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)

The Northwick Park Heart Study found that factor VII (FVII) activity was a risk factor for ischemic heart disease, and other studies based on indirect assays of activated factor VII (FVIIa) found an elevation of FVIIa postprandially. We hypothesized that postprandial elevation of FVIIa would produce intermittent activation of factor X to Xa and, subsequently, prothrombin to thrombin. We chose to study postprandial activation of coagulation with a new assay specific for FVIIa that uses soluble tissue factor and with a prothrombin fragment 1 + 2 (F1 + 2) assay to detect the activation of prothrombin by factor Xa. We fed a high-fat breakfast (30 g/m2) to 30 healthy volunteer subjects (30.8 +/- 9.8 years; range, 20 to 49 years) on no medication. Fasting blood samples were collected for FVIIa, FVII antigen (FVIIag). and F1 + 2 as well as triglycerides and total and HDL cholesterol. A significant difference was found between fasting (2.82 +/- 1.49 ng/mL. mean +/- SD) and 6-hour postprandial (3.45 +/- 2.08 ng/mL) FVIIa levels (P < .004); FVIIag did not change significantly (mean, 0.89 U/mL fasting and 0.90 U/mL at 6 hours). In contrast, F1 + 2 levels were slightly lower 6 hours postprandially than fasting (median, 0.39 versus 0.44 nmol/L, P < .02). Four-hour postprandial triglyceride levels correlated significantly (p = 0.51, P < .02) with 6-hour postprandial FVIIag but not with 6-hour postprandial FVIIa. Postprandial F1 + 2 levels (at 6 hours) correlated significantly (p = 0.39, P < .04) with fasting FVIIag levels but not with 6-hour postprandial FVIIa levels. Thus, the basal FVIIag level, in the fasting state, may be involved in control of the generation of F1 + 2. We found a postprandial increase in FVIIa levels after a dietary fat load but did not find a concomitant postprandial burst of activation of factor X and prothrombin as measured by F1 + 2. Further studies are to test whether postprandial FVIIa generation leads to enhanced activation of coagulation.
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PMID:Postprandial elevation of activated factor VII in young adults. 891 Dec 70

We cross-sectionally measured plasminogen activator inhibitor-1 (PAI-1) activity, fibrinogen, factor VII (FVII:C) and VIII (FVIII:C) coagulant activity, and von Willebrand factor antigen (VWF:Ag) in 162 traditional horticulturalists older than 40 years from the tropical island of Kitava, Papua New Guinea, where the intake of western food is negligible and where stroke and ischaemic heart disease appear to be absent. Identical analyses were made in Swedish subjects of comparable ages. Kitavams had markedly lower PAI-1 activity, with 85% of males and 100% of females having PAI-1 activity < or = 5 U/ml, as compared with 22 and 14% in Swedish males and females (p < 0.0001). Surprisingly, Kitavans also had higher FVII:C. FVIII:C and VWF:Ag. Fibrinogen was 10% lower in Kitavan males while 25% higher in Kitavan females. The very low PAI-1 activity in Kitavans may explain some of their apparent freedom from cardiovascular disease and probably relates to their extreme leanness.
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PMID:Haemostatic variables in Pacific Islanders apparently free from stroke and ischaemic heart disease--the Kitava Study. 903 56

Considerable evidence suggests that a high concentration of coagulation factor VII is a risk factor for ischemic heart disease. Factor VII is known to be influenced by dietary fat and probably by dietary fiber in young and middle-aged people. There are no data available in elderly people and the effects of different types of fat are unclear. This study examines the relation of factor VII activity (factor VIIc) with dietary fat and fiber in The Rotterdam Study. The Rotterdam Study is a population-based study among 7983 men and women aged > or = 55 y. Factor VIIc was measured in 3007 subjects (1730 women and 1277 men aged 67.3 +/- 7.8 and 66.3 +/- 7.0 y, respectively). Measurements included cardiovascular risk factors and habitual diet was assessed by a semiquantitative food-frequency questionnaire. Associations that were significant or nearly significant differed for some nutrients between men and women. Total fat intake showed a direct association with factor VIIc only in women (beta = 0.1%/g; 95% CI: 0.01, 0.20). Saturated fat intake was associated with factor VIIc in women (beta = 0.18%/g; 95% CI: 0.001, 0.36) and in men (beta = 0.11%/g; 95% CI: -0.06, 0.27). Monounsaturated fat was positively related to factor VIIc in women (beta = 0.17%/g; 95% CI: -0.05, 0.39) and polyunsaturated fat was inversely associated with factor VIIc in men (beta = -0.15%/g; 95% CI: -0.33, 0.03). Fiber intake was inversely associated with factor VIIc in both men (beta = -0.31%/g; 95% CI: -0.57, -0.06) and women (beta = -0.36%/g; 95% CI: -0.63, -0.09). No associations were found for energy intake. In elderly persons, factor VIIc is associated with fat and fiber intake. This suggests that factor VIIc is influenced by nutritional factors, even in old age.
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PMID:The association of dietary fat and fiber with coagulation factor VII in the elderly: the Rotterdam Study. 906 22

Although hormone replacement therapy (HRT) appears to protect women from ischaemic heart disease (IHD), its use is associated with increased factor clotting activity (VIIc), an independent risk factor for IHD. The nature of this factor VII rise was therefore examined in a cross-sectional study of 279 women aged between 40 and 65 years. Ninety-four were pre-menopausal, 44 were post-menopausal and taking HRT, whilst 141 were post-menopausal non-users. For those women on oestrogen-only HRT, the mean factor VIIc was 144%, compared to 130% for post-menopausal non-users, and 116% for those on combined HRT. These differences were significant (p = 0.01). Oestrogen-only users also had significantly higher mean levels of factor VIIa (3.3 ng/ml) compared to non-users (2.2 ng/ml) and those on oestrogen-progestogen HRT (2.2 ng/ml-p = 0.015). In contrast for factor VII antigen the mean values of the three groups were similar. Analysis of the age-regression slopes showed a significant age-related rise in factor VIIc of 1.2% per annum (p < 0.01) for post-menopausal non-users. There was a similar increase in factor VII antigen (2.1%) but no rise in factor VIIa. For all HRT users there was no change with age for any of the factor VII measures. Thus the age-related rise in factor VIIc appears to be due to an increase in factor VII zymogen alone, and taking HRT seems to abolish such a rise. In contrast, the increased factor VIIc seen with oestrogen-only HRT appears to be secondary to factor VII activation.
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PMID:The effect of hormone replacement therapy of the age-related rise of factor VIIc, and its activity state. 910 38

This study examined cross-sectional age relations of blood pressure, anthropometric indexes, serum lipids, and hemostatic variables in 203 subsistence horticulturists aged 20-86 y in Kitava, Trobriand Islands, Papua New Guinea. The population is characterized by extreme leanness (despite food abundance), low blood pressure, low plasma plasminogen activator inhibitor 1 activity, and rarity of cardiovascular disease. Tubers, fruit, fish, and coconut are dietary staples whereas dairy products, refined fat and sugar, cereals, and alcohol are absent and salt intake is low. Although diastolic blood pressure was not associated with age in Kitavans, systolic blood pressure increased linearly after 50 y of age in both sexes. Body mass index decreased with age in both sexes. Serum total cholesterol, triacylglycerol, low-density-lipoprotein cholesterol, and apolipoprotein B increased in males between 20 and 50 y of age, whereas high-density-lipoprotein cholesterol and apolipoprotein A-I decreased. There were no significant differences in these indexes with age in the few females studied. A slight linear age-related increase of lipoprotein(a) was present in males. Plasma fibrinogen, factor VII clotting activity, factor VIII clotting activity, and von Willebrand factor antigen increased with age in both sexes but plasminogen activator inhibitor 1 activity did not. The modest or absent relations between the indexes measured and age are apparently important explanations of the virtual nonexistence of stroke and ischemic heart disease in Kitava.
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PMID:Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study. 932 59

Increased plasma factor VII coagulant activity (FVII:C) has been associated with the risk of ischemic heart disease (IHD). Differences in plasma FVII:C among individuals are associated with three common polymorphisms in the FVII gene. Therefore, we investigated FVII polymorphisms in four populations that differ in their risk of developing cardiovascular disease, namely, Europeans, Greenland Inuit, Gujarati Indians, and Afrocaribbeans. We studied (1) the promoter polymorphism, which is the result of a decanucleotide insertion in the FVII promoter at position -323 from the start of translation; (2) the hypervariable region 4 polymorphism (HVR4), which is the result of a variable number of tandem repeats in intron 7; and (3) the RQ353 polymorphism, a guanine-to-adenine substitution in the position of the codon for amino acid 353 resulting in an amino acid replacement of arginine (R) by glutamine (Q) in the FVII protein. The frequencies of these three polymorphisms and their linkage disequilibrium were different in the four populations studied. The frequencies of the alleles associated with higher plasma FVII:C were lower in the Europeans than in the Inuit, a population with a lower incidence of IHD. There was an association between both the promoter polymorphism and the RQ353 polymorphism and the plasma FVII:C in the Europeans, the Inuit, and the Gujarati Indians, and an association only between the RQ353 polymorphism and plasma FVII:C in the Afrocaribbeans. Only in the Inuit was the HVR4 polymorphism associated with plasma FVII:C. In multiple regression analysis, the additional information provided by the promoter polymorphism when the other polymorphisms were already included in the model was the most pronounced, suggesting that the promoter polymorphism may be the functional mutation having the greatest effect on determining plasma FVII:C.
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PMID:Factor VII polymorphisms in populations with different risks of cardiovascular disease. 935 54

Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).
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PMID:Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. 940 28

We carried out a case-control study to determine whether von Willebrand factor (vWF) antigen (and factor VII and tissue plasminogen activator [tPA] antigens) are associated with ischemic stroke. Ninety-five patients with transient ischemic attack or minor ischemic stroke recruited from the Oxfordshire Community Stroke Project and one neurology clinic were compared with 236 controls, group-matched for age and sex, from the same general practitioners as the incident cases. In crude analyses, concentrations of vWF antigen were significantly higher in cases than in controls (p = 0.004). The age- and sex-adjusted odds ratios from lowest (referent) to highest quartile of vWF antigen were 1.00, 1.15, 2.34, and 2.36 (trend test, p = 0.006). Factor VII antigen and tPA antigen were not significantly different between cases and controls. Although adjustment for other potential risk factors abolished the statistical significance of the association between vWF and disease, this was largely due to the influence of history of ischemic heart disease. We conclude that vWF is a potent and independent risk factor for transient ischemic attack, minor ischemic stroke, and, by extrapolation, ischemic stroke in general. The data also suggest that vWF may be a risk factor for both ischemic stroke and ischemic heart disease. We found no evidence to implicate factor VII and tPA as risk factors for ischemic stroke.
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PMID:Von Willebrand factor and risk of ischemic stroke. 940 45

Total dietary fat intake is an important determinant of factor VII coagulant activity, a hemostatic risk factor for fatal ischemic heart disease in middle-aged men. This association has a long-term effect by which a high-fat diet increases plasma factor VII antigen concentration, and an acute effect whereby a small proportion of factor VII is converted from its proenzyme to active serine protease for several hours postprandially. In adults whose usual diet is rich in long-chain saturated fatty acids, postprandial activation of factor VII occurs irrespective of the fatty acid composition. The underlying mechanism appears to require lipolysis and the presence of another coagulant protein, factor IX. There is limited evidence that factor VII activation after a meal rich in polyunsaturated fatty acid is blunted when the background diet also has a high content of polyunsaturated fatty acid. Meals rich in medium-chain triacylglycerols do not induce factor VII activation. The effects of dietary enrichment with n-3 fatty acids on factor VII are uncertain. All studies have been confined to the fasting state, and only one suggested changes consistent with factor VII activation. Fibrinogen concentration, another major hemostatic risk factor for ischemic heart disease, is uninfluenced by dietary fat content or composition, the one exception being inconsistent reports of a reduction after dietary enrichment with n-3 fatty acids. Overall, the evidence so far indicates that total dietary fat intake is more important than dietary fat composition for factor VII and by implication its attendant risk of fatal ischemic heart disease in high-risk populations.
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PMID:Effects of diet composition on coagulation pathways. 949 67

Obstructive sleep apnoea syndrome (OSAS) is a very common disorder. Patients with OSAS are at an increased risk for cardiovascular events. It has also been reported that a 25% rise in factor VII clotting activity (FVIIc) is associated with a 55% increase in ischaemic heart disease death during the first 5 years. We examined the effects of nasal continuous positive airway pressure (NCPAP) treatment on FVIIc in patients with OSAS. FVIIc was investigated prospectively in 15 patients with OSAS before (mean +/- SEM apnoea and hypopnoea index (AHI) 61.5 +/- 4.2 and after (AHI 3.0 +/- 0.9) NCPAP treatment for immediate relief, at 1 month after treatment and at over 6 months. FVIIc levels gradually decreased after NCPAP treatment. After 6 months of NCPAP treatment, FVIIc levels had decreased significantly (before 141.1 +/- 11.7% vs. after 6 months 110.7 +/- 6.2%; p < 0.01). Six of the seven patients whose FVIIc levels were over 140% before the NCPAP treatment had FVIIc levels below 130% after 6 months or 1 year of NCPAP treatment. This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients. If patients, especially obese ones, present with high FVIIc of unknown origin, it would be prudent to check for OSAS.
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PMID:Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome. 1002 17


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