Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. 762 4

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.
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PMID:Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects. 808 57

Microalbuminuria is an important risk factor for cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) patients although the pathogenic mechanism between microalbuminuria and cardiovascular disease has not yet been established. Microalbuminuria in insulin-dependent diabetes mellitus (IDDM) patients has been related to abnormalities in haemostasis, poor glycaemic control, disadvantageous alterations in the lipid spectrum and elevated concentrations of lipoprotein(a), another independent risk factor for cardiovascular disease. In this study the interrelations between microalbuminuria and metabolic control, lipoprotein(a), other blood lipids and several haemostasis parameters were studied in 96 NIDDM patients (50 women, 46 men). Forty-three patients showed microalbuminuria. No significant differences were found in blood lipids (Lp(a), serum cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides), glycaemic control (HbA1c) and several haemostasis parameters (factor VII, VIII, fibrin monomer, thrombin-antithrombin III, D-dimer, tissue plasminogen activator antigen and plasminogen activator inhibitor-1) between the micro- and normoalbuminuric subgroups. In the microalbuminuric subgroup increased concentrations for plasminogen and alpha 2-antiplasmin were measured. In general, the presence of microalbuminuria was not associated with significant alterations in glycaemic control, blood lipids or haemostasis parameters in this group of 96 NIDDM patients. Further investigation is required to explain the excess cardiovascular mortality in patients with an elevated urinary albumin excretion rate.
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PMID:The effect of microalbuminuria on glycaemic control, serum lipids and haemostasis parameters in non-insulin-dependent diabetes mellitus. 825 Apr 95

Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD) in insulin-dependent diabetes mellitus (IDDM) patients, but the pathophysiological basis of this association is not clear. To see whether or not hemostatic dysfunctions might contribute to explain this association, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), factor VII activity, plasma fibrinogen, and plasma endothelin-1 (ET-1) in 13 microalbuminuric (albumin excretion rate [AER], 20-200 micrograms/min) and in 13 comparable normoalbuminuric (< 20 micrograms/min) IDDM patients. t-PA and ET-1 were similar in the two groups, whereas PAI-1 activity (5.65 +/- 1.92 vs. 0.85 +/- 0.58 IU/ml, P < 0.05), factor VII (87.85 +/- 4.94 vs. 76.54 +/- 2.31%, P < 0.05), and plasma fibrinogen (3.38 +/- 0.21 vs. 2.65 +/- 0.13 g/l, P < 0.05) were significantly higher in microalbuminuric than in normoalbuminuric patients. Plasma fibrinogen was related to AER (r2 = 0.23, P < 0.05), whereas triglycerides and factor VII were related to PAI-1 (r2 = 0.39, P < 0.001 and r2 = 0.10, P < 0.05). These results suggest that microalbuminuria is associated with a hypercoagulative and hypofibrinolytic state. Hemostatic dysfunctions might be a pathogenetic link between microalbuminuria and CVD.
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PMID:PAI-1 and factor VII activity are higher in IDDM patients with microalbuminuria. 831 15

Factor VII (FVII) is a plasma vitamin K-dependent glycoprotein that plays an important role in the initiation of tissue factor-induced coagulation (extrinsic pathway of blood coagulation). An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. Recently, the coagulation assay using soluble tissue factor(sTF) enables us to measure the plasma levels of the activated form of factor VII(FVIIa) without the effect of the FVII zymogen form. We have developed the fluorogenic assay for FVIIa using sTF and measured the plasma FVIIa in atherosclerotic diseases. The FVIIa level in the Japanese was lower than that reported in Caucasians, suggesting that the incidence of ishemic heart disease is lower in the former. The FVIIa level was higher in the patients with cardiovascular diseases (ischemic heart disease and cerebral infarction), non-insulin-dependent diabetic mellitus, hypertension with microalbuminuria, and renal failure than in the healthy controls. The FVIIa levels were also increased in non-insulin-dependent diabetic patients, and this FVIIa increase was positively correlated with urinary albumin excretion. Furthermore, FVIIa levels were not correlated with the levels of lipids and the activity of hepatic synthesis, indicating that FVIIa may be an independent risk factor for cardiovascular disease.
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PMID:[Activated factor VII as a new cardiovascular risk factor of atherothrombotic disease]. 856 29

We studied the relationship among albuminuria, factor VII (FVII) hyperactivity, and endothelial cell damage in 6 elderly hypertensive subjects. The plasma levels of activated FVII (FVIIa), FVII coagulant activity, FVII antigen (FVIIag), von Willebrand factor (vWF), and thrombomodulin were measured to assess FVII hyperactivity and endothelial cell damage, and urinary albumin excretion rate (UAE) was calculated using 12-hour nighttime (7 pm to 7 am) urine collection (mean for 2 consecutive nights). We performed 24-hour ambulatory blood pressure monitoring in all 61 hypertensive patients and classified them into a white-coat hypertension group (n=12) and a sustained hypertension group (n=49). For the levels of FVII, vWF, and thrombomodulin, there were no differences between the white-coat hypertension group and normotensive control subjects (n=25). In the sustained hypertensive group, only the microalbuminuric subgroup (UAE, 15 to 300 microgram/min: n=30) showed significant elevation compared with the normotensive group for the level of FVIIa (mean [95% confidence interval]: 4.0 [3.6 to 4.4] versus 3.0 [2.6 to 3.3] ng/mL, P<.001), the FVIIa/FVIIag ratio (an indicator of activation of FVII zymogen to FVIIa) (1.33 [1.19 to 1.50] versus 1.04 [0.92 to 1.19], P<.01), the level of vWF (188 [165 to 214] % versus 144 [129 to 160] %, P<.01), and thrombomodulin (11.7 [10.3 to 13.3] versus 9.3 [8.5 to 10.3] ng/mL, P<.01). In contrast, none of these levels in the normoalbuminuric hypertensive group (UAE <15 microgram/min, n=19) differed from that in the normotensive control group. These results suggest that among elderly hypertensives, only those with microalbuminuria show enhancement of FVII activation and endothelial cell damage, while patients with white-coat hypertension and normoalbuminuric hypertensives do not show these accompanying abnormalities. Thus, increased levels of FVII activity and markers of endothelial cell damage might account for the higher risk of cardiovascular events in essential hypertension with microalbuminuria.
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PMID:Factor VII hyperactivity and endothelial cell damage are found in elderly hypertensives only when concomitant with microalbuminuria. 863 Jun 73

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