UMLS:C0007222 - FACTA Search

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Query: UMLS:C0007222 (cardiovascular disease)
65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100. 5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.
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PMID:Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study. 1066 60

This year's work on hormone replacement therapy (HRT) and cardiovascular disease has been remarkable for the publication of the first randomised controlled trial of HRT use, the Heart Estrogen Replacement Study (HERS). The findings go against not only the trend of previous observational epidemiological studies, but also against findings in the very many studies which have previously shown and continue to show this year a beneficial effect of HRT on a large variety of cardiovascular risk factors, including endothelial function, here reviewed. The aspect of the effect of HRT on clotting variables is clearly crucial given the increased risk of venous thrombosis, and also increased number of cardiac events in the first 4 months of the HERS. Prothrombotic factors increase with age in women, and HRT alters these, particularly fibrinogen, factor VII, and PAI (less change with transdermal HRT) and antithrombin III. In normal women therefore the balance should be towards fibrinolysis rather than coagulation. Work has been presented in abstract for clarifying the effects of HRT on coagulation markers and grasping the problem of differences according to its route of administration. The full publications on this work are expected shortly. We are still awaiting evidence from randomized controlled trials of HRT in primary prevention; one is now recruited but will not report until 2005.
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PMID:Hormone replacement therapy and cardiovascular disease. 1068 52

Epidemiological data suggest that the use of oestrogen replacement therapy (ERT) and combined oestrogen/progestagen replacement therapy (HRT) in healthy postmenopausal women is associated with a decreased risk of cardiovascular events. In sharp contrast, the HERS study, a secondary prevention trial in postmenopausal women with established coronary heart disease, did not show a favourable effect, with a trend towards an increased risk of cardiovascular disease in the first year of treatment. This paper provides an overview of randomised, controlled trials (RCTs) in postmenopausal women published in the literature and discusses possible explanations for the contrast between data from the epidemiological studies and the results of the HERS study. ERT and HRT are associated with: 1) an improved lipid profile; and 2) a decrease in homocysteine and endothelin levels. Data on factor VII and fibrinogen were not consistent. There were insufficient data on the effects on blood pressure, glucose metabolism, vasomotor regulation, arterial stiffness, thrombomodulin, adhesion molecules, and clotting and fibrinolysis, as well as on the effects of route of administration and the role of progestagens. Finally, endothelium-dependent vasodilatation appears to increase with ERT, but the effects of HRT are less clear This paucity of controlled data indicates that, although ERT and HRT improve surrogate measures of risk of atherothrombosis, adverse effects of ERT and HRT on biological mechanisms related to risk of atherothrombosis can by no means be excluded.
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PMID:Cardiovascular disease risk and hormone replacement therapy (HRT): a review based on randomised, controlled studies in postmenopausal women. 1070 21

Recently, an association has been found between factor VII polymorphisms and the risk of familial myocardial infarction. To obtain a thorough evaluation of the influence of factor VII gene on the risk of myocardial infarction, we extended our analysis to the role of a decanucleotide insertion/deletion functional polymorphism (-323 0/10-bp) in the promoter region of factor VII and to possible interactions with the HVR4 intron polymorphism. We performed a case-control study of 176 patients with myocardial infarction, over 45 years, who had a familial history of arterial thrombosis and 227 control subjects without a personal or family history of cardiovascular disease. The frequency of the rare allele of 10 bp was lower in cases (0.14 95% CI, 0.10-0.17) than in controls (0.19 95% CI, 0.16-0.23; chi(2)=4.7, p=0.03). Allowing for Hardy-Weinberg equilibrium in controls and testing for association under restricted maximisation, there was a significant difference in genotype frequency between cases and controls (p=0.02). Carriers of the 10-bp allele had an odds ratio for myocardial infarction of 0.65 (95% CI, 0.37-1.12), in multivariate logistic regression analysis. Combination analysis of -323 0/10-bp and HVR4 polymorphisms shows half reduction in the risk of myocardial infarction in comparison with the reference group for all the other groups, suggesting that there was no additivity between the effect of the 10-bp and the H7 alleles. Our findings suggest that the promoter polymorphism of factor VII gene may influence the risk of familial myocardial infarction.
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PMID:The decanucleotide insertion/deletion polymorphism in the promoter region of the coagulation factor VII gene and the risk of familial myocardial infarction. 1070 29

Previous studies have established that factor VII gene (F7) polymorphisms (5'F7 and R353Q) contribute about one-third of factor VII (FVII) level variation in plasma. However, F7 genotyping in patients with cardiovascular disease has produced conflicting results. Population and expression studies were used to investigate the role of intron 7 (IVS7 ) polymorphisms, including repeat and sequence variations, in controlling activated FVII (FVIIa) and antigen (FVIIag) levels. Genotype-phenotype studies performed in 438 Italian subjects suggested a positive relation between the IVS7 repeat number and FVII levels. The lowest values were associated with the IVS7 + 7G allele. The screening of 52 patients with mild FVII deficiency showed an 8-fold increase in frequency (8%) of this allele, and among heterozygotes for identical mutations, lower FVII levels were observed in the IVS7 + 7G carriers. This frequent genetic component participates in the phenotypic heterogeneity of FVII deficiency. The evaluation of the individual contribution of polymorphisms was assisted by the expression of each IVS7 variant, as a minigene, in eukaryotic cells. The novel quantitative analysis revealed that higher numbers of repeats were associated with higher mRNA expression levels and that the IVS7 + 7G allele, previously defined as a functionally silent polymorphism, was responsible for the lowest relative mRNA expression. Taken together, these findings indicate that the IVS7 polymorphisms contribute to the plasmatic variance of FVII levels via differential efficiency of mRNA splicing. These studies provide further elements to understand the control of FVII levels, which could be of importance to ensure the hemostatic balance under pathologic conditions.
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PMID:Modulation of factor VII levels by intron 7 polymorphisms: population and in vitro studies. 1082 24

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. In addition, abnormalities of coagulation and fibrinolysis have been reported in patients with uremia. However, whether these hemostatic abnormalities lead to cardiovascular disease in dialysis patients is currently unknown. Therefore, we investigated the association of hemostatic factors with ischemic heart disease (IHD) in patients on peritoneal dialysis and hemodialysis. The study patients comprised 30 continuous ambulatory peritoneal dialysis patients and 18 hemodialysis patients. Twenty healthy subjects served as controls. We evaluated each subject's hemostatic factors, including factor VII, factor XII, thrombin-antithrombin III complex (TAT), fibrinogen, plasmin-antiplasmin complex (PIC), plasminogen activator inhibitor (PAI-1), and D-dimer. In dialysis patients, IHD was diagnosed by documented myocardial infarction or positive result on coronary angiogram or by positive thallium myocardial scintigraphy. Factor VII, fibrinogen, PIC, and D-dimer levels were significantly higher in the two dialysis groups than in controls. All hemostatic variables were similar between the two dialysis groups. Subject age (p = 0.005), PIC (p = 0.005), and D-dimer level (p = 0.003) were significantly higher in patients with IHD than in patients without IHD in the dialysis groups. Multiple logistic regression analysis showed that only patient age and D-dimer levels were independent predictors of IHD. Adjusted odds ratio for IHD was 1.06 for each 10 ng/mL increase of D-dimer (p = 0.06). In CAPD patients, only D-dimer was independently associated with IHD (odds ratio: 1.06, p = 0.03). We conclude that multiple hemostatic abnormalities are present in dialysis patients and that elevated D-dimer levels are independently associated with prevalent IHD.
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PMID:Coagulation and fibrinolysis factors in dialysis patients with and without ischemic heart disease. 1104 82

The coagulation, fibrinolytic, and platelet activating systems are complex and interact extensively, and with other systems such as inflammation. Key reactions often require biomembranes, suggesting that dietary lipids, to the extent that they influence membrane composition, may have important regulatory roles. Also, recent evidence suggests that both postprandial and fasting lipoproteins may be associated with either factor levels or activation state or both. This issue has added importance because several hemostatic and fibrinolytic factors are known CVD risk factors. Although there are associations between fasting lipid levels and several coagulation and fibrinolytic factors, the mechanisms are unclear, as are the implications for intervention. In general, postprandial lipids are at least somewhat procoagulant because they activate factor VII. It remains to be demonstrated, however, that this postprandial activation has important clinical correlates. Dietary supplementation with marine omega-3 fatty acids does prolong the bleeding time and may decrease thrombotic potential; however, other than this, little is known about the direct effects of dietary fatty acids on hemostatic and fibrinolytic activities. Much work is needed in carefully controlled studies to expand our knowledge in this important area.
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PMID:Diet and hemostatic factors. 1112 17

-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all P:<0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen. The potential for beneficial cardiovascular effects of tamoxifen in healthy women is suggested.
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PMID:Tamoxifen and cardiac risk factors in healthy women: Suggestion of an anti-inflammatory effect. 1115 62

Increased coagulation factors found in dialysis patients may explain in part the high prevalence of thrombotic cardiovascular disease. Several studies showed low-dose warfarin is effective in decreasing coagulation factors and preventing thrombosis without increasing the risk of bleeding. To evaluate the effects of fixed low-dose warfarin therapy on thrombogenesis in continuous ambulatory peritoneal dialysis (CAPD) patients, 76 CAPD patients were assigned randomly to treatment and disease control groups. The treatment group received 2 mg of warfarin daily for 12 months. International normalized ratio (INR) of the prothrombin time and plasma levels of factor VII, D-dimer, von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) were measured before and 3, 6, and 12 months after the start of medication. The same parameters were measured in 30 healthy volunteers at the beginning of the study and in the disease control group during the study period. Of 76 patients, 60 completed the study. Deaths from atherosclerotic cardiovascular disease (cerebral infarction or acute myocardial infarction) occurred in 1 patient in the treatment group (n = 29) and 3 in the disease control group (n = 31), which was not statistically significant. No major bleeding occurred during the study period. With administration of warfarin, there was a small increase in INR in the treatment group. CAPD patients at baseline had significantly higher plasma factor VII, D-dimer, vWF, and PAI-1 levels than normal controls. Warfarin therapy lowered plasma factor VII and D-dimer levels. No change was seen in vWF and PAI-1 levels. In the disease control group, these hemostatic factors showed no change during the study period. There was a negative correlation between serum albumin and INR in the treatment group during the study period. Fixed low-dose warfarin was effective in partially reversing the thrombogenic coagulation profile in CAPD patients without a big increase in the risk of bleeding.
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PMID:Effects of fixed low-dose warfarin on hemostatic factors in continuous ambulatory peritoneal dialysis patients. 1115 76

Currently, the established risk factors for cardiovascular disease (CVD) are largely environmental in nature. Conflicting studies have suggested that mutations in specific coagulation genes may also provide a genetic basis for CVD risk. We reviewed clinical studies that examined the role of single nucleotide polymorphisms in coagulation and platelet factors, and a biochemical factor to determine if specific genotypes are correlated with patients with a history of arterial thrombotic diseases (acute coronary syndromes or stroke). A meta-analysis was performed on studies for factors II (G20210A variant), V Leiden (G1691A), VII (R353Q), glycoprotein (GP) IIIa receptor (PI(A1/A2)), and methylenetetrahydrofolate reductase (MTHFR, C677T). There was no correlation for factor II or factor V polymorphisms to coronary artery disease (CAD) in 5,607 and 5,431 patients studied, respectively. There was also no correlation for factor II variants and stroke in 3,451 patients studied. For factor V, statistical significance was achieved for the G1691A variant on 3,399 patients with stroke (odds ratio [OR] 1.43, 95% confidence intervals [CI] 1.03 to 1.97). The GP IIIa PI(A1/A2) genotype was associated with increased risk for CAD in 7,920 patients (OR 1.12, 95% CI 1.01 to 1.24), but not for 1,855 patients who had a stroke (OR 0.80, 95% CI 0.62 to 1.04). The combined RQ and RR genotypes of factor VII R353Q were correlated to a reduced risk for CVD in 2,574 patients (OR 0.78, 95% CI 0.65 to 0.93), whereas the QQ genotype had offered more protection (OR 0.53, 95% CI 0.27 to 1.03). The TT homozygous variant of MTHFR was associated with CAD risk in 5,644 patients studied (OR 1.30, 95% CI 1.11 to 1.52) but not for 3,075 patients with stroke. This study shows that for some genes, further studies are unnecessary, whereas for others, no more enrollments are needed. The impact of certain genotypes must be examined in relation to other established risk factors and potentially new therapeutic strategies.
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PMID:Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. 1139 54

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