIc and PAI-1 are associated with hypertriglyceridemia, reduced glucose tolerance, overweight, and hyperinsulinemia. The contribution of thrombogenic risk factors to the metabolic cardiovascular syndrome (MCVS) is thus established. Diet intervention is preferable for the normalization of hypercoagulability and hypofibrinolysis associated with MCVS. In familial combined hyperlipidemia, however, and especially with concomitant thromboembolic disease, diet alone is often not sufficient, and drug treatment with anticoagulants and/or lipid-lowering drugs may be necessary.
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PMID:Hypercoagulability and reduced fibrinolysis in hyperlipidemia: relationship to the metabolic cardiovascular syndrome. 128 67

In the 1970s in the Diet-Antismoking Trial, of the Oslo Study, colleagues and I found that the majority of high-risk men with elevated serum cholesterol and elevated triglyceride concentrations had impaired fibrinolytic capacity. Later on, both our group and others found a similar negative correlation between serum triglyceride levels and fibrinolytic capacity. Furthermore, in a prospective study of dietary intervention in individuals with both elevated cholesterol and triglyceride levels, we found that dietary lowering of serum triglyceride levels was significantly and positively correlated with an improvement in fibrinolytic capacity. In another study, we made the same observation for the coagulation factor VII-phospholipid complex: the more the triglycerides were reduced by diet, the greater was the change in factor VII complex. This correlation was highly significant and independent of changes in serum cholesterol. Platelet function is also influenced by dietary habits, but except for the effects of a fish oil-enriched diet, few data are available about the dietary effects on platelet function. It seems, however, that in individuals with elevated lipid levels and elevated blood pressure, increased platelet reactivity is a highly prevalent finding. Many of the hemostatic risk variables are associated with the so-called "metabolic risk syndrome" characterized by an increase in serum insulin level, together with increased relative body weight, mild hypertension, hyperlipidemia, and physical inactivity. This syndrome can often be influenced favorably by life-style changes. A controlled study with interventions in diet and activity level has just been started by our group.
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PMID:The influence of dietary change on hemostatic risk variables. 134 3

There is evidence that the increase in coagulation factor VII (FVII) represents a predictive risk factor of arterial thrombosis in coronary heart disease. Its relative contribution to this multifactorial process and its relationship to other risk factors, namely cholesterol and triglycerides, is yet a matter of investigation. In this study we aimed to clarify whether FVII synthesis or activation correlated with plasma lipid concentrations. For this, we assayed the plasma levels of FVII antigen (FVII:ag) and FVII coagulant activity (FVIIc) in types IIa, IIb and IV hyperlipidemic individuals, together with the levels of cholesterol, triglycerides, high-density lipoproteins and apolipoprotein B. FVII activation state (FVIIa) was then assessed by FVIIc/FVII:ag. In order to assess the possible correlation of FVII levels with the generation of thrombin and formation of fibrin, we also assayed the plasma concentration of fibrin degradation products (D-dimers) in these patients. Considering all the patients studied, there was a fair correlation between FVIIc and FVII:ag (r = 0.704; p less than 0.01). The mean levels of FVIIc and FVII:ag were significantly higher in type IV hyperlipidemia than in controls (t = 4.260; p less than 0.001 and t = 3.015; p less than 0.01, respectively) and other types of hyperlipidemia. We also found that FVIIc and FVII:ag significantly correlated to triglyceride concentration. We could not detect an evident activation of FVII in these patients since FVIIc/FVII:ag was not elevated in comparison with controls, nor did it correlate with any of the lipid determinations in any of the types of hyperlipidemia studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma factor VII, triglyceride concentration and fibrin degradation products in primary hyperlipidemia: a clinical and laboratory study. 273 79

Dietary studies have established a connection between plasma lipoproteins and coagulation factor VII. The present study was undertaken to specifically examine whether factor VII is activated during alimentary lipemia and to investigate the relations of factor VII mass and activity state with fasting and postprandial lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore determined in plasma samples taken before and after intake of a standardized, oral fat load of a mixed-meal type in 33 men (mean age +/- SD, 48.8 +/- 3.2 years) with a previous myocardial infarction at a young age and 10 healthy, age-matched control subjects. A panel of methods for factor VII determination was used to ensure that changes in all potentially existing forms of the factor during alimentary lipemia would be included. Substantial activation of factor VII was found to occur during alimentary lipemia, whereas the number of factor VII molecules remained constant or even appeared to decrease after the test meal. Activation of factor VII was more pronounced in control subjects than patients, and the proportion of activated factor VII molecules was higher in control subjects. Interestingly, factor VII activation, which correlated quantitatively with the degree of postprandial triglyceridemia, seemed to be related to FFA production during lipolysis of triglyceride-rich lipoproteins that were generated in response to fat intake. Postheparin plasma lipoprotein lipase activity was lower in patients, which could offer one explanation why factor VII activity was lower during alimentary lipemia in these subjects despite their exaggerated postprandial triglyceridemia. Thus, activation of coagulation factor VII during alimentary lipemia may result in a procoagulant state that is likely to promote the formation of a coronary thrombus in individuals with established coronary artery disease.
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PMID:Activation of coagulation factor VII during alimentary lipemia. 827 79

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

Favourable effects of n-3 fatty acids on the atherogenic risk profile were recently demonstrated in subjects with combined (type IIb) hyperlipidaemia, not responding to a therapeutic diet. Re-examination of a previous patient material was performed to assess the influence of n-3 fatty acids on homocysteine and several coagulation factors. Subjects were randomly allocated to receive either a concentrated compound of 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (n = 28), or corn oil (n = 29), in a daily dose of 4g for 12 weeks. The intervention was double-blind. Homocysteine remained unchanged in both groups after 12-week treatment. N-3 fatty acids supplementation did not affect the levels of fibrinogen, coagulation factor VII or tissue factor pathway inhibitor (TFPI), while plasminogen activator inhibitor (PAI) increased significantly (Student's t-test; p <0.05). Total blood platelets were significantly reduced in subjects receiving n-3 fatty acids (Student's t-test; p <0.05), whereas bleeding times increased non-significantly.
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PMID:Atherothrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia. 1023 39

Elevated plasma triacylglycerol (TG; triglyceride) concentrations, especially in the postprandial state, have been associated with an increased risk of coronary heart disease (CHD). Postprandial lipemia represents a complex series of reactions which occur following the ingestion of a meal containing fat and is associated with a number of adverse metabolic events including the production of atherogenic chylomicron remnants, the formation of the highly atherogenic small dense low density lipoprotein particles, a reduction in the concentration of the cardioprotective high density lipoprotein fraction and the activation of coagulation factor VII. Fish oils are a rich source of the long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid and docosahexaenoic acid. Long chain n-3 PUFA are effective hypotriglyceridemic agents, lowering both fasting and postprandial TG concentrations. There is a large body of evidence which shows that n-3 PUFA reduces plasma TG concentrations through reduced endogenous very low density lipoprotein production. This in turn may account for the reduced postprandial lipemic response following n-3 PUFA supplementation. However, this does not preclude a contribution of enhanced chylomicron clearance, which may be mediated through altered chylomicron size, structure or chemical composition, or altered lipoprotein lipase metabolism in terms of enzyme concentration, activity, or affinity for chylomicrons. However the precise biochemical nature of this effect remains to be established. The reduction of postprandial plasma TG concentrations by n-3 PUFA may partly explain why n-3 PUFA intake is inversely related to CHD mortality.
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PMID:Long-chain n-3 polyunsaturated fatty acids and triacylglycerol metabolism in the postprandial state. 1041 73

Several clinical studies have shown that the magnitude and duration of postprandial lipemia is positively related to the pathogenesis and progression of coronary heart disease. Postprandial lipid metabolism refers to the series of metabolic events that occur following the ingestion of a meal containing fat. Dietary fat is principally composed of triacylglycerol, postprandial lipaemia therefore being characterized by an increase in plasma triacylglycerol concentration. This review will describe the nature of the postprandial response and show the direct and indirect pro-atherogenic effects of triacylglycerol-rich lipoprotein metabolism. An elevated postprandial lipemic response precipitates a number of adverse metabolic events, including the production of atherogenic chylomicron remnants, the formation of the highly atherogenic small, dense low-density lipoprotein particles, and a reduction in the concentration of the cardioprotective high-density lipoprotein fraction. Postprandial lipemia also interacts with the process of thrombosis, in that an elevated postprandial triacylglycerol-rich lipoprotein concentration has the ability to activate the coagulation factor VII and plasminogen activator inhibitor. In the light of the potential impact of an elevated postprandial lipemia on atherothrombosis, the genetic determinants of the magnitude of the postprandial response will be identified. Finally, the nutritional factors that modulate the postprandial response will also be discussed.
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PMID:The impact of postprandial lipemia in accelerating atherothrombosis. 1114 61