Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was only quite recently that the thrombotic component in myocardial infarction and sudden coronary death was generally acknowledged. When attention was eventually paid to it, interest initially centered primarily on platelet function. There is, of course, no doubt about the central role of platelet adhesion and aggregation in thrombogenesis, but still no generally accepted measure of platelet function has been shown to be associated with the later onset of ischemic heart disease (IHD). Epidemiologically, the assessment of coagulability has been more rewarding. Several prospective studies have now shown a strong relationship between the plasma fibrinogen level and the incidence of IHD and stroke. Epidemiologic and laboratory studies have also implicated factor VII and extrinsic pathway activity in the onset of IHD. Other components of the hemostatic system that are probably involved include factor VIII activity and the fibrinolytic system. It is increasingly clear that lipoproteins exert a major influence on coagulability as well as their better known role in atherogenesis. Any further polarization of hypotheses for IHD as being purely atherogenic or purely thrombogenic is therefore counterproductive. At the same time, antithrombotic measures for primary prevention need to be evaluated as thoroughly as lipid-lowering regimens. If thrombosis is seen as the final arterial event in virtually all major episodes of IHD, the indications for antithrombotic agents in primary prevention may be wider than those for lipid-lowering regimens. It is therefore necessary to establish as quickly as possible not only the preventive effectiveness of antithrombotic measures, including low-dose aspirin and low-intensity oral anticoagulation, but also the relative effectiveness and safety of antithrombotic and lipid-modifying regimens.
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PMID:Thrombosis and cardiovascular disease. 134 86

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

Haemostatic changes may explain the paradoxical observations that regular exercise helps to prevent ischaemic heart disease but the risk of myocardial infarction and sudden death is actually increased during exercise. This study measured relevant haemostatic variables in 100 athletes before and after races of 10-26.2 miles duration and compared resting levels in athletes with 25 non-exercising controls. Prothrombin time, kaolin cephalin clotting time, fibrinogen, factor VII, factor VIII clotting (one and two stage), von Willebrand factor antigen, euglobulin clot lysis time, fibrin degradation products, full blood count, mean platelet volume, and platelet aggregation to collagen, adrenalin and adenosine diphosphate were measured. The immediate post-race results showed the familiar rise in platelet count and factor VIII clotting but there was no evidence of consumption or thrombin modification of factor VIII clotting. Platelet aggregation to adrenalin was reduced after the race and fibrinolysis was increased (P less than 0.05). The athletes at rest showed no significant differences from controls in their coagulation factor levels but showed increased fibrinolytic activity and reduced platelet aggregation to adrenalin (P less than 0.05). These results suggest a hypocoagulable rather than a hypercoagulable state during running and are consistent with the epidemiological evidence that such exercise is beneficial in the prevention of ischaemic heart disease.
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PMID:Haemostatic changes in long-distance runners and their relevance to the prevention of ischaemic heart disease. 189 55

The role of factor VII in the haemostatic mechanism as well as thrombosis has recently gained new interest. Today's concept that factor VII may be a key regulator in the initiation of blood coagulation is based on studies that provide new evidence for a mandatory activation of factor VII to factor VIIa in blood. Exposure of thromboplastin to the circulation may not trigger activation of blood coagulation before the one chain factor VII is converted to the active two chain form of factor VIIa. A hypothetical model is proposed for the initiation and subsequent activation steps of the blood coagulation process. In this model, it is suggested that circulating activators of factor VII activate inactive complexes of thromboplastin-factor VII. Subsequently, newly generated factor Xa will accelerate this reaction and thereafter be the most potent activator of factor VII. This model would also fit with the clinical observation that moderate factor VII deficiency may be associated with thrombotic episodes discussed in this communication. This article also discusses the role of recombinant factor VIIa in the treatment of factor VIII deficiency patients with acquired factor VIII inhibitors, factor VII and ischemic heart disease and the factor VII-phospholipid complex, and the regulation of the thromboplastin-factor VIIa complex by factor Xa and extrinsic pathway inhibitor (EPI).
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PMID:Factor VII and haemostasis. 213 55

We conducted a prospective study of serial intravenous digital subtraction angiography to determine the relation of arterial disease risk factors and hemostatic variables with the presence of visible atheroma at the carotid bifurcation. Of the 492 patients with cerebrovascular disease or ischemic heart disease who entered the study, 354 had hematologic studies, including platelet aggregation in 230. Abnormal angiograms were associated with greater age, treated hypertension, current smoking, and lower hemoglobin levels but with higher uric acid, factor VIII, and fibrinogen concentrations. In patients presenting with isolated transient ischemic attacks, abnormal angiograms were also associated with higher levels of cholesterol and triglycerides. To study atheroma progression, the 230 patients with complete data at entry were recalled 2 years later. Repeat angiography in 209 patients showed progression of visible bifurcation disease in 13.4%. There was some evidence that progression was linked to higher age, hypertension, and more severe disease at entry, but further analysis was hampered by the small number of patients showing increased plaque size. The possible role of risk factors and hemostatic variables, especially fibrinogen, is discussed. Factors that did not correlate with progression of angiographically visible disease may also influence clinical end points by other mechanisms, such as thrombogenesis.
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PMID:Arterial disease risk factors and angiographic evidence of atheroma of the carotid artery. 236 11

Platelet aggregability and plasma factor VIII-related antigen (F. VIIIR:AG) level in 16 ischemic heart disease (IHD) patients were increased by isometric exercise and these changes were prevented by administration of a lipid lowering agent, simfibrate, a derivative of clofibrate. Serum total cholesterol (TC) level decreased and the high density lipoprotein-cholesterol (HDL-C)/TC ratio increased with the treatment. Another 7 hyperlipidemics were administered with simfibrate. Platelet malondialdehyde (MDA) production decreased with improvement in lipid profile. In an in vitro study, platelet aggregability and the plasma level of von Willebrand factor (vWF) and F.VIIIR:AG of normal citrated blood were increased by passing it through a glass bead column. Combining above results of the three separate studies, it would be suggested that hyperlipidemia might enhance platelet activation in vivo, which occurred through contact of platelets to atherosclerotic rough vessel surface. The anti-platelet effect of simfibrate might be mediated through its effect on arachidonic pathway in platelets.
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PMID:Influence of lipids metabolism on platelet activation in vivo. 641 24

General recognition of the thrombotic component in ischaemic heart disease (IHD) is comparatively recent. Despite the obvious role of platelets, it has in many ways--and certainly epidemiologically--been work on the coagulation system that has been more rewarding in characterising those at high risk of IHD on account of haemostatic abnormalities. Raised plasma fibrinogen levels are clearly and independently associated with the onset of both clinically manifest IHD and stroke and probably with lower extremity arterial disease as well. High fibrinogen levels also increase recurrence rates and the progression of these conditions. High factor VII activity levels are associated with increased mortality from IHD but not with non-fatal episodes. Low fibrinolytic activity and raised factor VIII levels are also associated with increased IHD incidence. High fibrinogen levels predispose to thrombosis by effects on viscosity, platelet aggregability, fibrin deposition and the atherogenic process. There is increasing evidence that raised factor VII activity levels lead to increased thrombin production. Associations of several personal characteristics--notably smoking in the case of fibrinogen and dietary fat intake in the case of factor VII activity--influence the coagulation system in ways that are likely to predispose to thrombosis. Besides well known agents such as aspirin and anticoagulants, increasing attention ought now to be given to the antithrombotic potential of fibrinogen-lowering agents.
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PMID:Haemostatic function and arterial disease. 780 29

Relations of factor VIII activity, FVIIIC, and von Willebrand factor antigen (vWFAg), with ischaemic heart disease (IHD) were examined in 1393 men aged between 40 and 64 years at entry to the Northwick Park Heart Study (NPHS) who experienced 178 first major episodes of IHD during an average follow-up period of 16.1 years. After allowing for the large factor VIII differences between the main ABO blood groups, FVIIIC was probably associated with IHD incidence, possibly more strongly with fatal than non-fatal episodes. Thus, an increase of 1 standard deviation in FVIIIC raised the risk of fatal IHD by about 28%. vWFAg was also significantly associated with fatal events. The observed relation of FVIIIC with IHD incidence probably underestimates the true strength of the association because of the considerable within-person and laboratory variability in factor VIII measurements. FVIIIC and vWFAg were strongly correlated (r = 0.57) and in statistical terms there may be little to choose between them in long-term studies of IHD. Taking account of evidence that haemophiliacs seem to experience less IHD than expected, high factor VIII levels may contribute to the incidence of IHD by increasing thrombogenic potential. The incidence of IHD was significantly higher in those of blood group AB than in those of groups O, A or B, particularly for fatal events. There was no evidence that the FVIIIC and vWFAg associations with IHD are determined by ABO group. The factor VIII and ABO blood group effects therefore appeared to be independent. Group AB may be a genetic marker of characteristics influencing other indices of IHD risk such as short stature, NPHS men (though not women) of group AB being about 2 cm shorter than those of other groups.
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PMID:Factor VIII, ABO blood group and the incidence of ischaemic heart disease. 781 72

An increased risk of ischemic heart disease has been reported in men with the Lewis blood group phenotype Le(a-b-). We have investigated the relationship between Lewis phenotype and cardiovascular risk factors in 1714 participants in the Coronary Artery Risk Development in Young Adults Study, an ongoing investigation on life-styles and evolution of cardiovascular risk factors. No significant differences were observed among Lewis phenotypes for body mass index, blood lipid levels, blood pressure, or clotting factors VII and fibrinogen. However, in white men with blood groups A, B, or AB, and the Le(a-b-) phenotype, significantly higher levels of factor VIII (p < 0.01) and von Willebrand factor (p < 0.03) were observed than in those with other Lewis phenotypes (Le[a+b-] or Le[a-b+]). Two-way analysis of variance indicated a significant interaction between blood group and Lewis phenotype (p = 0.0053) in terms of relationship to factor VIII. A similar trend was observed in black men with blood type A, B, or AB, and phenotype Le(a-b-) for factor VII/von Willebrand factor and in women with blood type A, B, or AB, and phenotype Le(a-b-) for factor VIII. Our data suggest that the Le(a-b-) phenotype and blood groups A, B, and AB, by virtue of their association with raised levels of factor VIII and von Willebrand factor, may be risk markers for future atherothrombotic disease.
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PMID:Relationship among Lewis phenotype, clotting factors, and other cardiovascular risk factors in young adults. 859 91

The Northwick Park Heart Study suggested that factor VII activity might be more strongly related to fatal than non-fatal events of ischaemic heart disease. We used polychotomous logistic regression to model simultaneously the probabilities of fatal events, non-fatal myocardial infarction, dying of causes other than ischaemic heart disease and of events, non-fatal myocardial infarction, dying of causes other than ischaemic heart disease and of event-free survival. We followed 1459 white men aged 40-64 at recruitment for a mean period of 16.1 years. Of these, 92 died of ischaemic heart disease, 100 experienced non-fatal myocardial infarction, 173 died of other causes, and 1094 men were alive. Factor VII activity was strongly related to fatal events of ischaemic heart disease but not to non-fatal events (p = 0.008). A difference of 1 SD in factor VII activity was associated with a difference of nearly 50% in the probability of dying of ischaemic heart disease, but with no difference for non-fatal myocardial infarction. This contrast was not seen for smoking, cholesterol, blood pressure, fibrinogen or factor VIII activity. High levels of VII activity may influence outcome at the time of plaque rupture and tissue factor release by enhancing thrombin production and thus fibrin deposition and platelet aggregability. The apparently differential effect of factor VII activity on fatal and non-fatal ischaemic heart disease may have important screening and prophylactic implications.
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PMID:Factor-VII activity and ischaemic heart disease: fatal and non-fatal events. 792 91


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