Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is increased 2- to 4-fold in non-insulin-dependent diabetes mellitus (NIDDM); yet in most studies, there is a relatively weak relationship between the frequency of coronary heart disease (CHD) and the duration of diabetes and severity of hyperglycaemia. A number of authors have suggested that the prediabetic stage may contribute to the risk of CHD in NIDDM. Hyperinsulinaemia and insulin resistance have been strongly associated with the development of NIDDM. Data are less conclusive about the relationship of hyperinsulinaemia to the development of CHD in nondiabetic subjects. Relatively little data are available on hyperinsulinaemia and/or insulin resistance to CHD in NIDDM subjects. Tight control of glycaemia with exogenous insulin improves cardiovascular risk factors in NIDDM subjects and therefore is unlikely to increase the risk of CHD. Although the relation of insulin to CHD in the general population is somewhat controversial, insulin is clearly related to multiple cardiovascular risk factors (especially elevated triglyceride, decreased high-density lipoprotein, small dense low-density lipoprotein, impaired glucose tolerance and increased plasminogen activator inhibitor 1 (PAI-1)). However, the relation of insulin resistance to hypertension remains controversial.
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PMID:Cardiovascular risk factors and the prediabetic syndrome. 886 92

Thirteen patients with mild hypertension (untreated diastolic blood pressure of 95 to 114 mmHg) received, in random order, three successive treatments of four weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg daily). At the end of each treatment, blood samples for assessment of platelet aggregation and platelet release of platelet factor 4 (PF4) and for assessment of fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were taken, first at rest, then immediately after five to ten minutes of vigorous exercise, and finally after the subsequent hour of recovery rest. Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with placebo (P < 0.05) at rest, and the threshold for adenosine diphosphate (ADP) aggregation also rose, from 2 microM to 4 (NS). The resting plasma PF4 value fell, although not significantly, during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sampled at rest, and the PF4 plasma levels showed no significant reductions at rest. However, during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy. This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo (P < 0.05). ECLT and t-PA did not shift significantly from the placebo level during either therapy. PAI-1 did not change during spirapril therapy, but during HCT2 treatment it fell, although not significantly, to 9.36 IU/mL from 15.91 with placebo (NS). Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis. HCT2 seems to decrease platelet activity at rest, whereas spirapril seems to some extent to decrease platelet activity at exercise.
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PMID:Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension. 887 80

To assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated in the progeny of young coronary men, 193 young subjects were recruited and divided into two groups. Group A consisted of 104 children whose fathers had suffered a myocardial infarction before the age of 55 ("cases"). Eighty-nine young subjects matched for age, sex, body mass index (BMI) and smoking habits without familial history of coronary artery disease (CAD) served as controls (group B). Children with a family history of diabetes mellitus or hypertension were excluded from both groups. We measured PAI-1 activity, tissue-type plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and apolipoproteins in both groups. PAI-1 activity levels were also determined in the men who suffered a premature myocardial infarction 4 months after their discharge. PAI-1 activity levels were higher in cases compared to controls (3.13 +/- 1.9 vs 2.17 +/- 1.9 U/ml, p = 0.0014). t-PA antigen and a2-antiplasmin did not differ significantly between the two groups, while fibrinogen, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) were significantly higher in group A. PAI-1 was positively correlated with triglycerides (r = 0.22, p = 0.024), apolipoprotein B (r = 0.21, p = 0.039) and fibrinogen (r = 0.22, p = 0.029) in cases and with BMI in both cases (r = 0.37, p = 0.0003) and controls (r = 0.23, p = 0.044). In stepwise multiple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p = 0.0014) were significant determinants of PAI-1 activity in cases. There was also a positive correlation between PAI-1 activity levels of the affected fathers and their children (r = 0.30, p = 0.01). The present data support the hypothesis that elevated PAI-1 levels in the offspring of men with premature myocardial infarction impair their fibrinolytic capacity contributing to their familial predisposition to CAD.
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PMID:Plasminogen activator inhibitor 1 is elevated in the children of men with premature myocardial infarction. 888 80

Epidemiological studies show that serum uric acid is positively associated with blood pressure levels and that serum uric acid is also a predictor of the development of hypertension in normotensive adults. Several clinical studies revealed that insulin resistance and/or hyperinsulinaemia is associated with hypertension and higher plasma concentrations of uric acid, triglyceride and plasminogen activator inhibitor 1 and with lower HDL cholesterol concentrations. Abnormalities in membrane transport system of sodium and related ions may be associated with impared urinary excretion of uric acid in hyperuricemic patients with hypertension. Several anti-hypertensive drugs have been shown to increase urinary excretion of uric acid and thereby reduce its serum level. Strict salt restriction and weight loss may cause at least in the short-term, adverse metabolic changes including elevated uric acid levels. In hypertensive patients.
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PMID:[Hypertension and hyperuricemia]. 897 6

1. In the present study, endothelial cells (EC) growth and fibrinolytic activity of WKY/Izm and SHRSP/Izm were investigated in vitro. 2. EC were isolated from the thoracic aortas of WKY and SHRSP at the age of 8-9 weeks. Proliferative activities of EC were analysed with doubling time and DNA synthesis. Fibrinolytic activity was determined by tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) activities in cultured medium. 3. SHRSP-EC growth rate was significantly greater than WKY-EC growth rate in doubling time. In the assay for DNA synthesis, 5-bromo-2'-deoxy uridine incorporation rate in SHRSP-EC was significantly increased compared with that in WKY-EC. 4. The tPA activity in cultured medium of WKY-EC was 2-fold greater than that of SHRSP-EC, while PAI-1 activities were nearly equal in them. 5. These physiological distinctions of EC of SHRSP/Izm from that of WKY/Izm with close genetic background could be contributory genetic factors to hypertension-related vascular diseases in SHRSP.
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PMID:Distinction of endothelial cell growth and fibrinolytic activity between WKY/Izm and SHRSP/Izm in vitro. 907 87

Impaired fibrinolysis due to elevated levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic disease. Hypertension, obesity, derangements in lipid and glucose homeostasis, and elevated levels of PAI-1 are features of the insulin resistance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin resistance syndrome in 53 men and 31 women with untreated hypertension. In men, PAI-1 activity correlated significantly with plasma glucose (r = .41, P = .002), insulin sensitivity (r = -.35, P = .01), and insulin-induced suppression of nonesterified fatty acid (NEFA) (r = -.43, P = .007). Plasma glucose and NEFA suppression were independently associated with PAI-1 activity in a multivariate analysis. In women, PAI-1 activity correlated with body mass index (r = .62, P = .0005), waist-to-hip ratio (r = .75, P = .0001), plasma glucose (r = .50, P = .007), insulin (r = .49, P = .009), proinsulin (r = .57, P = .002), C-peptide (r = .60, P = .0009), insulin sensitivity (r = -.74, P = .0001), NEFA suppression (r = -.64, P = .003), and triglycerides (r = .58, P = .001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist-to-hip ratio was not included in the model. After introduction of waist-to-hip ratio into the model, waist-to-hip ratio was the only independent predictor of PAI-1 activity. We conclude that in women, waist-to-hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppression and plasma glucose are independently associated with PAI-1 activity.
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PMID:Gender differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension. 910 76

Twenty-three insulin-dependent diabetics with proteinuria (3.3 g/day: range 0.3 to 8.9) and azotemia (creatinine clearance: 58 mL/min, range 30 to 112) were tested for 24-h mean arterial blood pressure; instantaneous heart rate variations to a computerized protocol involving timed ventilation, assumption of upright posture, and Valsalva maneuver; plasma fibrinogen, viscosity, fibrinolytic activity, and plasminogen activator inhibitor. These were to test the hypothesis that autonomic dysfunction is associated with altered concentrations of plasma fibrinogen, fibrinolytic activity, viscosity, and plasminogen activator inhibitor. We have previously shown the absence of a correlation between level of blood pressure, clinical and standard laboratory testing, and the results of the autonomic function testing protocol used in this study. In this group of patients, plasma fibrinogen concentration was correlated (positively) with mean arterial pressure and (negatively) with heart rate variation in response to the Valsalva maneuver. The greater the mean arterial pressure or the worse the Valsalva results, the higher the plasma fibrinogen concentration. In addition, patients with one or no abnormal autonomic function tests had a mean fibrinogen of less than 400 mg/dL compared to the group of patients with two or more abnormal tests who had a mean fibrinogen of 500 mg/dL. In patients with demonstrated parasympathetic abnormalities, postural heart rate variation testing also discerned a differential in plasma fibrinogen. Lower concentration of plasminogen activator inhibitor throughout the day, and greater fibrinolytic activity in the morning were also noted to be present in patients with abnormal heart rate response to the Valsalva maneuver. We conclude that there are relationships between high blood pressure, autonomic function, and hemostatic factors favoring thrombogenesis that may be related by common mechanisms and treatments in the diabetic with kidney disease.
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PMID:Relationship between autonomic function and plasma fibrinogen, viscosity, and elements of fibrinolytic activity in diabetic nephropathy. 912 13

Hypertension is associated with derangements in glucose and lipid metabolism. Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to potentiate the development of coronary events in this condition. Fish oil (omega3 polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the cardioprotective potential has been questioned because fish oil has been found to increase PAI-1 activity. This study was performed to determine the effects of omega3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons with untreated hypertension were included in a 16-week, double-blind, randomized, controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator (tPA) activity, levels of fibrinogen and factor VII(c), and platelet count were measured before and after intervention (mean+/-SE). PAI-1 activity changed similarly in the fish oil and corn oil groups (1.8+/-1.0 U/mL versus 3.5+/-1.2 U/mL, P=.25), as did tPA (-0.02+/-0.02 IU/mL versus -0.13+/-0.03 IU/mL, P=.28), levels of factor VII(c) (6+/-5% versus 5+/-4%, P>.3), and platelet count (2+/-7x10(9)/L versus 3+/-5x10(9)/L, P>.3). None of these variables changed from pretreatment levels during fish oil intake. Fibrinogen levels increased significantly both during fish oil (0.6+/-0.1 g/L, P=.0001) and corn oil (0.4+/-0.1 g/L, P=.002) intake. There was no between-group difference (P>.3). In conclusion, a daily intake of 4 g omega3 PUFAs does not affect PAI-1 and tPA activity in persons with hypertension. A modest increase in fibrinogen levels was observed after both fish oil and corn oil intake.
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PMID:Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids. 915 42

Vascular cell adhesion molecule-1 (VCAM-1) is a protein expressed on the surface of activated endothelial cells and expressed in early atherosclerosis. Because part of the protein is shed in the circulation and can be detected in peripheral plasma [soluble (s) VCAM-1], we hypothesized that sVCAM-1 may be a circulating marker of the presence and severity of atherosclerosis in humans. We selected 11 patients with essential hypertension plus peripheral vascular disease (PVD) and matched them for age, gender, body mass index, and smoking habits with 11 patients with uncomplicated essential hypertension (UH) and 11 healthy controls. We evaluated plasma concentrations of sVCAM-1 along with those of the soluble form of two other endothelial leukocyte adhesion molecules [sE-selectin and s-intercellular adhesion molecule-1 (sICAM-1)] and other markers of endothelial dysfunction/ damage [s-thrombomodulin, plasminogen activator inhibitor type I, and von Willebrand factor (vWF)]. We also measured insulin, glucose, fibrinogen, total and HDL cholesterol, and the urinary albumin excretion (UAE), which may also be related to atherosclerosis. Results of these assays were related to the echographic assessment of the maximum intima-media thickness (IMTmax) at the carotid bifurcation, as an index of atherosclerosis in the carotids. PVD patients had a clearly elevated IMTmax [2.7 (1.1-3.1) mm, median (range)] compared with both UH patients [1.2 (0.8-2.4) mm] and controls [1 (0.6-2) mm]. sVCAM-1 was clearly higher in PVD patients [990 (273-1808) ng/mL, median (range)] versus 340 (236-975) ng/mL in UH and 386 (204-835) ng/mL in controls, and it separated clinical categories better than sICAM-1, vWF, glucose, insulin, UAE, triglycerides, or total, LDL or HDL cholesterol, sVCAM-1 was also the best biohumoral correlate of IMTmax (R = .59; P < .001) in univariate analysis. Because many of the biohumoral variables assessed were mutually intercorrelated, they were entered in a multivariate analysis to assess their contribution in explaining IMTmax variability. sVCAM-1 remained the only independent predictor of IMTmax and totally abolished the contribution of other variables to IMTmax variability. Thus, sVCAM-1 is a good biohumoral correlate of overt atherosclerosis, independent of underlying hypertension, and may be an in vivo marker of endothelial activation. Its potential value as a surrogate for global risk assessment and its behavior in intervention studies remain to be determined.
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PMID:Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis. 940 38

Although the arterial tree is exposed to increased pressure in hypertensive patients, paradoxically, the complications of hypertension (heart attacks, stroke) are mainly thrombotic rather than hemorrhagic. Patients with left ventricular (LV) hypertrophy are at high risk of the complications of hypertension. We performed a cross-sectional study of 178 patients attending a hypertension clinic in a city center teaching hospital, and measured plasma levels of the soluble adhesion molecule P-selectin (associated with platelet activity/function and atherosclerosis), the von Willebrand factor (vWf; a marker of endothelial dysfunction), fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor (PAI, an index of fibrinolysis), lipoprotein(a) (Lp(a), associated with thrombogenesis and atherogenesis) and hemorheological indexes (fibrinogen, hematocrit, plasma viscosity, hemoglobin) in patients with essential hypertension, in whom the LV mass and LV mass index were determined using echocardiography. The 178 patients (86 men, mean age 54 +/- 15 years) were compared with 47 normotensive healthy controls (aged 56 +/- 20 years). Hypertensive patients had higher P-selectin, PAI, vWf, fibrin D-dimer, Lp(a), plasma fibrinogen, and plasma viscosity when compared with controls. Black hypertensive patients had higher Lp(a) levels and LV septal and posterior wall thickness on echocardiography, but lower plasma PAI levels. Patients with LV hypertrophy (defined as a LV mass index > 134 g/m2 in men or > 110 g/m2 in women) had higher plasma fibrinogen compared with those without LV hypertrophy. Systolic blood pressures were significantly correlated to age, plasma viscosity, plasma fibrinogen, and vWf. Diastolic blood pressures were significantly correlated with age and plasma fibrinogen. Fibrinogen levels were correlated with LV mass, LV mass index, left atrial size, plasma viscosity, and vWf. Fibrin D-dimer levels were significantly correlated with vWf and fibrinogen levels. Thus, hypertensive patients have high plasma fibrinogen levels, thrombogenesis, and impaired fibrinolysis (as indicated by high D-dimer and PAI levels, respectively), platelet activation (raised soluble P-selectin), and endothelial dysfunction (high vWF). The high plasma fibrinogen levels were related to blood pressures, LV mass index (and LV hypertrophy), and left atrial size. These abnormalities in hemorheologic factors and markers of thrombogenesis and endothelial function may act synergistically to increase the risk of thrombogenesis and atherosclerosis in hypertensive patients.
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PMID:Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy. 941 37


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