UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Besides the thrombolytic therapy several adjuvant therapeutic measures were identified which significantly improve the prognosis of patients with acute myocardial infarction (AMI). These measures include the treatment by means of acetylsalicylic acid (ASA), beta-blockers and ACE inhibitors. Early administration of ASA and beta-blockers are indicated in all patients with AMI who have no contraindications for this therapy. They are especially the patients with manifest heart failure or asymptomatic left ventricular dysfunction who benefit from ACE inhibitors. The effectivity of routine administration of other medicaments such as anticoagulants, nitrates, calcium channel blockers and magnesium, have not been convincingly proved. However, some selected patients with AMI can benefit from these medicaments. Intravenous administration of heparin is unambiguously justified only in thrombolysis with t-PA. Thrombolyses with streptokinase, urokinase, and anistreplase are justified only at high risk of thromboembolic complications. Their prevention and therapy include also the necessity to restrict the administration of pelentan. The use of nitrates is indicated in patients with AMI in case of sustaining stenocardia, arterial hypertension and manifest heart left ventricular failure. Until the definitive standpoint is gained regarding the effect of magnesium in patients with AIM, its administration remains especially indicated in cases of arterial hypertension, tachycardiac disturbances of the heart rhythm and states of assumed or proved hypomagnesiemia. In AMI cases when magnesium is used in order to protect the patient from reperfusion lesion, it must be administered prior to the reperfusion therapy. An intensive research in the field of therapeutical measures in patients with AMI still continues. It is certain that it will soon bring further knowledge which will in turn improve the prognosis and quality of life of patients with AMI. (Tab. 4, Ref. 133.)
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PMID:[Adjuvant therapy in patients with acute myocardial infarct]. 892 11

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

In recent years, a prodigious amount of information has been gathered regarding the relationship between vascular biology and the mechanisms underlying cardiovascular disease. Activation of elements of the reninangiotensin system (RAS) appear to play an important role in the development and progression of conditions such as hypertension, coronary artery disease, and heart failure. Indeed, converging lines of evidence indicate that angiotensin-converting enzyme (ACE) regulates a delicate balance among a multitude of factors responsible for vascular tone, cellular growth promotion and inhibition, and pro- and anti-inflammatory effects. Because angiotensin II inhibits fibronectin, stimulates expression of plasminogen activator inhibitors, and degrades bradykinin, thereby impairing production of nitric oxide, ACE and the RAS are also involved in thrombosis and fibrinolysis. The favorable effects of ACE inhibition on endothelial function and, potentially, on cardiovascular morbidity and mortality are believed to result not only from angiotensin II suppression but also its consequent bradykinin preservation and nitric oxide production.
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PMID:The integrated effects of angiotensin II. 912 15

We recently showed that muscarinic receptor stimulation causes a marked increase in the net release of tissue-type plasminogen activator (TPA) antigen and activity across the human forearm in vivo, in conjunction with endothelium-dependent vasodilation. Because hypertension has been associated with endothelial dysfunction, the aim of the study was to compare forearm TPA release and vasodilation in response to muscarinic stimulation in normotensive (NC) and borderline hypertensive (BH) subjects. The study was performed in 10 apparently healthy young men with BH and 10 male NC subjects. Methacholine (MCh: 0.1, 0.8, and 4.0 micrograms/min) and sodium mitroprusside (SNP: 0.5, 2.5, and 10 micrograms/min) were administered in randomized order as double-blind, stepwise, intrabrachial artery infusions. Forearm blood flow was assessed by plethysmography. Net release/uptake was calculated as the product of the arteriovenous concentration gradient and forearm plasma flow. Vasodilator responses to MCh were similar in both groups (P = NS), whereas the decrease in forearm vascular resistance in response to SNP was somewhat less in BH subjects (P = .005). At rest, both groups showed a significant arteriovenous gradient and net release of TPA antigen across the forearm (P < .05 throughout). However, in contrast to the significant net increment in TPA activity across the forearm in the NC group (P < .018), BH subjects had no basal forearm increment in TPA activity (NC vs BH, P = .006). Arterial and venous plasma levels of plasminogen activator inhibitor 1 (PAI-1) antigen and activity were higher in BH subjects (P < or = .05 throughout), who in contrast to NC subjects, also had a significant forearm net release of PAI-1 antigen (P = .006). Across the whole group, there was a significant inverse relation between arterial PAI-1 antigen levels and increment in TPA activity across the forearm (r = -.57, P = .008) but no relation to TPA antigen release. In response to MCh infusion, both the net release of TPA antigen and increment in TPA activity increased markedly and to similar extents in both groups (P < .01 throughout). SNP infusion had no effect on either TPA antigen release or increment in TPA activity in the NC group but elicited a significant net release of TPA antigen and increase in TPA activity in the BH group (P < .05). Both circulating levels and local release of PAI-1 antigen were significantly correlated to fasting plasma insulin. Endothelium-dependent vasodilation and endothelial TPA release in response to muscarinic receptor stimulation were preserved in BH subjects. At rest, BH subjects had higher circulating PAI-1 antigen levels and a corresponding decrease in circulating levels and local increment of TPA activity. In contrast to NC subjects, BH subjects responded with a TPA release also in response to increased flow, which may indicate an enhanced endothelial cell responsiveness to fluid shear stress.
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PMID:Endothelium-dependent vasodilation and tissue-type plasminogen activator release in borderline hypertension. 943 82

Fibrinolytic therapy substantially reduces mortality from acute myocardial infarction. Patient selection is, however, important. The patient must present within 12 hours of the onset of ischaemic symptoms, have definite ECG changes of ST elevation or left bundle branch block and no contraindications. The major contraindications are those for risk of an intracerebral bleed, recent stroke, intracranial tumour or risk of a major systemic bleed. Age and hypertension are not contraindications but may modify the regimen used. Heparin is required with recombinant tissue plasminogen activator but is optional with streptokinase. The recent COBALT trial suggests that the accelerated weight related t-PA regimen given over 90 minutes is more satisfactory than double bolus t-PA. However, in patients under 75 years of age, the two regimens were equivalent. For patients suffering acute myocardial infarction, practitioners should now individualise choice of therapy, rather than give the same cocktail to all patients. The choice of regimen will depend on the cardiac risk, the stroke risk, the bleeding risk and the cost.
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PMID:The current status of thrombolytic therapy. 944 5

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Deletion polymorphism of angiotensin I-converting enzyme (ACE) gene has been reported to be an independent risk factor for myocardial infarction. Plasminogen activator inhibitor-1 (PAI-1) was proposed to be a link between the renin-angiotensin system and thrombotic risk. This study was undertaken to investigate the possible association between the insertion/deletion (I/D) polymorphism of the ACE gene and plasma PAI-1 levels in 160 patients with mild-to-moderate hypertension. The I/D genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Baseline levels of PAI-1 antigen and activity and tissue plasminogen activator (t-PA) antigen were determined in fasting morning plasma samples. It was found that patients with homozygote deletion (DD, n = 37) ACE genotype did not have significantly higher plasma levels of PAI-1 antigen (31.2 +/- 15.6 ng/mL v 28.4 +/- 15.1 ng/mL or 27.2 +/- 13.2 ng/mL, P = .42), PAI-1 activity (16.2 +/- 10.6 IU/mL v 14.1 +/- 9.4 IU/ mL or 15.0 +/- 9.9 IU/mL, P = .60), or t-PA antigen (14.6 +/- 6.0 ng/mL v 13.4 +/- 4.9 ng/mL or 14.6 +/- 5.7 ng/mL, P = .40) as compared to those with heterozygote (DI, n = 67) or homozygote insertion (II, n = 56) genotypes. On multiple regression analysis, the ACE genotypes did not appear to be significant predictors for plasma PAI-1 levels and t-PA antigen after adjustment with age, sex, body mass index, plasma triglyceride, cholesterol, and glucose. In conclusion, the results indicated that the I/D polymorphism of the ACE gene was not related to plasma PAI-1 levels in a Chinese population with hypertension. The ACE genotypes may not have a role in influencing the fibrinolysis in hypertension.
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PMID:Plasminogen activator inhibitor-1 and angiotensin I converting enzyme gene polymorphism in patients with hypertension. 952 54

Thromboembolic complications such as ischemic stroke and myocardial infarction are significantly more frequent in patients with arterial hypertension. From the available intervention studies, it appears that pharmacologic treatment of hypertension-at least with diuretics and beta-blockers-may more effectively protect against cerebrovascular as compared to coronary thromboembolic events. Whether other antihypertensive substances provide a more effective protection with respect to cardiac morbidity and mortality is the subject of numerous studies presently underway. These studies will help to answer the question of whether the extent of protection from coronary events during antihypertensive treatment depends on factors beyond blood pressure control. The fibrinolytic system is crucially involved in the pathogenesis of thromboembolic events. One determinant of this system is the balance between plasminogen activators (tissue-type plasminogen activator [t-PA]) and inhibitors (plasminogen activator inhibitor 1 [PAI-1]). Experimental and clinical evidence suggests that at least some of the drugs used in the treatment of hypertension may alter the activity of the fibrinolytic system. Scarce and controversial data with respect to such an interaction exist with respect to diuretics, beta-blockers, and calcium antagonists. In addition, experimental evidence demonstrates that PAI-1 is stimulated by angiotensin II (A II), whereas t-PA is activated by bradykinin. Thus, antihypertensive drugs acting within the renin angiotensin system should exert effects also within the fibrinolytic system. However, results from clinical studies with angiotensin converting enzyme (ACE) inhibitors and A II receptor antagonists do not unequivocally support such a concept. The discrepancy in the results may, at least in part, be explained by studies performed in healthy volunteer subjects showing that ACE inhibition profoundly affected fibrinolysis only during stimulation of the renin angiotensin system by NaCL restriction.
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PMID:Antihypertensive drug treatment and fibrinolytic function. 979 46

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