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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors.
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PMID:Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study. 834 95

Increased urinary albumin loss in patients with Type 1 diabetes is associated with accelerated atherosclerosis. Prothrombotic factors known to be associated with cerebrovascular and coronary artery disease in the general population, antithrombotic factors, were studied in 52 patients with Type 1 diabetes and varying urinary albumin loss and 24 non-diabetic control subjects. Fibrinogen increased from 2.5 g l-1 (95% confidence interval 2.3-2.8) in control subjects and 2.8 g l-1 (2.6-3.0) in diabetic patients without microalbuminuria to 3.1 g l-1 (2.7-3.5) with microalbuminuria (p < 0.005 vs control; p < 0.001 vs without microalbuminuria). Factor VIIc increased from 81% (75-86% in non-diabetic control subjects and 84% (78-90%) in diabetic patients without microalbuminuria to 103% (89-117%) with microalbuminuria (p < 0.005 vs control; p < 0.05 vs without microalbuminuria) and 118% (86-150%) with albuminuria (p < 0.005 vs control and p < 0.001 vs without microalbuminuria). Levels of the antithrombotic factors protein C, protein S, and antithrombin III also rose in the diabetic patients with evidence of renal damage. Elevation of prothrombotic factors has been associated with increased risk of microvascular disease, whereas elevation of antithrombotic factors has no known protective effect. Therefore, this pattern of alteration of haemostatic factors in diabetic renal disease may contribute to the increased risk of vascular disease associated with both microalbuminuria and albuminuria.
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PMID:Prothrombotic and antithrombotic factors are elevated in patients with type 1 diabetes complicated by microalbuminuria. 845 88

Growing evidence suggests that moderately elevated levels of homocysteine are associated not only with arterial thrombosis and atherosclerosis but also with venous thrombosis as well. We have reviewed recent studies that indicate that homocysteine inhibits several different anticoagulant mechanisms that are mediated by the vascular endothelium. The protein C enzyme system appears to be one of the most important anticoagulant pathways in the blood. Homocysteine inhibits the expression and activity of endothelial cell surface thrombomodulin, the thrombin cofactor responsible for protein C activation. Homocysteine inhibits the antithrombin III binding activity of endothelial heparan sulfate proteoglycan, thereby suppressing the anticoagulant effect of antithrombin III. Homocysteine also inhibits the ecto-ADPase activity of human umbilical vein endothelial cells (HUVECS). Because ADP is a potent platelet aggregatory agent, this action of homocysteine is prothrombotic. Homocysteine also interferes with the fibrinolytic properties of the endothelial surface because it inhibits the binding of tissue plasminogen activator. Homocysteine stimulates HUVEC tissue factor activity. We have found that lipoprotein(a) [Lp(a)] also stimulates HUVEC tissue factor activity. The combination of Lp(a) plus homocysteine induced more tissue factor activity than either agent alone. These disruptions in several different vessel wall-related anticoagulant functions provide plausable mechanisms for the occurrence of thrombosis in hyperhomocysteinemia.
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PMID:Homocysteine and hemostasis: pathogenic mechanisms predisposing to thrombosis. 864 72

Thrombosis occurs when there is a breakdown in the balance between thrombogenic factors and protective mechanisms. The thrombogenic factors may be exogenous (e.g. trauma, surgery), endogenous (e.g. cancer, vascular diseases) or both (e.g. atherosclerosis, complicated pregnancy). Defects in the protective mechanisms may be congenital (e.g. factor V R506Q-mutation, deficiency of protein C, protein S or antithrombin) or acquired (e.g. lupus anticoagulans, deficiency of antithrombin in nephrosis). In recent years, research in thromboembolic diseases has been overwhelmed with new observations, rendering it worthwhile to put efforts into the evaluation of thrombotic mechanisms in individuals suffering from or predisposed to thromboembolic diseases. Such efforts will pave the way for more effective prophylaxis in thrombosis-prone patients, more specific treatment of thrombotic diseases, and the mastering of recurrent thrombosis.
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PMID:Thrombogenesis. 868 75

Vascular endothelium is strategically located at the interface between tissue and blood. It is pivotal for protecting against vascular injury and maintaining blood fluidity. Normal endothelium releases prostacyclin and nitric oxide, potent inhibitors of platelet and monocyte activation and vasodilators. Their syntheses are governed by isoforms of enzymes. Normal endothelial surface expresses ecto-adenosine diphosphatase, which degrades adenosine diphosphate and inhibits platelet aggregation; thrombomodulin, which serves as a binding site for thrombin to activate protein C; and heparin-like molecules, which serve as a cofactor for antithrombin III. Normal endothelium secretes tissue plasminogen activator, which activates the fibrinolysis system. Endothelium produces and secretes von Willebrand factor, which mediates platelet adhesion and shear-stress-induced aggregation. Injury to endothelium is accompanied by loss of protective molecules and expression of adhesive molecules, procoagulant activities, and mitogenic factors, leading to development of thrombosis, smooth muscle cell migration, and proliferation and atherosclerosis.
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PMID:Role of endothelium in thrombosis and hemostasis. 871 85

Diabetic patients have increased morbidity and mortality attributable to myocardial infarction, cerebrovascular disease and peripheral vascular disease, due to a high incidence of premature atherosclerosis. Abnormalities of hemostasis have been reported in many studies on diabetes over almost thirty years, but unfortunately the results have often appeared contradictory. The hemostatic alterations could lead to increased risk of vascular disease in diabetic patients. We have studied some coagulation factors (Fibrinogen, Factor II, Factor VII) and coagulation inhibitors (Protein C, Protein S), and plasminogen in fifty-four type 2 diabetic patients. The possible relationship between coagulation factors and coagulation inhibitors and parameters for glyco-metabolic control (glycosylated hemoglobin, fructosamine) and disturbed lipid metabolism (cholesterol, triglycerides) have ben analyzed. Our results show increase of fibrinogen, correlated with the metabolic control of the disease, positive correlation between plasminogen, factor II, protein S and hypertriglycerides, decreased levels of protein C correlated neither with metabolic control of disease neither with disturbed lipid metabolism.
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PMID:[Evaluation of the coagulation and fibrinolysis system in 54 patients with type 2 diabetes mellitus: correlations with lipid metabolism and blood glucose control]. 876 54

C4b binding protein (C4bp) is a regulator of the classical pathway of the complementing system. It forms a complex with protein S which serves as a cofactor of coagulation inhibitor, protein C. We have reported that C4bp is an acute phase reactant and associated with total cholesterol and triglyceride concentrations (Biochim. Biophys. Acta 963 (1988) 98-108). This suggests a possible association of C4bp with athero-sclerosis. We examined the relation of C4bp levels and the severity of atherosclerosis of the descending thoracic aorta in 98 Japanese men. The severity of aortic atherosclerosis was assessed by average sclerotic length (ASL) and average sclerotic area (ASA), using transesophageal echocardiography. After adjustment for age, C4bp levels increased significantly with increasing ASL and ASA. The association remained significant even after adjusting for total cholesterol, hypertension, smoking, drinking, body mass index, fasting blood sugar, and uric acid. Immunohistochemical analysis of specimens of the descending thoracic aorta from autopsies, demonstrated the presence of C4bp in the foamy macrophages of fatty streaks and the necrotic core of atheromatous plaque. These findings indicate that the serum level of C4bp can serve as an independent indicator of aortic athero-sclerosis.
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PMID:Relation of C4b-binding protein to athero-sclerosis of the descending thoracic aorta. 886 52

The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.
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PMID:Long-term treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults. 888 81

We identified a group of 24 young (less than 50 years of age) women with isolated, premature atherosclerotic aortoiliac occlusive disease and attempted to identify distinguishing hemostatic characteristics. Most of these patients (62%) presented with acute thromboembolic events (blue toe syndrome, n = 6; macroemboli, n = 6; or aortoiliac thrombosis, n = 3). Aortoiliac reconstruction (aortoiliac endarterectomy, n = 10, aortobifurcation bypass grafts, n = 6; and percutaneous angioplasty, n = 4) was complicated by early thrombosis in 6 of 20 cases (30%), (1 of 10 endarterectomies, 4 of 6 bypass grafts, and 1 of 4 angioplasties). Fresh thrombus overlying an atherosclerotic plaque was a common finding at surgery. This observation and the relatively high incidence of thromboembolic events led us to hypothesize that a characteristic hemostatic profile might underlie the remarkably similar clinical presentations of these women. Levels of antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant), plasminogen activator inhibitor-1, fibrinogen, antithrombin III, protein C, protein S, plasminogen, prothrombin fragment F1 + 2, and D-dimer were determined for these young women and for 21 age-matched white female control subjects without vascular disease and nine white male patients with aortoiliac occlusive disease (mean 61 years, range 43 to 74 years). The incidence of anticardiolipin antibodies was 42% (8 of 19) in the female patients, which was significantly elevated (p = 0.028). The female (62.5%) and male (100%) patients had significantly elevated D-dimer levels (p < 0.001). Deficiencies of antithrombin III, protein C, and protein S were rare. A unique pattern of premature aortoiliac atherosclerosis exists in some young women. Intra-arterial thromboembolic events are common at presentation and complicate surgical management. The role of antiphospholipid antibodies remains uncertain.
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PMID:Young women with advanced aortoiliac occlusive disease: new insights. 898 71

A comprehensive study on platelet aggregation, hemostasis, fibrinolysis and serum lipids in relation to peripheral serotonergic system has been performed on 41 nephrotic patients. Enhanced platelet aggregatory responses in both whole blood and in platelet rich plasma (PRP) were found upon stimulation with different agonists when compared to healthy volunteers. Increased levels of fibrinogen, fibrin monomers, and protein C activity were observed in nephrotic patients. Euglobulin clot lysis time was significantly prolonged in nephrotic patients. Activity of tissue plasminogen activator (tPA) inhibitor was higher in nephrotic syndrome, whereas tPA activity was significantly lower in these patients when compared to controls. Urokinase concentration, lipoprotein (a), cholesterol, LDL and VLDL levels were significantly higher in nephrotic patients over controls. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in nephrotic patients relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with nephrotic syndrome. Disequilibrium in the coagulolytic system, platelet hyperactivity, hyperfibrinogenemia, disturbances in peripheral serotonergic system together with lipid abnormalities may contribute to the progression and development of atherosclerosis and an enhanced risk of thromboembolic complications in nephrotic syndrome.
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PMID:Comprehensive study on platelet function, hemostasis, fibrinolysis, peripheral serotonergic system and serum lipids in nephrotic syndrome. 911 50


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