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

The plasma level of factor VII activity was a risk factor for the development of ischemic heart disease (IHD) in a prospective epidemiological study of hemostatic factors. We have previously reported significant correlations between factor VII clotting activity or antigen and lipid fractions in a group of 132 young men (< 30 years old) at low risk for IHD and concluded that control of the plasma factor VII level may be linked to lipid metabolism in normal male physiology. Because factor VII is one of four vitamin K-dependent procoagulant proteins, we hypothesized that plasma levels of all these proteins would be similarly controlled in normal physiology. In an extension of this study, we have measured two additional vitamin K-dependent clotting factors (prothrombin [factor II] and factor X activity), as well as factor VII activity and antigen and fasting serum lipid fractions in healthy young men and women (< 30 years old) at low risk for IHD. In the women, we found significant positive correlations of factor VII antigen with total or HDL cholesterol and of prothrombin or factor X with total or LDL cholesterol. In the men, factor VII activity or antigen correlated with total cholesterol, triglycerides, HDL cholesterol, or LDL cholesterol; prothrombin or factor X correlated with total cholesterol, triglycerides, or LDL cholesterol. In contrast, we found no significant correlations of fibrinogen with any of the lipid fractions in our groups of men or women. Our data support the hypothesis that control of the levels of the vitamin K-dependent procoagulant proteins is linked to lipid metabolism in the normal physiology of both men and women.
 ...
PMID:Correlation of vitamin K-dependent clotting factors with cholesterol and triglycerides in healthy young adults. 794 97

The relationship between thrombosis and atherosclerosis has been already suggested in the middle of the last century. More recently, in 1976 a hypothesis has been put forward which emphasize the leading role of chronic injury to endothelial cells followed by platelet attachment and the release of platelet derived growth factors in pathogenesis of atherosclerosis. There is also a growing body of evidence that cytokines, thrombin and the fibrinolytic system are involved in the initiation and progression of atherosclerotic lesions. Lipoprotein (a) is emerging as a link between atherogenic role of lipids and the haemostatic system. At the same time epidemiological data are pointing at the possible role of fibrinogen, factor VII and plasminogen activator inhibitor-1 as risk factors for ischemic heart disease. Thrombus formation is also responsible for the majority of acute coronary syndromes. On the other hand aspirin and other antiplatelet drugs seem to protect from vascular complications of atherosclerosis. Than the question which rather arises is: what is the best antithrombotic strategy in patients with cardiovascular diseases?
 ...
PMID:[Should hemostatic factors be considered in the prevention of cardiovascular disease?]. 797 94

Plasma prothrombin fragment F 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), fibrinogen and factor VII were related to variables associated with increased cardiovascular risk in 86 plasma donors (49 male and 37 female). F1 + 2 had a log-normal distribution and increased significantly with age and body mass index (BMI). Significantly, higher F1 + 2 levels were found in smoking compared with non-smoking males and in indolent males compared with males taking regular exercise. Higher levels were found in subjects with a parental history of ischaemic heart disease than in those lacking such a history. F1 + 2 correlated strongly with increasing cholesterol in males. Fibrinogen was significantly higher in male smokers than male non-smokers but did not vary with age or BMI. Factor VII correlated strongly with cholesterol and to a lesser extent with fibrinogen, F1 + 2 and BMI, but not with smoking. F1 + 2 correlated more closely with risk factors for cardiovascular disease than fibrinogen and factor VII, and consistently reflected the difference in cardiovascular risk when correlated with risk factors which have markedly different effects between the sexes. It promises to be a useful predictive marker of ischaemic heart disease.
 ...
PMID:Prothrombin fragment F1 + 2: correlations with cardiovascular risk factors. 807 5

Fibrinolytic activity (FA) was measured by dilute blood clot lysis time at entry to the Northwick Park Heart Study in 1382 white men aged 40-64, of whom 179 subsequently experienced episodes of ischaemic heart disease during a mean follow-up period of 16.1 years. There was a significant interaction between age and low FA (p = 0.02) with respect to ischaemic heart disease: a difference of one standard deviation in FA was associated with a difference of about 40% in ischaemic heart disease risk (p = 0.002) in those aged 40-54 at entry. The FA association remained after adjusting for plasma fibrinogen. High fibrinogen concentrations themselves were also associated with ischaemic heart disease, as was high factor VII activity with fatal events. Low FA in younger men may exert a long-term influence by impairing the removal of fibrin deposits that contribute to atherogenesis. Low FA appears to be a leading determinant of ischaemic heart disease in younger men and methods of enhancing fibrinolytic activity, whether by life-style changes or pharmacologically, should be considered.
 ...
PMID:Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. 790 83

Ischaemic heart disease, one of the major causes of death in the western world, seems to involve a complex interaction of haematological, biochemical, immunological, and physiological processes. Haematologically, the process involves alterations in the haemostatic mechanism as a result of elevations of certain clotting factors, particularly factor VII and fibrinogen, possibly as a result of increased fat consumption and smoking. Platelet hypersensitivity may also be related to immunological damage of the coronary endothelium and elevated fibrinogen levels. Cardiac surgery and heart transplantation remain the most effective methods for treatment of end-stage ischaemic heart disease. Surgical techniques are complex and necessitate the establishment of an extracorporeal blood circulation to bypass the functions of the heart and lungs, enabling the heart to be temporarily paralysed, and allowing surgery to be performed. Extracorporeal oxygenation and circulation of blood, and implantation of ventricular assist devices and artificial hearts, result in exposure of blood to foreign surfaces, leading to activation of the haemostatic mechanism and concomitant haemorrhagic/thrombotic complications. Heart and heart/lung transplantation require long-term regular monitoring of infection and rejection episodes in addition to control of bleeding complications sometimes experienced in the immediate post-operative period. Early identification of lymphoproliferative disorders which may arise as a result of excessive immunosuppression is also important. Implantation of artificial hearts and ventricular assist devices requires much more sophisticated haemostatic monitoring than routine cardiac surgery, in order to control the haemorrhagic/thrombotic complications so often associated with these procedures.
 ...
PMID:Ischaemic heart disease, cardiac surgery and heart/heart-lung transplantation reviewed from a haematological perspective. 824 37

An increase in factor VII was found to be a risk factor for ischemic heart disease. The present study was designed to test the hypothesis that this increase in factor VII is part of a general increase in vitamin K-dependent clotting factors. Initially, a prospective analysis of factor VII antigen and prothrombin activity was performed in two groups of young subjects without symptoms who differed in their risk of ischemic heart disease based on a history (or lack thereof) of premature heart disease in a first-degree relative. A statistically significant increase in prothrombin activity and factor VII antigen was found in the high-risk group of subjects when compared with the low-risk group. In a second series of subjects, factor IX and X activity assays were also performed, and all four of the vitamin K-dependent clotting factors were found to be significantly higher in high-risk subjects when compared with low-risk subjects. A second goal of the study was to explore whether correlations between factor VII and cholesterol and triglycerides might be due to binding of factor VII with apolipoprotein B. Although a significant correlation of factor VII antigen with apolipoprotein B (rho = 0.523, p < 0.025) was found in our high-risk group of subjects, the correlation between factor VII and triglycerides (rho = 0.641, p < 0.005) was even stronger statistically, suggesting a probable interaction of factor VII with very-low-density lipoproteins in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vitamin K-dependent clotting factors are elevated in young adults who have close relatives with ischemic heart disease. 824 91

Ischemic heart disease is caused by a combination of and interaction between a number of genetic and environmental factors. In a study of a group of healthy men from the United Kingdom, such an interaction was identified between the levels of plasma triglycerides and genetic variation determining plasma levels of factor VII, a clotting factor that is associated with risk of ischemic heart disease. We previously reported a common genetic polymorphism of the factor VII gene that changes arginine at residue 353 to a glutamine (Arg353-->Gln) and showed that healthy men who carry the allele for Gln353 had lower plasma levels of factor VII coagulant activity. This association is strongly confirmed in a new sample. Compared with 301 men with the allele for Arg353, 63 men with one or two alleles for Gln353 had levels of factor VII coagulant activity that were 20% lower (97.8% [95% confidence interval (CI), 95.2% to 100.4%] and 78.2% [CI, 73.8% to 82.9%], respectively; P < .0001), with similar genotype-associated differences observed for levels of factor VII antigen. The 6 men who were homozygous for the Gln353 allele had mean levels of factor VII coagulant activity and antigen that were lower by 40% and 50%, respectively. In an assay using bovine thromboplastin, which is specific for the cleaved (activated) form of factor VII, they had levels lower by 60%, suggesting that the major effect of the Gln353 substitution is to reduce the proportion of the circulating zymogen that is activated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Factor VII coagulant activity and antigen levels in healthy men are determined by interaction between factor VII genotype and plasma triglyceride concentration. 830 8

Although the majority of factor VII (FVII) circulates in the zymogen form, low levels of activated factor VII (FVIIa) have been postulated to exist in plasma and to serve a priming function for triggering of the clotting cascade. However, direct measurement of plasma FVIIa has not previously been possible. We have quantified plasma FVIIa levels using a novel, highly sensitive assay that is free from interference by FVII. Specificity of this clot-based assay results from the use of a mutant tissue factor that is selectively deficient in promoting FVII activation, but retains FVIIa cofactor function. In normal adults, FVIIa was found to be present in plasma (mean: 3.6 ng/mL) with considerable variation between individuals (range: 0.5 to 8.4 ng/mL). FVIIa levels were only loosely correlated with FVII coagulant activity, but were elevated in pregnancy and reduced with oral anticoagulant therapy. Incubation of plasma on ice in glass containers (cold activation) resulted in substantial FVIIa generation. Measurement of plasma forms of factor VII is of potential clinical importance because elevated FVII coagulant activity has been implicated as a significant risk predictor for ischemic heart disease. Clinically, this new assay will now permit direct assessment of the role of plasma FVIIa in thrombotic disorders.
 ...
PMID:Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. 842 65

Several epidemiological studies have found that the plasma fibrinogen level is a risk factor for ischemic heart disease (IHD), similar in importance to the serum cholesterol level. A family history of IHD is also a significant risk factor for IHD, statistically independent of the serum cholesterol level. Whether the familial risk for IHD is related to genetic control of the fibrinogen level is unknown. Estimates of the genetic contribution to the variance in plasma fibrinogen levels vary markedly. We previously found elevated levels of cholesterol and factor VII in young subjects with a familial history of premature IHD. In the present study we chose to measure fibrinogen, factor VII antigen, and total cholesterol levels in 43 asymptomatic first-degree relatives (< 50 years old) of patients with premature IHD and in 43 age- and sex-matched asymptomatic young adults at low risk of IHD. No subjects in either group were smokers. The mean plasma fibrinogen level of the high-risk group (259 mg/dL) did not differ significantly from that of the low-risk group (250 mg/dL; p > 0.4). In contrast, the high-risk group had significantly higher mean factor VII antigen (p < 0.001) and mean serum cholesterol (p < 0.0001) than the low-risk group. These data argue against the hypothesis that genetic determination of the plasma fibrinogen level is a common pathophysiological mechanism responsible for familial risk of IHD.
 ...
PMID:Plasma fibrinogen level is not elevated in young adults from families with premature ischemic heart disease. 849 99

Factor VII (FVII) is a plasma vitamin K-dependent glycoprotein that plays an important role in the initiation of tissue factor-induced coagulation (extrinsic pathway of blood coagulation). An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. Recently, the coagulation assay using soluble tissue factor(sTF) enables us to measure the plasma levels of the activated form of factor VII(FVIIa) without the effect of the FVII zymogen form. We have developed the fluorogenic assay for FVIIa using sTF and measured the plasma FVIIa in atherosclerotic diseases. The FVIIa level in the Japanese was lower than that reported in Caucasians, suggesting that the incidence of ishemic heart disease is lower in the former. The FVIIa level was higher in the patients with cardiovascular diseases (ischemic heart disease and cerebral infarction), non-insulin-dependent diabetic mellitus, hypertension with microalbuminuria, and renal failure than in the healthy controls. The FVIIa levels were also increased in non-insulin-dependent diabetic patients, and this FVIIa increase was positively correlated with urinary albumin excretion. Furthermore, FVIIa levels were not correlated with the levels of lipids and the activity of hepatic synthesis, indicating that FVIIa may be an independent risk factor for cardiovascular disease.
 ...
PMID:[Activated factor VII as a new cardiovascular risk factor of atherothrombotic disease]. 856 29


<< Previous 1 2 3 4 5 6 7 Next >>