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)

Oxidative stress and defective fatty acid metabolism in diabetes may lead to impaired nerve perfusion and contribute to the development of peripheral neuropathy. We studied the effects of 2-week treatments with evening primrose oil (EPO; n = 16) or the antioxidant alpha-lipoic acid (ALA; n = 16) on endoneurial blood flow, nerve conduction parameters, lipids, coagulation, and endothelial factors, in rats with streptozotocin-induced diabetes. Compared with their nondiabetic littermates, untreated diabetic rats had impaired sciatic motor and saphenous sensory nerve-conduction velocity (NCV; P <.001), reduced endoneurial blood flow (P <.001), and increased serum triglycerides (P <.01), cholesterol (P < 0.01), plasma factor VII (P <.0001), and von Willebrand factor (vWF; P <.0001). Plasma fibrinogen and serum high-density lipoprotein concentrations were not significantly different. Treatment with either ALA or EPO effectively corrected the deficits in NCV and endoneurial blood flow. ALA was associated with marked and statistically significant decreases in fibrinogen, factor VII, vWF, and triglycerides (P <.01, paired t tests before v after treatment). In contrast, EPO was associated with significant (P <.05) increases in fibrinogen, factor VII, vWF, triglycerides, and cholesterol and a significant decrease in high-density lipoprotein. Changes in levels of coagulation factors and lipids, qualitatively similar to those found with EPO, were obtained with a diet containing sunflower oil (to control for calorific and lipid content) or with a normal diet alone. Blood glucose and hematocrit levels were not significantly altered by treatments. These data suggest that although both ALA and EPO improve blood flow and nerve function, their actions on vascular factors differ. The marked effects of ALA in lowering lipid and hemostatic risk factors for cardiovascular disease indicate potential antithrombotic and antiatherosclerotic actions that could be of benefit in human diabetes and merit further study.
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PMID:The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. 1147 72

In order to determine the role of two polymorphisms in the factor VII gene (R353Q and intron 7 hypervariable region) in the susceptibility to develop early myocardial infarction, a total of 175 patients with acute myocardial infarction aged 50 years or less (mean age 41+/-7 years) and 200 controls (average age 42+/-6) without cardiovascular disease were genotyped for these polymorphisms. Gene and genotype frequencies did not differ between patients and controls. Although the 353-QQ genotype was at a higher frequency among controls (4%) compared to patients (1%), the difference did not reach statistical significance. Carriers of the H7-allele (intron 7 polymorphism) were at a slightly higher frequency among patients (51 vs. 43%; P=0.19; OR=1.36; 95% CI=1.09-1.70). Our data suggest a lack of association between both polymorphisms in the factor VII gene and early myocardial infarction in our population.
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PMID:Lack of association between polymorphisms of the coagulation factor VII and myocardial infarction in middle-aged Spanish men. 1157 16

Hypertriglyceridemia (HTG) is an independent risk factor for cardiovascular disease (CVD). Hemostatic variables [factor VII antigen (FVIIag), factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), free and endothelial-associated (EC) tissue factor pathway inhibitor (TFPI) antigen, pre- and post-heparin total TFPI activity, EC-TFPI activity, prothrombin fragment 1 + 2 (F1 + 2), fibrinogen and D-dimer] were compared between 18 HTG patients and 20 controls to investigate whether HTG is associated with alterations in the extrinsic pathway and whether such alterations create a procoagulant state, as expressed by F1 + 2 and D-dimer levels. In addition, the effects of bezafibrate therapy (6 weeks, 400 mg/day) on these variables were studied in 18 HTG patients in a double-blind, placebo-controlled, cross-over study. FVIIag, FVIIc, free TFPI and fibrinogen were significantly higher in HTG patients (by 44, 30, 45 and 31%, respectively; all P < 0.02), while FVIIa, EC-TFPIag and activity, total TFPI activities, F1 + 2 and D-dimer levels were similar in patients and controls. Bezafibrate reduced serum TG and fibrinogen levels (by 62 and 20%, respectively; both P < 0.001), whereas the other hemostatic variables were unaffected. In conclusion, the observed alterations in the extrinsic pathway in HTG are not associated with a procoagulant state. In contrast, the presence of elevated fibrinogen levels in HTG might enhance the risk for CVD. Bezafibrate therapy improved the adverse lipid profile and decreased fibrinogen levels in HTG patients.
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PMID:Alterations in the extrinsic pathway in hypertriglyceridemia do not cause a 'procoagulant state': effects of bezafibrate therapy. 1173 72

Previous research concerning protective cardiovascular properties of olive oil has focussed on the beneficial consequences on blood cholesterol levels of substituting dietary saturated fatty acids with oleic acid. Despite evidence implicating raised circulating triglycerides in the postprandial state in the pathogenesis of atherosclerosis and thrombosis, little research had been conducted to investigate effects of monounsaturated fatty acids on postprandial events. In a case control study of southern (n = 30) versus northern European (n = 30) men, significant differences in postprandial triglyceride and apolipoprotein (apo) B-48 response were observed, with evidence of attenuated and potentially beneficial responses in the Southern Europeans. In a randomised controlled study manufactured foods typical of the Northern European food culture, were used to deliver diets rich in either saturated or monounsaturated fatty acids (from olive oil). During the period of the olive oil enriched diet, LDL-cholesterol levels were 15% lower (p < 0.001) than during the saturated fat diet. Postprandial triglyceride response was shifted towards the profile seen in southern European men and the postprandial activation of factor VII, as well as the production of factor VII antigen, was reduced on the olive oil diet. The study demonstrated significant improvements in biomarkers for cardiovascular disease in subjects osed to high olive oil diets (Southern Europeans) or transferred to such diets in the short term (Northern European volunteers). The study produced novel findings with respect to potential mechanisms by which diets high in monounsaturated fatty acids (MUFA) can reduce population risk of cardiovascular disease.
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PMID:Beneficial nutritional properties of olive oil: implications for postprandial lipoproteins and factor VII. 1189 55

This study examined the possible relationship between Karasek's job strain model and blood coagulation factors VII and VIII as risk factors for cardiovascular disease in Korean male workers. Based on the postulation of the model, we invited 160 male workers (40 people each subgroup) using a stratified sampling from the base population (n = 1071). In univariate analyses, decision latitude was negatively related to blood coagulation factors VII and VIII. Work demand was positively related to coagulation factor VIII, but not to factor VII. Hierarchical multiple regression analyses showed that job strain was associated with blood coagulation factor VIII after controlling for smoking, blood pressure, total cholesterol, and HDL cholesterol. These results indicate that job characteristics may be related to blood coagulation, and contribute to the development of cardiovascular disease with other classical risk factors.
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PMID:Job characteristics and blood coagulation factors in Korean male workers. 1244 51

Serum components, such as lipoproteins, coagulation factors (factor VII, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), fibrinogen), and homocysteine have been associated with cardiovascular disease. Dietary intervention with a low-fat, low-cholesterol diet has favorably influenced cardiovascular disease and certain food, specifically the consumption of nuts, has been associated with reduced cardiovascular risks. The effects of walnuts, as part of a low-fat, low-cholesterol diet, on serum cardiovascular risk factors were determined. Sixty-seven (67) outpatients with borderline high total cholesterol following a low-fat, low-cholesterol diet for six weeks before being randomly assigned to continue the diet or have 64 grams/day of walnuts in conjunction with the diet. After six weeks, the patients' diets were switched. Therefore, all patients consumed 64 grams/day of walnuts for six weeks during part of the trial as part of a low-fat, low cholesterol diet. Serum lipids demonstrated a significant reduction in triacyglycerols and favorable trend with decreases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and a slight increase in high-density lipoprotein (HDL) cholesterol. No statistical effects on homocysteine or the coagulation factors were observed. However, there was a slight favorable trend for tPA and PAI-1. This study demonstrated that walnuts, when consumed as part of a low fat, low-cholesterol diet, have a beneficial effect on serum cardiovascular risk factors. However, these changes may not explain all of the beneficial effects that walnut consumption has on cardiovascular disease.
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PMID:Effects of walnut consumption as part of a low-fat, low-cholesterol diet on serum cardiovascular risk factors. 1246 11

Elevated plasma levels of factor VII and fibrinogen are risk factors for cardiovascular disease, especially arterial thrombosis. Oral contraceptive use increases factor VII and fibrinogen plasma levels. It has been described that DNA polymorphisms are associated with the plasma levels of hemostatic variables and their regulation. The R/Q353 polymorphism in the factor VII gene and the -455G/A polymorphism in the fibrinogen beta-gene are associated with plasma levels of factor VII and fibrinogen, respectively. We analysed data of a randomised study (n = 95) in which two types of oral contraceptives were compared with regard to their effect on factor VII and fibrinogen, in which we also determined R/Q353 and -455G/A polymorphisms. Women were allocated randomly to either receiving a monophasic oral contraceptive containing 75 micrograms of gestodene and 20 micrograms of ethinyl estradiol, or 150 micrograms of desogestrel and 20 micrograms of ethinyl estradiol. Blood was taken before treatment and after 3 and 6 months of oral contraceptive use. Factor VII and fibrinogen increased significantly after 3 and 6 months of oral contraceptive use; the increase in factor VII was higher in the desogestrel group than in the gestodene group at 3 and 6 months. For fibrinogen, there were no intergroup differences at 3 and 6 months. At baseline, an association between genotype and plasma factor VII and fibrinogen levels was observed. In multivariate analysis, the R/Q353 polymorphism and the type of oral contraceptive were determinants of the effect on the change in factor VII, with the highest increase in women carrying the Q allele and using the desogestrel-containing oral contraceptive, and the lowest increase in women with the RR genotype who use the gestodene-containing oral contraceptive. For fibrinogen, no interaction among type of oral contraceptive, -455G/A polymorphism, and change in plasma levels was observed. We conclude that an individual's genetic variation may contribute to the response of plasma factor VII to oral contraceptive use.
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PMID:Genetic polymorphisms modify the response of factor VII to oral contraceptive use: an example of gene-environment interaction. 1261 80

Dietary trans fatty acids are associated with increased risk of CHD. We hypothesized that the changes in plasma lipids associated with a high intake of trans fatty acids would cause adverse effects on procoagulant and fibrinolytic activities. A randomized crossover controlled feeding study was conducted in twenty-nine men. A trans-rich diet supplying 10 % energy as trans- 18:1 was compared with diets in which the trans fatty acids were replaced either with carbohydrate or oleate; each diet was taken for 2 weeks in random order. Fasting fibrinogen and d-dimer concentrations and factor VII coagulant, plasminogen activator inhibitor type 1 and tissue plasminogen activator did not differ between diets. Postprandially, tissue plasminogen activator activity increased and plasminogen activator inhibitor type 1 activity decreased on all diets. Factor VIIc increased postprandially by 15 and 17 % on the trans and oleate diets respectively, compared with an 11 % increase on the carbohydrate diet; the mean difference between oleate and carbohydrate diets was 6 (95 % CI 0.2, 11.9) %. The LDL-cholesterol:HDL-cholesterol and apolipoprotein B : apolipoprotein A-I ratios increased by 13 (95 % CI 5.7, 21.8) and 10 (95 % CI 3.1, 17.2) % respectively on the trans diet compared with the oleate diet and by 6 (95 % CI 0.1,12.7) and 7 (95 % CI 0, 13.5) % respectively compared with the carbohydrate diet. Plasma HDL2-cholesterol concentration was 18 (95 % CI 0.7, 35.9) % lower on the trans diet compared with the oleate diet. The results confirm adverse effects of trans fatty acids on HDL-cholesterol concentrations, but suggest that trans fatty acids do not have any specific effects on known haemostatic risk markers for cardiovascular disease in healthy young men in the short-term.
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PMID:High intakes of trans monounsaturated fatty acids taken for 2 weeks do not influence procoagulant and fibrinolytic risk markers for CHD in young healthy men. 1282 93

Inflammation and thrombosis are important mechanisms in cardiovascular disease, as illustrated by the consistent association between inflammatory and hemostatic variables and the risk of cardiovascular events in epidemiological studies. However, the relationship between plasma concentrations of inflammatory and hemostatic markers and the severity of atherosclerosis is not yet well studied. We have evaluated 325 men and 370 women of 60 years, participating in the Danish Glostrup study. We diagnosed atherosclerosis by ultrasonographic measurement of intima-media thickness (IMT) of the right carotid artery and the assessment of plaque occurrence. Plasma samples were analyzed for the concentration of C-reactive protein (CRP), fibrinogen, d-dimer, plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue-type plasminogen activator (t-PA) antigen and activity, factor VII (FVII) antigen, FVII coagulant activity (FVII:C) and activated FVII (FVIIa). DNA variations were determined for fibrinogen, PAI-1, t-PA, FVII, factor XIII and methylene tetrahydrofolate reductase (MTHFR). Subjects with high IMT (upper 10% of distribution, n = 63) had higher CRP levels [2.2 mg L-1 (SE 0.3)] than subjects with IMT in the lowest tertile (n = 217) [1.7 mg L-1 (SE 0.1), P = 0.04], whereas there was no association between the hemostatic variables and IMT. There was an association between fibrinogen and d-dimer concentrations and number of plaques (P < 0.01), whereas there were no associations between CRP and the other hemostatic variables and the number of plaques. Genetic variation in the t-PA and MTHFR gene was associated with IMT. In conclusion, in the Glostrup population study, thrombosis and inflammation are associated with the severity of atherosclerosis, as reflected by IMT and plaque occurrence.
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PMID:Inflammation, thrombosis and atherosclerosis: results of the Glostrup study. 1287 60

Recent large clinical trials have demonstrated that HMG-CoA reductase inhibitors, or statins, markedly reduce morbidity and mortality when used in the primary and secondary prevention of cardiovascular disease. It has been established that the benefits of statin therapy in cardiovascular disease can be explained not only by the lipid-lowering potential of statins but also by nonlipid-related mechanisms (so-called "pleiotropic effects") that contribute to the positive effect of statins on the incidence of cardiovascular events. The coagulation and fibrinolytic systems are two separate but reciprocally linked enzyme cascades that regulate the formation and breakdown of fibrin. Numerous studies have demonstrated that disturbances of coagulation and fibrinolysis contribute to the development and progression of atherosclerosis, and that they affect the incidence of atherosclerosis-related clinical events. High plasma levels or activities of fibrinogen, factor VII, factor VIII, von Willebrand factor (vWF), soluble thrombomodulin, tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) are thought to be associated with increased morbidity and mortality related to cardiovascular disease. Experimental studies and many clinical studies have recently shown that statins produce favourable effects on haemostatic parameters, including those that are risk factors for cardiovascular disease. Statins diminish procoagulant activity, which is observed at different stages of the coagulation cascade, including tissue factor (TF) activity, conversion of prothrombin to thrombin and thrombin activity. In some studies, statins also reduced fibrinogen levels. By altering the levels and activities of tPA and PAI-1, statins seem to stimulate fibrinolysis. The data on the effects of combined treatment with statins and other drugs on haemostasis are rather limited. They suggest that statins combined with fibric acid derivatives, omega-3 fatty acids and 17beta-estradiol are superior to statins alone. The only two clinical studies performed in patients with acute coronary syndromes showed a relatively weak effect of statins on haemostasis in those patients. Although various statins may produce different effects on individual variables, there are no convincing data showing that differences in their physicochemical and pharmacokinetic properties significantly alter their net effect on excessive procoagulant activity. Apart from the lipid-lowering effect, statins suppress the synthesis of several important nonsterol isoprenoids derived from the mevalonate pathway, especially farnesyl and geranylgeranyl pyrophosphates, which via enhanced protein prenylation, are involved in the regulation of many cellular processes. It is presumed that the inhibitory effect of statins on the mevalonate pathway is involved in the regulation of some key steps of coagulation and fibrinolysis processes. In this way they probably regulate the synthesis of TF, tPA and PAI-1, and perhaps they also control the generation and activity of thrombin. The beneficial effects of statins on coagulation and fibrinolysis may be responsible for their ability to decrease the number of cardiovascular events. The lipid-independent effects of statins on haemostasis may contribute to the marked decrease in the incidence rates of mortality, hospitalisation and revascularisation in patients treated with these drugs.
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PMID:Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. 1292 88


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