Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data from the Whitehall II Study and others have demonstrated a role for the metabolic syndrome and fibrinogen underlying the association between social position and coronary heart disease. In this study, we examined the role of an additional hemostatic factor and marker of endothelial dysfunction, von Willebrand factor (vWF). Four thousand five hundred and forty-eight men and 1837 women were examined in the third phase of the study, which took place between 1991 and 1993. Employment grade was used as a measure of socioeconomic position. An inverse relation between employment grade and vWF was evident (P<0.0003). This employment grade gradient was apparent overall, and the relation persisted even when nonsmokers and participants with poor health were removed from the analyses (P=0.02). The difference between the highest (unified grades 1 to 6) and lowest (clerical/support) employment grades in vWF concentrations was 8.9 IU/dL (95% CI 6.0, 11.8; P<0.001) for men and 6.9 IU/dL (95% CI 4.0, 9.7; P=0.06) for women. vWF was associated with a number of biological factors that themselves showed an employment grade gradient, including fibrinogen (P<0.001), fasting and postload glucose (P<0.05) levels, and fasting and postload insulin (P<0.01) levels. Associations with smoking and alcohol intake were apparent. Smoking showed a threshold effect, such that only men who smoked >21 cigarettes per day produced a significantly increased vWF level (P<0.05) compared with lighter smokers. The health-related behaviors explained 25% of the grade gradient in men and 28% in women, while the biological factors accounted for 32% in men and 22% in women. We conclude that there is a grade gradient in vWF that was not fully explained by health-related behaviors and risk factors for coronary heart disease. These data are consistent with the hypothesis that endothelial dysfunction is part of the explanation for social inequalities in cardiovascular disease.
 ...
PMID:Social determinants of von willebrand factor: the Whitehall II study. 1089 27

Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well. We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions. This is a model for acute GHD without the alterations in body composition associated with GHD. We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting. In addition, we investigated the effect of pegvisomant under normal, i.e. fed, conditions. Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml, respectively). Fasting in combination with pegvisomant also decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml). Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting. Pegvisomant alone had no influence on insulin sensitivity. The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant. Among serum lipid concentrations, only serum triglycerides increased significantly as a result of pegvisomant alone (1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter). The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone. von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone (1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml). In conclusion, in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease. These data suggest that the secondary metabolic changes, e.g. abdominal obesity or inflammatory factors, that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD.
 ...
PMID:Acute effect of pegvisomant on cardiovascular risk markers in healthy men: implications for the pathogenesis of atherosclerosis in GH deficiency. 1170 72

Obese patients are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the haemostatic and fibrinolytic systems. Indeed, obese subjects tend to have higher values of fibrinogen, factor VII, factor VIII, von Willebrand factor and plasminogen activator inhibitor compared to non-obese subjects. Abdominal obesity, in particular, has been shown to be associated with disturbances in fibrinogen, factor VIII and von Willebrand factor, while less consistent results have been found for factor VII. Recently it has been demonstrated that the adipocyte itself is able to produce plasminogen activator inhibitor-1, possibly explaining the high levels found in obesity. Different studies have investigated the association between haemostatic and fibrinolytic parameters and the insulin resistance syndrome, often present in obese subjects. Fibrinogen has been found to be related to insulin, but it has been suggested that this relationship is not independent of the accompanying inflammatory reaction. Results from studies on the relationship between insulin resistance and factor VII, factor VIII and von Willebrand factor levels are inconsistent. In contrast, plasminogen activator inhibitor-1 has been found to correlate with all components of the insulin resistance syndrome, and can be considered as a true component of this metabolic syndrome. Weight loss seems to have a beneficial effect on factor VII--probably mediated through a reduction in triglycerides. Data on factor VIII and von Willebrand factor are scarce but weight loss does not seem to have an effect. Fibrinogen does not seem to be reduced by modest weight loss and a more substantial weight loss seems necessary to lower fibrinogen levels. In contrast, both modest and substantial weight loss have been found to significantly reduce plasminogen activator inhibitor-1 levels. In conclusion, the increased cardiovascular risk observed in obesity could in part be explained by the association between insulin resistance and components of the fibrinolytic and haemostatic systems. Whether this relationship is truly causal or indirect needs to be elucidated further.
 ...
PMID:Obesity, haemostasis and the fibrinolytic system. 1212 Apr 24

Elevated levels of haemostatic factors including tissue plasminogen activator (t-PA) antigen are associated with coronary heart disease in Europeans but data in South Asians are sparse. We performed a cross-sectional study of 111 healthy men and women aged 40-55 years (56 European and 55 Asian) frequency matched across a wide range of body mass index (17-34 kg/m2). All subjects had detailed adiposity and metabolic measurements, and five haemostatic factors were determined. South Asians had greater insulin resistance than Europeans (fasting insulin geometric mean, 7.1 versus 4.7 microU/ml, and 2-h insulin, 37.3 versus 14.1 microU/ml, respectively). There were no significant ethnic differences in the mean concentrations of fibrinogen, factor VII, von Willebrand factor, or fibrin D-dimer (P > 0.10). However, the t-PA antigen concentration was significantly elevated in South Asians compared with Europeans (mean, 10.6 versus 8.2 ng/ml, P = 0.001). t-PA correlated positively in both ethnic groups with features of the metabolic syndrome but the ethnic difference in t-PA persisted after adjustment for adiposity, metabolic and inflammatory variables (beta = 2.0, 95% confidence interval = 0.5-3.6, P = 0.012). We therefore hypothesize that elevated t-PA antigen may be a novel mechanism contributing to increased cardiovascular risk in South Asians.
 ...
PMID:Specific elevation in plasma tissue plasminogen activator antigen concentrations in South Asians relative to Europeans. 1461 56

Testicular cancer patients have an increased risk for coronary artery disease more than ten years after cisplatin-based chemotherapy. We investigated whether vascular changes, including endothelial dysfunction, are present earlier. Ninety chemotherapy-treated testicular cancer patients (median follow-up of seven years) were compared with 44 patients after orchidectomy only and 47 healthy men. Microalbuminuria was present in 10 (12%) chemotherapy patients, one stage I patient and none of the controls. Chemotherapy patients had higher levels of fibrinogen, C-reactive protein (hs-CRP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Chemotherapy patients with elevated PAI-1 (25/90) showed clustering of cardiovascular risk factors resembling the metabolic syndrome. In conclusion, cured testicular cancer patients showed a high prevalence of microalbuminuria and increased plasma levels of endothelial and inflammatory marker proteins, which might progress to more severe endothelial dysfunction and overt atherosclerosis.
 ...
PMID:Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer. 1501 71

The metabolic syndrome, in which insulin resistance is the core feature, is associated both with dysregulation of thrombosis/fibrinolysis and erythrocyte sodium/lithium countertransport (SLC). To investigate this further we designed a cross-sectional study to examine whether factors involved in coagulation- and fibrinolysis systems were associated with SLC independently of insulin resistance in 93 58-year-old men. SLC was in univariate analysis positively correlated with PAI-1 activity (r = 0.35, p <0.01), tPA antigen (r = 0.38, p <0.01), von Willebrand factor (r = 0.25, p <0.05), protein S (r = 0.26, p <0.05), and C (r = 0.30, p <0.01), and negatively associated with tPA activity(r = -0.28, p <0.01). Since these correlations could be influenced by the components of the metabolic syndrome itself, a separate analysis with adjustment for glucose infusion rate (GIR), plasma insulin, body fat, sagittal diameter of the abdomen (SD) and log serum triglyceride concentration (TG) was conducted. Then SLC was associated with tPA antigen independent of GIR, plasma insulin, body fat, SD and TG. SLC was also associated with protein C independent of GIR, insulin, body fat and SD but not TG. In conclusion, we found a relationship between SLC and the fibrinolytic system that was not related to the metabolic syndrome.
 ...
PMID:Erythrocyte sodium/lithium countertransport is associated with thrombotic and fibrinolytic factors in 58-year-old men. 1517 2

Although the metabolic syndrome is associated with endothelial damage/dysfunction, the effect of risk factors and their relationship with the development of this condition are unclear. We hypothesized that plasma von Willebrand factor (vWf, marking endothelial damage/dysfunction) increases with the number of components of metabolic syndrome and that increased levels precede its development. To test this, fasting vWf, glucose and lipids were measured in 161 patients (mean age 63 +/- 7 yr, 85% males) with hypertension. Using World Health Organization (WHO) criteria, 32 (19.9%), and using National Cholesterol Education Program (NCEP) criteria, 70 (43.5%) had metabolic syndrome. Plasma vWf was higher in these patients regardless of defining criteria and increased with the number of the components of metabolic syndrome (both P < 0.001). After 4 yr, patients who did not have metabolic syndrome at baseline were reassessed for the development of this condition. Of the 129 patients who did not meet the WHO criteria at baseline, 38 (29.5%) subsequently developed the condition, whereas 36 of the 91 (39.6%) who did not meet the NCEP criteria at baseline subsequently developed metabolic syndrome. Baseline vWf levels did not predict development of metabolic syndrome, regardless of criteria (P = 0.071 for WHO and P = 0.639 for NCEP). Our data suggest more severe endothelial damage/dysfunction with cumulative metabolic syndrome-related risk factors. The failure of plasma vWf to predict the development of metabolic syndrome suggests that endothelial damage/dysfunction is a consequence, not a cause, of these risk factors.
 ...
PMID:Plasma von Willebrand factor and the development of the metabolic syndrome in patients with hypertension. 1553 84

An increased amount of deep abdominal visceral fat has generally been accepted as an important cardiovascular risk factor, and disturbances in hemostasis and fibrinolysis have been suggested to play a role. Fibrinogen and von Willebrand factor, representatives of the hemostatic system, and plasminogen activator inhibitor 1 (PAI-1), as the most important inhibitor of the fibrinolytic system, have been associated with visceral obesity, with the most convincing evidence found for the involvement of PAI-1. The association with fibrinogen and von Willebrand factor has been suggested to be merely a reflection of the association with inflammation and endothelial dysfunction. The fact that PAI-1 is secreted by adipose tissue has attracted much attention. The increase of PAI-1 in visceral obesity could be because visceral adipose tissue produces more PAI-1 compared with subcutaneous abdominal adipose tissue. The contribution of other cell types such as hepatocytes or endothelial cells is probably more important, with stimulation of PAI-1 production by different components of the metabolic syndrome. PAI-1 secretion by adipose tissue has been suggested to have a more local effect, playing a role in tissue remodeling during the development of obesity.
 ...
PMID:Visceral fat as a determinant of fibrinolysis and hemostasis. 1596 80

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.
 ...
PMID:Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients. 1609 34

Patients with type 2 diabetes and abdominal fat patterning displayed higher plasma activities of clotting factors VII and VIII as well as increased plasma levels of fibrinogen and von Willebrand factor antigen, when compared with not only healthy normal weight controls, but also with diabetic patients at normal body weight. Mechanisms associating abdominal obesity with the above mentioned prothrombotic changes are only partially elucidated and may differ according to the individual haemostatic variable. Actually, according to data in the literature and authors' observations increased plasma factor VII activity is mainly associated with increased plasma triglyceride level, while the hepatic synthesis of fibrinogen as well as the synthesis and release of endothelia-derived von Willebrand factor are stimulated by cytokines originating in the visceral adipose tissue. The relationship between the presently investigated hemostatic variables and features of the metabolic syndrome are less obvious than in the previously recorded association of metabolic risk factors with plasma levels of plasminogen activator inhibitor.
 ...
PMID:Effect of abdominal obesity on prothrombotic tendency in type 2 diabetes. Behavior of clotting factors VII and VIII, fibrinogen and von Willebrand Factor. 1673 71


1 2 3 Next >>