Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma from 14 patients with severe and diffuse coronary atherosclerosis has been compared with that obtained from a normal control group. While a decreased heparin-thrombin clotting time was demonstrated in the patient group, suggesting an increased level of circulating platelet factor 4, there was no significant alteration in plasma antithrombin III level. These results do not support a recent suggestion of a mild chronic intravascular coagulation in atherosclerosis.
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PMID:Heparin neutralizing activity (HNA) and antithrombin III in coronary artery disease. 57 15

Heparins are a heterogenous group of naturally occurring glycosaminoglycans characterized by anticoagulant activity and a wide range of molecular weights (low molecular weight or fractionated heparins evolving within the past two decades). Cofactors for endogenous inhibitors of coagulation (antithrombin III and heparin cofactor II), heparin administration results in a hypocoagulable state. Various platelet activities, including inhibition of activity induced by platelet-derived growth factors on vascular smooth muscle, also have been noted. Divorced of anticoagulant nature, novel applications may include a role in atherosclerosis prevention, acceleration of collateral coronary as well as peripheral circulation (i.e., angiogenesis), and continued (chronic) post-myocardial infarction therapy. Established indications include treatment of various thrombotic diseases, unstable angina, and thrombosis chemoprophylaxis in medical/surgical patients. The antithrombotic potential of the heparins is used also in thrombosis management related to extracorporeal circulatory assistance or dialysis devices. Heparin's therapeutic potential in the postphlebitic syndrome as well as in acute treatment of myocardial infarction (primarily and adjunctively with various thrombolytic agents) continues to undergo evaluation; however, early data review shows favorable trends for its inclusion in situations that favor thrombus generation (e.g., anterior myocardial infarction). Although associated with thrombocytopenia or hypertransaminasemia, the heparins are relatively well tolerated. In a small subset of patients, a severe thrombocytopenia may ensue, which generally resolves on medication withdrawal. As this class of glycosaminoglycans becomes better characterized, new indications may emerge for both native and the newer fractionated heparins.
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PMID:Pharmacodynamics, clinical indications, and adverse effects of heparin. 132 34

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estrogen-associated thromboembolism. 134 94

The Atherosclerosis Risk in Communities (ARIC) Study is an observational epidemiologic study conducted in four communities. ARIC has two major components: One records the occurrence of myocardial infarction resulting in hospitalization and coronary heart disease death in adults aged 35 to 74 living in the communities; the other is a prospective study of representative cohorts aged 45 to 64. Measurement of hemostatic factors is part of the cohort study, whose major objectives include investigating etiologic factors associated with atherosclerosis and its clinical outcomes. Arterial intimal-medial wall thickness, an index of early atherosclerosis, is measured precisely from ultrasound images of carotid and popliteal arteries. Participants (n = 15,801) completed their first examination, which included measurements of factors associated with coagulation (fibrinogen, factor VII, factor VIII, and von Willebrand factor) and coagulation inhibition (protein C and antithrombin III). Measures of coagulation activation, platelet activation, and fibrinolytic activity will be performed on stored plasma from selected case patients and control subjects.
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PMID:The Atherosclerosis Risk in Communities (ARIC) Study. Introduction and objectives of the hemostasis component. 134 97

Several population studies have shown that plasma levels of fibrinogen and factor VII are significantly associated with ischemic cardiovascular events. However, there is little information regarding the association of hemostatic factors with early atherosclerosis. To evaluate this, we compared the plasma concentrations of several coagulation proteins (fibrinogen, factor VII, factor VIII, von Willebrand factor, protein C, and antithrombin III) between 385 case patients, defined by high-resolution B-mode ultrasonography as having carotid arterial wall thickening, and 385 age-, race-, and sex-matched control subjects. These case patients and control subjects were selected from participants in a prospective population investigation, the Atherosclerosis Risk in Communities (ARIC) Study, who were examined between May 1987 and May 1989. Plasma fibrinogen, factor VII, protein C, and antithrombin III levels were significantly higher in case patients than in control subjects (P < 0.05). Factor VIII and von Willebrand factor were not different. These findings were supported by quartile distribution and univariate analysis. However, only fibrinogen remained significantly associated with carotid atherosclerosis on multivariate analysis taking other atherosclerosis risk factors into consideration. A one standard deviation increase in fibrinogen (67 mg/dL) was associated with a 1.6-fold increase in the odds of carotid atherosclerosis univariately (P < 0.001) and with a 1.3-fold increase in the odds multivariately (P = 0.010). Further analysis revealed that the association of fibrinogen with carotid atherosclerosis was somewhat stronger in cigarette smokers than in nonsmokers. This early case-control analysis of the ARIC Study demonstrates a significant association between plasma fibrinogen concentration and early atherosclerosis in the carotid arteries. In the context of published findings from population studies, our results indicate that plasma fibrinogen concentrations may be a useful marker for identifying individuals at high risk of developing arterial thrombotic disorders.
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PMID:Association of coagulation factors and inhibitors with carotid artery atherosclerosis. Early results of the Atherosclerosis Risk in Communities (ARIC) Study. 134 98

Recent epidemiologic studies found that there is a strong association of hemostatic factors with ischemic heart disease. The Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability (IIV) Study was conducted to estimate the various components of variation in hemostasis factors measured in the ARIC Study and to estimate the measures of repeatability of these factors. A total of 39 subjects (16 men, 23 women) were studied. Each had blood collected three times, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person (biologic) variability, and processing and assay variability were estimated. Then the reliability coefficient R was estimated as the proportion of total variance accounted for by between-person variance. The reliability coefficient can be interpreted as the correlation between measures made at repeat visits. Among the various analytes, the reliability coefficients were quite high for activated partial thromboplastin time and plasma factor VIII (R = 0.92, 0.86, respectively). Low repeatability was obtained for antithrombin III activity and protein C (R = 0.42, 0.56, respectively). The lack of repeatability for these variables derives mostly from the processing (field center and laboratory) variation. Other analytes--fibrinogen, plasma factor VII, and von Willebrand factor--were intermediate in repeatability. In comparing the analyte-specific high-level to low-level groups, no substantial difference of within-person plus method coefficient of variation between the two groups was found for any analyte except for factor VIII, whereas the corresponding variance components for most analytes were higher for the higher analyte level. Reliability coefficients from this ARIC IIV study are generally higher than those found in other studies, and this is related to the relative variations in populations studied and to the time between measurements.
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PMID:Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study. 134 24

We investigated heparin cofactor II (HC II) levels and their relationship to other haemostatic factors in the elderly in comparison with antithrombin III (AT III). We measured plasma HC II activity levels in 166 subjects aged from 61 to 99 years using a chromogenic method. HC II levels (94.4 +/- 18.5%) in the healthy elderly subjects were significantly (p less than 0.001) lower than in 40 healthy adult controls under 60 years of age (mean age: 51.5 years; 111.6 +/- 21.2%). HC II levels in the elderly subjects decreased further with age (r = 0.308, p less than 0.001) and the extent of the decrease was more marked than that for AT III (r = 0.179, p less than 0.05). There was no significant sex difference in HC II levels in the elderly. HC II levels correlated significantly with AT III levels and with acute phase reactants including sialic acid, fibrinogen, and PAI-1. HC II levels also correlated with factor VII, plasminogen, alpha 2-plasmin inhibitor, serum lipid, pseudocholinesterase, and albumin levels. These correlations were also found for AT III except active PAI-1 and tPA-PAI-1 complexes, but the correlations with acute phase reactants were stronger for HC II than AT III. We divided 154 elderly subjects into 4 groups by their pseudocholinesterase and albumin levels to estimate the effect of nutritional status on antithrombin activity in the elderly. HC II levels were normal in the elderly subjects with a good nutritional state (103 +/- 18%), but were significantly decreased in those with malnutrition (85 +/- 15%, p less than 0.001). AT III levels also showed the same tendency. These results indicate a decrease in the reserve capacity to inhibit thrombin generation at sites of atherosclerosis in response to trigger events. The deficiency of two major antithrombin factors in the elderly may indicate a tendency to thrombosis, especially in individuals with malnutrition. When considering the clinical significance of HC II, several other parameters, including age, nutritional status, hepatic synthetic ability, and the presence or absence of acute phase reaction should also be assessed.
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PMID:Heparin cofactor II deficiency in the elderly: comparison with antithrombin III. 138 49

Recent epidemiological studies have shown some beneficial health effects of the long chain (n-3) polyunsaturated fatty acids found in fatty fish. Although the results of these studies are often ambiguous and inconclusive, they have prompted many intervention trials to study the effects of n-3 fatty acids (FA) on the cardiovascular risk profile. However screening of the literature revealed that many of the beneficial effects of fish (oil) were obtained in intervention studies which had several serious shortcomings in their design. Therefore we started a placebo controlled randomised trial with increasing doses of n-3FA (respectively 0; 1.12; 2.24 and 3.37 g n-3 FA/day) and in order to have a maximum compliance this study was done in healthy monks. Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months. We couldn't detect any effect of n-3 FA supplementation on total cholesterol, HDL cholesterol, LDL cholesterol, apo A1, Lp(a), HbA1C, glucose, fibrinogen, factor VIII, antithrombin III, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor concentration, on bleeding time or on systolic or diastolic blood pressure. A pronounced significant dose dependent decrease of triglyceride levels was seen, while a slight but statistical significant decrease of apo B levels was observed in the highest fish oil dose. As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion, the clinical relevance of these finding is not clear at the moment. It seems therefore improbable that the anti-atherosclerotic action of n-3 FA is due to an effect on the lipid, apoprotein, coagulation or fibrinolysis parameters as measured in our study. Hence further research must be focused on other parameters (prostaglandins) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process.
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PMID:Influence of supplementation with N-3 fatty acids on different coronary risk factors in men--a placebo controlled study. 141 84

Cross-sectional associations between leukocyte count and sociodemographic and cardiovascular risk factors were investigated in 14,679 participants aged 45-64 years in the Atherosclerosis Risk in Communities Study carried out in four US communities in 1986-1989. Leukocyte count was strongly associated with present or past history of cigarette smoking and was higher in males than in females and in white subjects than in black subjects. Among never smokers, no sex differences were evident after adjustment for other risk factors. Race-associated differences were substantially reduced after other factors were taken into account in multivariate analyses. In never smokers, leukocyte count was higher in those who reported poor health, and it was inversely associated with high density lipoprotein cholesterol, forced expiratory volume at 1 second, physical activity, and, among whites, height and socioeconomic indicators. It was directly associated with indices of body weight and body fat, heart rate, blood pressure, hemoglobin, platelet count, uric acid, fasting insulin and glycemia, triglycerides, fibrinogen, antithrombin III, protein C, factors VII and VIII, and von Willebrand factor. The associations of leukocyte count with cardiovascular risk factors may either represent manifestation of subclinical disease or suggest that leukocyte count is part of the causal chain leading to atherosclerosis. Alternatively, the relation of leukocyte count to cardiovascular disease may be confounded by risk factors and thus be noncausal.
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PMID:Leukocyte count correlates in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. 144 16

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.
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PMID:Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery. 145 16


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