Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VII. The association of serum-triglycerides with factor VII may differ between the genotypes, but the results of earlier studies were inconsistent and did not include older people. We studied FVII, triglycerides and the R/Q353 polymorphism in the Rotterdam Study. In 1158 older subjects (489 men and 669 women) FVII:C, factor VII:Chr, serum-triglycerides and the R/Q353-genotype were determined. In women triglycerides were positively associated with FVII:Chr and FVII:C (FVII:Chr: beta = 12.4% PP/mmol/L, CI: 10.3-14.5; FVII:C: beta = 13.1% PP/mmol/L, CI: 10.4-15.8). These associations varied by genotype (FVII:Chr: RR: beta = 11.7, CI: 9.6-13.8, RQ/QQ: beta = 7.9, CI: 4.6-11.2; FVII:C: RR: beta = 12.5, CI: 9.5-15.5, RQ/QQ: beta = 6.4, CI: 1.4-11.4). In men, the associations of FVII:Chr and FVII:C with triglycerides were weaker (FVII:Chr: beta = 5.9, CI: 4.1-7.7; FVII:C: beta = 8.7, CI: 6.2-11.2). There was no difference between the genotype groups. These results suggest that only in older women the strength of the association of factor VII with serum-triglycerides varies according to genotype of the R/Q353 polymorphism.
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PMID:Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: differences between older men and women. 930 39

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

Circulating concentrations of plasminogen activator inhibitor-1 (PAI-1), factor VII and fibrinogen have all been related to vascular risk in large prospective studies. Evidence indicates that all three proteins are increased in the presence of insulin resistance and factor VII and PAI-1 correlate strongly with circulating levels of insulin and lipids. Polymorphisms of the genes coding for PAI-1, factor VII and fibrinogen have been investigated in relation to gene environment interactions and vascular risk. Three polymorphisms have been described in the PAI-1 gene, a 3' Hind III RFLP, an intronic CA repeat and a 4G/5G insertion deletion 675 bp 5' of the start site of transcription. The 4G/5G site has been shown to be triglyceride responsive and higher levels of PAI-1 have been reported in subjects homozygous for the 4G allele. Three out of four case control studies have related possession of the 4G/4G genotype to an increased risk of coronary artery disease and our studies in patients undergoing coronary angiography indicate that this is due to increased myocardial infarction rather than atheroma. We have investigated 600 subjects with cerebrovascular disease and found no relationship to the 4G/5G polymorphism. Two major polymorphisms have been identified in the factor VII gene, a promoter decanucleotide repeat and a G-A substitution at codon 353. Evidence indicates that the latter mutation affects factor VII levels by interfering with intracellular processing of the molecule and subjects homozygous for the adenine genotype (M2/M2) have levels of factor VII 20-30% lower than M1/M2 or M1/M1 carriers. Two studies have, however, failed to show a relationship between genotype and cardiovascular disease and we have found no association with cerebrovascular disease. A number of mutations have been described in the genes coding for the alpha, beta and gamma chains of fibrinogen. These polymorphisms are reported to be responsible for from 3% to 50% of circulating levels in various studies and there is evidence that the effect of smoking is genotype specific. In the ECTIM study the beta Bcl I polymorphism has been related to cardiovascular disease and work from our unit has related the Bbeta448 polymorphism to the presence of cerebrovascular disease in women. Further prospective studies are warranted to evaluate the role of these genes in disease.
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PMID:Polymorphisms of coagulation/fibrinolysis genes: gene environment interactions and vascular risk. 943 Mar 99

Intake of dietary flavonols and flavones was inversely associated with risk for cardiovascular disease in several epidemiologic studies. This may have been due to effects on hemostasis because flavonoids have been reported to inhibit platelet aggregation in vitro. We indeed found that 2500 micromol/L of the flavonol quercetin and the flavone apigenin significantly inhibited collagen- and ADP-induced aggregation in platelet-rich plasma and washed platelets by approximately 80-97%. However, lower concentrations, such as might occur in vivo, had no effect. To test this in vivo we fed 18 healthy volunteers 220 g onions/d providing 114 mg quercetin/d, 5 g dried parsley/d providing 84 mg apigenin/d, or a placebo for 7 d each in a randomized crossover experiment with each treatment period lasting 2 wk. Onion consumption raised mean plasma quercetin concentrations to 1.5 micromol/L; plasma apigenin could not be measured. No significant effects of onions or parsley were found on platelet aggregation, thromboxane B2 production, factor VII, or other hemostatic variables. We conclude that the antiaggregatory effects of flavonoids seen in vitro are due to concentrations that cannot be attained in vivo. Effects of dietary flavonols and flavones on cardiovascular risk are possibly not mediated by hemostatic variables.
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PMID:Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. 945 73

Elevated plasma factor VII (FVII) levels are reported to be associated with cardiovascular disease in both Caucasians and Japanese. Recent reports indicate that individuals with the FVII 353Q allele have decreased plasma FVII levels. Thus, we investigated the association between lacunar stroke and the FVII R353Q polymorphism in 137 hypertensive patients with silent or overt lacunar stroke (stroke group), 83 non-stroke hypertensives without any lacunae detected by magnetic resonance imaging (non-stroke group), and 97 normotensive control subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive control group). The frequency of the FVII 353Q allele was 0.057 in the normotensive control group, 0.051 in the non-stroke group and 0.061 in the stroke group. These frequencies, as well as genotype distribution, were not significantly different from each other, even when we subclassified the ischemic group into silent (n = 54) and clinically overt (n = 64) lacunar stroke subgroups. These results suggest that the FVII 353Q allele is not an important genetic determinant for cerebrovascular disease in Japanese individuals.
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PMID:Factor VII R353Q polymorphism and lacunar stroke in Japanese hypertensive patients and normotensive controls. 949 Dec 71

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Cardiovascular disease remains a major cause of mortality among postmenopausal women. After menopause, atherogenesis is promoted by a number of metabolic and vascular changes. A multitude of observational clinical studies have come to the conclusion that estrogen replacement therapy (ERT) reduces cardiovascular risk by approximately 50% and that estrogen's favorable effects on the lipid profile can explain only 25-50% of the overall observed reduction. Estrogens are now known to have potent anti-atherogenic properties through lipid and non-lipid mechanisms; both will be highlighted in view of the recent literature. Estrogens induce favorable changes on lipids and lipoproteins, partly by increasing HDL-cholesterol and decreasing both LDL-cholesterol and lipoprotein (a). Non-lipid mechanisms of estrogen action include decreasing insulin resistance, serum fibrinogen, factor VII and plasminogen activator inhibitor-1 (PAI-1). Moreover, estrogens maintain endothelial cell integrity, decrease expression of adhesion molecules, lower systemic blood pressure, promote vasodilatation, decrease platelet aggregability, inhibit vascular smooth muscle cell proliferation, possess potent antioxidant and calcium antagonist activities, inhibit adrenergic responses and downregulate platelet and monocyte reactivity. Also mentioned are recent reports linking estrogen to the renin-angiotensin system, relaxin, serotonin and homocysteine. What was once thought of as a simple action is now being increasingly appreciated as a complex, multifaceted mechanism, which serves to prove that estrogen is a powerful cardiovascular agent.
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PMID:Estrogen replacement therapy and cardiovascular protection: lipid mechanisms are the tip of an iceberg. 952 10

The effects of chronic cigarette smoking on the coagulation system were examined in 2964 men aged 50 to 61 years and clinically free of cardiovascular disease. Factor VII activity (VIIc), factor VII antigen (VIIag), prothrombin fragment 1+2 (F1.2), fibrinopeptide A (FPA) and fibrinogen were measured in all participants, and activated factor VII (VIIa), factor IX activation peptide (IX pep) and factor X activation peptide (X pep) in a large sub-sample. The levels of all indices except FPA differed significantly between non-smokers, ex-smokers and current smokers. After adjustment for other conventional cardiovascular risk factors, mean VIIc was raised slightly by 3% in ex-smokers and current smokers as compared with non-smokers, owing to increases in VIIa and VIIag. Plasma IX pep, X pep, F1.2 and fibrinogen concentration were highest in current smokers, intermediate in ex-smokers and lowest in non-smokers. These findings accord with the increased risk of arterial thrombosis in smokers.
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PMID:Activation of the coagulant pathway in cigarette smokers. 953 Oct 38

The relationships of central obesity and physical fitness to indexes of hemostatic, lipid and glucose metabolism both at baseline and after 1 year of diet and exercise intervention were examined in 209 sedentary middle-aged men and women with increased coronary risk factor levels. Central obesity was measured as either waist circumference or waist/hip ratio. Maximal oxygen uptake was used as a measure of physical fitness. The cross-sectional results show that there were significant correlations between waist circumference and euglobuline clot lysis time (r = 0.23), factor VII (r = 0.16), glucose and insulin before and after 1 h glucose load (r ranging from 0.32 to 0.50). The 1-year intervention gave the following associations between changes in waist circumference and changes in: euglobuline clot lysis time (r = 0.27), factor VII (r = 0.19), carbohydrate variables and lipids (magnitude of r ranging from 0.19 to 0.43). Also the other indexes of obesity and physical fitness showed significant correlations to indexes of hemostatic, lipid and glucose variables, both cross-sectionally and for changes after the 1-year intervention. The associations between changes in central obesity and changes in indexes of hemostatic, carbohydrate and lipids were generally stronger during 1 year of diet and exercise intervention than those found at baseline. Multiple regression analyses with waist circumference, waist/hip ratio, percent body fat and Vo2 max as independent variables and indexes of hemostatic, carbohydrate and lipid metabolism as dependent variables showed that waist circumference was a significant predictor for indexes of the hemostatic, carbohydrate and lipid metabolism, mostly independent of physical fitness. The cross-sectional and 1-year change results support each other and therefore underscore the importance of abdominal obesity as an important risk factor for cardiovascular disease.
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PMID:Associations between central obesity and indexes of hemostatic, carbohydrate and lipid metabolism. Results of a 1-year intervention from the Oslo Diet and Exercise Study. 956 16


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