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)

Type 2 diabetes is characterised by insulin resistance in association with clustering of atherothrombotic risk factors (dysglycaemia, hyperinsulinaemia, hypertension, raised triglyceride, low HDL cholesterol and increased levels of plasminogen activator inhibitor-1 (PAI-1) and clotting factor VII). There is a 3-5 fold increase in risk of myocardial infarction rising to 10-20 fold in the presence of microalbuminuria and overall around 70-75% of subjects with type 2 diabetes die of cardiovascular disease. However, classical risk factors which associate with insulin resistance do not account for all the increased burden of vascular disease in diabetic subjects. Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow. Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein. In addition recent studies indicate that metformin has direct effects on fibrin structure/function and stabilises platelets, two important components of arterial thrombus. The United Kingdom Prospective Diabetes Study (UKPDS) reported that metformin was associated with a 32% reduction in any diabetes related endpoint (p<0.002), a 39% reduction in myocardial infarction (p<0.01) and a non-significant 29% fall in microvascular complications. The figures for macrovascular complications compare favourably for those described for other cardioprotective agents such as ACE inhibitors and statins. These findings confirm metformin as first line therapy in the management of obese insulin resistant type 2 diabetes and in the prevention of the vascular complications of this common condition.
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PMID:Beneficial effects of metformin on haemostasis and vascular function in man. 1450

Impaired clearance of chylomicron remnants is associated with increased risk of atherosclerosis and cardiovascular disease. An intake of 40 to 50 g of fat in a meal results in significant lipemia in healthy adults, with consecutive fat-containing meals enhancing the lipemia. This would suggest that limiting fat intake to approximately 30 g on each eating occasion would minimize postprandial lipemia. Sedentary behavior and obesity independently impair the postprandial metabolism of lipids. Postprandial lipemia causes endothelial dysfunction and results in a transient increase in factor VII activated (FVIIa) concentration. Plasminogen activator inhibitor type-1 activity is associated with fasting plasma triacylglycerol concentration, but is not influenced by postprandial lipemia. Trans-18:1 acid appears to increase cholesterol ester transfer activity acutely compared with oleate. Randomized stearic acid-rich fats result in less postprandial lipemia and a lower postprandial increase in FVIIa, whereas unrandomized cocoa butter results in similar postprandial lipemia and increases in FVIIa compared with oleate. A background diet containing in excess of 3 g/d of long-chain omega-3 fatty acids decreases postprandial lipemia by stimulating lipoprotein lipase expression and decreasing very low-density lipoprotein synthesis, but a diet enriched in alpha-linolenic acid (up to 9.5 g/d) does not show these effects. Future research on diet and postprandial lipids needs to exploit newly gained knowledge on the regulation of adipocyte metabolism by adipokines and nuclear hormone receptors, particularly with regard to fat patterning and reverse cholesterol transport.
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PMID:Dietary fat and postprandial lipids. 1452 77

Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index > or = 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-beta 1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-beta 1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-beta 1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-beta 1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-beta 1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-beta 1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.
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PMID:Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women. 1460 68

Candidate gene polymorphisms related to inflammation, thrombosis and lipid metabolism have been implicated in the development of ischemic stroke. Using DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we genotyped 92 polymorphisms from 56 candidate genes among 319 individuals who subsequently developed ischemic stroke and among 2092 individuals who remained free of reported cardiovascular disease over a mean follow-up period of 13.2 years to prospectively determine whether candidate gene polymorphisms contribute to stroke risk. After adjustment for multiple comparisons and age, smoking, body mass index, hypertension, hyperlipidemia and diabetes, two related to inflammation [a val640leu polymorphism in the P-selectin gene (OR=1.63, 95% CI 1.22-2.17, P=0.001) and a C582T polymorphism in the interleukin-4 gene (OR=1.40, 95% CI 1.13-1.73, P=0.003)] were found to be independent predictors of thrombo-embolic stroke. In bootstrap replications, the inclusion of genetic information from these two polymorphisms improved prediction models for stroke based upon traditional risk factors alone (ROC 0.67 versus 0.64). Two polymorphisms related to thrombosis (an arg353gln polymorphism in the factor VII gene and a T11053G polymorphism in the plasminogen activator inhibitor type-1 gene) and one related to lipid metabolism [a C(-482)T polymorphism in the apolipoprotein CIII gene] achieved nominal significance, but were not found to be independent predictors after multiple comparison adjustment. Two inflammatory candidate gene polymorphisms were identified which were independently associated with incident stroke. These population-based data demonstrate the ability of prospective, epidemiological studies to test candidate gene associations for athero-thrombotic disease.
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PMID:Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. 1468 4

Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and by bone loss. We evaluated cross-sectionally the association between periodontal disease and C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (t-PA), LDL-C, von Willebrand factor, and soluble tumor necrosis factor receptors 1 and 2. The final sample consisted of 468 men (ages 47-80 yrs), participating in the Health Professional Follow-up Study, who provided blood and were free of CVD, diabetes, and cancer. In multivariate regression models controlling for age, cigarette smoking, alcohol intake, physical activity, and aspirin intake, self-reported periodontal disease was associated with significantly higher levels of CRP (30% higher among periodontal cases compared with non-cases), t-PA (11% higher), and LDL-C (11% higher). Based on our data, periodontal disease showed significant associations with biomarkers of endothelial dysfunction and dyslipidemia, which may potentially mediate the association between periodontal and cardiovascular disease.
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PMID:Periodontal disease and biomarkers related to cardiovascular disease. 1474 54

The cause of many myocardial infarctions is occlusive thrombosis, or a blood clot that stops blood flow in a coronary artery. Hemostasis involves a complex system of factors, which normally form and degrade blood clots, that work within a delicate balance. Emerging evidence suggests that some hemostatic factors, including factor VII, fibrinogen, and plasminogen activator inhibitor-1, are associated with increased risk for cardiovascular disease (CVD). Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. Dietary supplementation with marine n-3 fatty acids prolongs bleeding time and may decrease risk for thrombosis. Factor VII coagulant activity modestly decreases with reductions in saturated fatty acid (SFA) intake and thereby may contribute to the beneficial effects of low SFA diets. Large triglyceride-rich particles formed during postprandial lipemia can support the assembly and function of coagulation complexes and seem to play a role in the activation of factor VII, and thus may partially explain increased CVD risk associated with increased postprandial triglyceridemia. As our understanding of the role of dietary fatty acids and hemostasis evolves, it is likely that we will be able to make specific dietary recommendations to further decrease CVD risk. At this juncture, however, increasing marine n-3 fatty acids and decreasing certain SFAs are leading strategies to reduce hemostatic CVD risk factors. An array of dietary strategies that target multiple CVD risk factors could have a greater impact on CVD than a single risk factor intervention strategy.
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PMID:Dietary fatty acids, hemostasis, and cardiovascular disease risk. 1499 64

In the Cardiovascular Health Study, the authors sought to evaluate the impact of chronic renal insufficiency (CRI) on cardiovascular risk status and outcomes in a representative sample of community-dwelling elderly adults. Defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men, CRI was present in 647 (11%) of 5808 participants. At baseline, the prevalence of clinical or subclinical cardiovascular disease was 64% in participants with CRI and 43% in those without CRI (odds ratio, 2.34; 95% confidence interval, 1.96-2.80). The incidence of cardiovascular disease events during follow-up was 3% per year in participants with creatinine levels <1.10 mg/dL and increased steadily to reach 7% per year in those with creatinine > or =1.70 mg/dL. Among the possible mediators for the association between CRI and cardiovascular morbidity are inflammatory (C-reactive protein, fibrinogen, and interleukin-6) and hemostatic (factor VII, factor VIII, plasmin-antiplasmin product, and D-dimer) biomarkers, all of which were significantly elevated in Cardiovascular Health Study participants with CRI. Future studies should evaluate the contribution of novel and traditional cardiovascular risk factors to the cardiovascular risk of elderly persons with CRI. The identification of CRI in the elderly and the use of cardiovascular prevention therapies represent a major opportunity to reduce their burden of cardiovascular morbidity.
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PMID:Chronic renal insufficiency and cardiovascular events in the elderly: findings from the Cardiovascular Health Study. 1501 Jun 54

Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p>0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.
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PMID:Association between obesity and a prothrombotic state: the Framingham Offspring Study. 1504 28

Abnormal tissue factor (TF) expression on vascular endothelial cells may account for thrombotic events associated with cardiovascular disease. The transcription factor nuclear factor-kappa B (NF-kappa B) activation plays a key role in endothelial cell injury and TF expression. Disruption of NF-kappa B activation in endothelial cells may inhibit TF expression and be protective in thrombosis. The purpose of the study was to determine whether NF-kappa B transcription factor decoy (TFD) could block TF expression. NF-kappa B TFD was transferred into cultured human umbilical cord vein endothelial cells (HUVEC) by liposomes, and the transfection efficiency was detected by flow cytometry. The effect of NF-kappa B TFD on TF mRNA levels was determined by reverse transcription-polymerase chain reaction. The expression of surface TF antigen was analyzed by flow cytometry. TF activity was studied by measuring enzymatic activation of factor X by the TF-activated factor VII complex. The results suggested that NF-kappa B decoy could be successfully transferred into HUVEC by liposome. The NF-kappa B TFD competed with the endogenous kappa B site sequence in the TF promoter for binding to transcription factor NF-kappa B in tumor necrosis factor-alpha-stimulated HUVEC, which could block the tumor necrosis factor-alpha-induced increase in TF mRNA levels, the upregulation of surface TF antigen and TF activity. This study demonstrated that NF-kappa B decoy could block HUVEC TF gene expression. Targeted genetic disruption of endothelial TF expression by NF-kappa B decoy may provide a possible therapeutic method for cardiovascular and thrombosis disease.
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PMID:An oligonucleotide decoy for nuclear factor-kappa B inhibits tumor necrosis factor-alpha-induced human umbilical cord vein endothelial cell tissue factor expression in vitro. 1531 Nov 57

We carried out a prospective cohort study to determine whether the plasma levels of fibrinogen, plasminogen, factor VII and lipoprotein (a) are predictors of ischemic stroke and all cardiovascular disease (CVD) events. The FINRISK '92 Hemostasis Study included a random sample of 2372 participants, who were followed-up from winter 1992 to 31 December 2001. During the follow-up, 75 ischemic stroke and 145 coronary events occurred. Of these, 169 were observed among participants free of known CVD at baseline. In this group, fibrinogen and plasminogen were positively associated with the risk of a CVD event with hazard ratios of 1.22 [95% confidence interval (CI), 1.05-1.41] and 1.22 (95% CI, 1.03-1.44), respectively, after adjusting for age, sex and conventional risk factors. Factor VII:C was associated with risk of a future CVD event only among persons with positive history of CVD at baseline (hazard ratio, 1.32; 95% CI, 1.00-1.73). Factor VII antigen was not associated with CVD risk. None of the measured hemostatic factors was a predictor of ischemic stroke events, with the possible exception of lipoprotein (a), which had a borderline significant association (hazard ratio, 1.25; 95% CI, 0.99-1.58). In conclusion, the present study supports the observations that fibrinogen and plasminogen are significant predictors of CVD events, independently of conventional risk factors.
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PMID:Hemostatic factors as predictors of stroke and cardiovascular diseases: the FINRISK '92 Hemostasis Study. 1574 99


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