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)

Diabetes mellitus and hyperlipidemia are associated with coronary heart disease and with hypercoagulability, another independent risk factor for coronary heart disease. In 65 non-insulin-dependent diabetes mellitus patients [41 females, 24 males, median age 66 years (range 43-81 years)] treated with antidiabetic agents glycometabolic control (HbA1c), lipids (Quetelet index and blood lipids), and several coagulation parameters were studied in comparison with a reference group. Serum triglycerides were elevated [median (interquartile range) 2.3 (1.3) mmol/l vs. 1.6 (0.7) mmol/l in the controls (P < 0.001)], whereas the median lipoprotein(a) concentration was 65 (157) mg/l in the diabetic patients versus 44 (114) mg/l in the control group (not significantly different). Median high-density lipoprotein-cholesterol concentrations were slightly decreased in the diabetic patients: 1.2 (0.3) mmol/l compared with 1.3 (0.4) mmol/l in the control group (P < 0.02). Elevated levels of fibrinogen, fibrin monomers, thrombin-antithrombin III complex, and factor VIIIc were found in the diabetic patients and factor VII in male diabetic patients. These elevated coagulation parameters are indicators of an activated coagulation system in this patient group. By Spearman's rank test, only HbA1c values correlated with anti-thrombin III (r = 0.27, P < 0.03) and showed a tendency towards a correlation with lipoprotein(a) (r = 0.23, P < 0.07). Triglycerides correlated with the Quetelet index (r = 0.27, P < 0.03), high-density lipoprotein-cholesterol (r = -0.41, P < 0.001), and factor VII (r = 0.35, P < 0.01), whereas serum cholesterol concentrations correlated with factor VII (r = 0.27, P < 0.04) and with fibrin monomers (r = 0.29, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycometabolic control, lipids, and coagulation parameters in patients with non-insulin-dependent diabetes mellitus. 840 Mar 36

The cardiovascular risk factors blood pressure, overweight, hyperlipidaemia and several coagulation parameters were studied in a group of 54 otherwise healthy patients with essential hypertension of moderate severity. Of the 54 hypertensive patients, 43 were treated with anti-hypertensive drugs and 11 were not. The patients included in this study who were treated with anti-hypertensive drugs were still hypertensive in spite of their treatment. Lipoprotein levels and coagulation parameters did not differ between the untreated and treated hypertensive patients. Substantial percentages of patients were found to have hypertriglyceridaemia (46%), elevated LDL-cholesterol (28%) and elevated lipoprotein(a) concentrations (43%). Coagulation factors F VIIIc, fibrin monomer and factor VII in males were significantly elevated in comparison with a healthy reference group. These data are compatible with a moderate activation of the coagulation system. Correlations were established between systolic blood pressure and serum cholesterol (r = 0.43, p = 0.003), LDL-cholesterol (r = 0.34, p = 0.02) and triglycerides (r = 0.35, p = 0.01); Quetelet-index with fibrinogen (r = 0.37, p = 0.02) and thrombin-antithrombin III (r = 0.30, p = 0.04); and triglycerides with F VIIc (r = 0.34, p = 0.03) and fibrin monomer (r = 0.29, p = 0.04) respectively. These data link hypertension and hyperlipidaemia with increased coagulation activity and may contribute to our understanding of why these two cardiovascular risk factors accelerate atherogenesis.
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PMID:Coagulation factors and lipid composition of the blood in treated and untreated hypertensive patients. 846 17

Tissue factor pathway inhibitor (TFPI), a kunitztype inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic factors plasminogen activator inhibitor-1 (PA1-1) and tissue plasminogen activator (TPA) have been studied in various hyperlipidemias. Compared with a normal lipidic group, mean TFPI activity was 70% higher (P < .001) and 36% higher (P < .001) in type IIa and IIb hyperlipidemias, respectively, and was lower by 13% in type IV hyperlipidemia (P = .05). TFPI was correlated with LDL cholesterol (P < .001), total cholesterol (P < .001), HDL cholesterol (P < .01), apolipoproteins (apo) AI (P < .001) and B (P < .001) and lipoprotein a (P < .01). TFPI was negatively correlated with the triglyceride level (P < .05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which were decreased in type IV hyperlipidemia. FVIIc activity (P < .001) was increased by 30% in both type IV and type IIb hyperlipidemia and was correlated with triglyceride levels. FVIIa was not significantly increased in any group compared with control group. FVIIc was correlated with triglyceride level (P < .001), while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc (r = .5, P < .001) in the control group as well as in the hyperlipidemic groups (r = .32, P < .01). These results favor the hypothesis that higher FVIIc concentrations in hyperlipidemic patients are likely due to enhancement of synthesis of FVII and that a part of this FVII circulates in an activated chemical form. Compared with the control group, PAI-1 activity was twofold higher (P < .08) in type IIa hyperlipidemia, threefold higher (P < .001) in type IIb hyperlipidemia, and fourfold higher in type IV hyperlipidemia (P < .001). PAI-1 activity correlated with triglyceride levels (P < .001), apoB levels (P < .001) and total cholesterol levels (P < .05). These correlations were dependent on apoB and probably reflect the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI-1. Variation of TFPI activity appears to be related to the variations of its main lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic patients of hypercoagulability (increased FVIIc and decreased TFPI) and hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma induced by the injection of heparin.
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PMID:Levels of factor VIIc associated with decreased tissue factor pathway inhibitor and increased plasminogen activator inhibitor-1 in dyslipidemias. 854 30

Factor VII activity (FVIIc), a risk marker for coronary heart disease, is increased during postprandial lipemia. Factor VII activation accompanies lipolysis of triglyceride-rich lipoproteins, but the nature of this association and whether it is causal remain uncertain. To explore this issue, four patients with homozygous factor XII deficiency, four with complete factor XI deficiency, six with factor IX deficiency, and their respective age- and sex-matched controls were given two isocaloric dietary regimens, one providing on average 136 g fat and the other 19 g fat. Blood was taken before breakfast, immediately before lunch at 195 minutes, and at completion of the study at 390 minutes. All samples for each subject and matched control were assayed as one batch for FVIIc, activated factor VII, and factor VII antigen (FVIIag). Activation of factor VII was observed with the high-fat regimen but not with the low-fat regimen in all controls, factor XII-deficient patients, and factor XI-deficient patients. No factor VII activation was observed during either regimen in factor IX-deficient patients, but a normal postprandial responsiveness of factor VII to dietary fat was restored in one patient who replicated the study after factor IX therapy. Plasma FVIIag was not altered postprandially in either regimen in any group of patients or controls. Factor IX apparently plays an obligatory role in the postprandial activation of factor VII, although the mechanism remains to be determined.
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PMID:Activation of factor VII during alimentary lipemia occurs in healthy adults and patients with congenital factor XII or factor XI deficiency, but not in patients with factor IX deficiency. 863 77

Vascular access dysfunction is an important cause of morbidity for dialysis patients and a major contributor to hemodialysis cost. Thrombosis is a leading cause of vascular access failure, and usually results from stenotic lesions in the venous outflow system. This study was designed to explore the impact of serum levels of various risk factors for thrombosis and accelerated fibrointimal hyperplasia on progressive stenosis, and the subsequent thrombosis of hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was performed in 30 nondiabetic hemodialysis patients with primary arteriovenous fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography, and angiography were used to monitor vascular access patency. Eleven patients (37%) developed a progressive stenosis in the venous circuit, which was complicated by thrombosis in three patients. Compared with the patients without fistula dysfunction, these patients had higher serum levels of monocyte chemoattractant protein-1 and interleukin-6, two cytokines that regulate the proliferation of vascular smooth muscle cells, which is the key mechanism in the pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia, hyperlipidemia, and increased plasma levels of two hemostasis-derived risk factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII. Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL-cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and glucose/insulin were independent predictors of fistula dysfunction. This study demonstrates the influece of cytokines, hemostasis-derived vascular risk factor, hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary fistula survival. The assessment of these factors might be useful for the identification of the patients at risk of fistula stenosis and thrombosis.
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PMID:Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. 886 9

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.
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PMID:In vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway. 891 Dec 71

Modification of dietary fat composition may influence hemostatic variables, which are associated with increased risk of coronary heart disease (CHD). To address this question, we performed a controlled feeding study on 26 healthy male nonsmoking subjects with diets of differing fat composition. For the first 3 weeks, the subjects were given a diet calculated to supply 30% energy as total fat: 8% as monounsaturated, 4% as polyunsaturated, and 16% energy as saturated fatty acids, respectively (saturated diet). This was followed immediately by two diets taken in random order, each of 3-week duration and separated by an 8-week washout period on the subject's usual diet. Both diets were calculated to supply 30% of energy as fat: 14% monounsaturated, 6% as polyunsaturated, and 8% energy as saturated fatty acids. They both provided 5 g (approximately 1.7% energy) more of polyunsaturated fatty acids than the saturated fat diet; in one diet as long-chain n-3 fatty acids (n-3 diet) and in the other as linoleic acid (n-6 diet). Fasting plasma lipids, lipoproteins, and hemostatic factors were measured on the final 3 days of each dietary period. In a subset of 9 subjects the postprandial responses to a test meal were studied on the penultimate day of each period, each meal having the fat composition of its parent diet. On the n-3 diet compared with the n-6 diet, plasma triglyceride, HDL3 cholesterol, apoprotein AII, and fibrinogen concentrations were lower and HDL2 cholesterol concentration was higher (P = .0001, P = .003, P = .0001, P = .004, and P = .001, respectively). On both the n-3 and n-6 diets compared with the saturated diet, fasting plasma total and LDL cholesterol, apoprotein B, beta-thromboglobulin concentrations, and platelet counts were lower (P < .0001, P < .0001, P < .001, P < .01, and P < .05 respectively) and plasma Lp(a) and von Willebrand factor concentrations were higher (P = .02 and P < .01, respectively). Fasting factor VII coagulant activity (VIIc) was increased and apoprotein AI concentration reduced following the n-3 diet (P = .004 and P = .01, respectively) compared with the saturated diet. Plasma fibrinogen concentration was significantly greater following the n-6 diet than on the saturated diet (P = .02). Postprandially, plasma triglyceridemia was greater on the n-6 diet and lowest on the n-3 diet (P < .001) with the saturated diet being intermediate. Plasma VIIc was increased at 4 hours following the standardized test meals on the n-3 and n-6 diets (both P < .05) but not on the saturated diet. An increased intake of long chain n-3 fatty acids decreases fasting plasma triglyceride and apoprotein AII concentrations and increases HDL2 cholesterol concentrations and results in less postprandial lipemia but leads to an increase in VIIc. An increased intake of linoleic acid may raise plasma fibrinogen concentration. Decreasing the intake of saturated fatty acids reduces plasma LDL cholesterol and apoprotein B without affecting HDL cholesterol concentration independent of the type of polyunsaturated fatty acids in the diet. When advice is given to reduce saturated fat intake, it is important to ensure an appropriate ratio of n-3/n-6 fatty acids in the diet.
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PMID:Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. 943 92

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

Dietary therapy for ameliorating hyperlipidemia consists of several means. First of all, energy restriction is important, especially when the patient is obese. Secondary, restriction of total fat and saturated fatty acid intake is necessary. Energy from fat should be less than 25% of total energy and S:M:P ratio is recommended to be around 1:1-2:1-1.5. Cholesterol intake should be restricted below 300 mg and intake of dietary fiber and vegetable proteins should be increased. Hemostatic factors play an important role in the vessel diseases. A fat-rich diet increases activated factor VII. Many studies have reported inverse association between atherosclerotic disease and n-3 fatty acid consumption. We should maintain the present level of n-3 PUFA intake in Japan by keeping the n-6/n-3 ratio around 4.
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PMID:[Dietary therapy for thrombotic diseases of artery and vein]. 1042 64

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001<p<0.03). This decrease of monocyte TF expression in hyperlipidemic patients was not related to an increase of monocyte TFPI. Monocyte TF activity was negatively correlated to atherogenic fractions and positively correlated to protective fractions, specially after ex vivo LPS stimulation. Increased TFPI and FVII plasma levels were found in hyperlipidemic patients compared to controls. These results indicate an impairment of TF production by circulating monocytes from hyperlipidemic subjects, which is linked to the increase of atherogenic lipoprotein fractions. Further studies are required to elucidate the mechanism of this inhibition.
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PMID:Monocyte tissue factor response is decreased in patients with hyperlipidemia. 1059 31


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