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

Assessment of the risks of new antithrombotic therapies is best undertaken by evaluating risk factors for bleeding in individual patients, and risks associated with specific antithrombotic agents. This forms the basis for the development of a management strategy for major bleeding complications. Patient-related risk factors for bleeding with oral anticoagulants include: trauma, invasive procedures, history of bleeding disorder, high anticoagulant intensity, concomitant use of antiplatelet drugs, presence of underlying severe disease, advanced age, and prior history of cerebrovascular accident, or gastrointestinal bleeding. Weight-adjusted and other nomograms are more successful in achieving a balance between therapeutic effect and safety with intravenous heparin. The most important complication of thrombolytic therapy is intracranial haemorrhage, and the risks increase with age > 65 years, weight under 70 k, hypertension on admission and the use of tissue plasminogen activator: this profile is helpful in assessing risk-benefit ratio amongst individual patients. Recent experience with the experimental use of antithrombin agents such as hirudin, indicates a delicate dose-response relationship as it relates to the risk of cerebral haemorrhage, when used in conjunction with thrombolytic agents. A definitive answer regarding the role of hirudin and the balance of safety and efficacy awaits completion of ongoing trials. Novel IIb/IIIa platelet inhibitors appear to offer a significant therapeutic advance: major bleeding is variable and depends in part on the use of concomitant procedures, and heparin therapy. It is important to identify the source and severity of bleeding with the use of antithrombotic therapy and its haemodynamic consequences in constructing a management plan. Well developed treatment algorithms for patients with severe bleeding exist, and although laboratory testing may be helpful, it is on balance of marginal benefit since patients usually require urgent therapy. Future investigation promises more readily available, rapid and specific laboratory testing, and newer antithrombotic agents that are easier to administer and monitor. Molecular targeting with fusion proteins that attract to a specific antigen, thereby delivering more effective and safe therapy, offer new promise.
 ...
PMID:Bleeding risks, risk factors and management of bleeding complications after treatment with anticoagulants, specific antithrombins, thrombolytics IIb-IIIa receptor blockers. 886 23

Prothrombin activation fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III complexes (TAT) were measured in plasma of 34 patients with newly diagnosed essential hypertension. The patients with hypertension showed an increase in both F1 + 2 and TAT concentrations. The obtained results point to the intravascular thrombin generation in very early stages of essential hypertension.
 ...
PMID:Prothrombin activation fragment 1 + 2 and thrombin-antithrombin-III complexes in plasma of patients with essential arterial hypertension. 911 58

It has been suggested that the hypercoagulable state in severe preeclampsia is strongly related to the onset of intrauterine growth retardation (IUGR) through the deterioration of placental circulation. In this study, one of two kinds of anticoagulants, heparin or antithrombin (AT), was given to severe early-onset preeclamptic women (onset before 32 weeks of gestation) with IUGR, and the efficacies in maternal and fetal findings were compared. The mechanism of AT to improve placental circulation was discussed based on our previous study using the culture system of chorionic trophoblastic cells. The mean systolic blood pressure decreased significantly in the AT group (AT concentrate 1,500 IU/d for 7 days, n = 15). Fetal growth was calculated by ultrasonographic measurement, and the weight gain was higher in the AT group than it was in the heparin group. In vitro experiments showed that AT increased the thrombomodulin (TM) antigen on the cell surface and also increased prostaglandin I2 (PGI2) production by cultured trophoblastic cells. This suggests that AT replacement therapy is useful for improving maternal hypertension and fetal findings in severe preeclampsia with IUGR through the increase of TM and PGI2 production in both maternal and placental circulation.
 ...
PMID:Efficacy of antithrombin replacement therapy in severe early-onset preeclampsia. 1062 3

Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.
 ...
PMID:Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study. 1066 53

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.
 ...
PMID:Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene. 1093 9

Increased plasma fibrinogen levels and hemostatic abnormalities suggestive of a prothrombotic state are present in patients with end-stage renal failure and could contribute to increased cardiovascular morbidity in these patients. We investigated the relationship between abnormalities of the hemostatic system and the degree of renal failure and whether these abnormalities are associated with increased prevalence of cardiovascular events in patients with arteriolar nephrosclerosis. In 425 patients recruited at a hypertension clinic we assessed the renal function by creatinine clearance, urinary protein excretion, and microalbuminuria, the prevalence of atherosclerotic disease, and measured prothrombin time, activated partial thromboplastin time. fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, and antithrombin. Early impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) caused by arteriolar nephrosclerosis was found in 172 patients. Patients with early renal failure were significantly older and had significantly greater values of blood pressure, plasma fibrinogen, F1+2, and D-dimer than patients with normal renal function. Elevated D-dimer and fibrinogen levels were independently associated with the presence of decreased creatinine clearance. Log fibrinogen, log F1+2, and log D-dimer were inversely correlated with creatinine clearance. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was significantly greater in patients with mild renal failure than in those with normal renal function. Elevated levels of fibrinogen and D-dimer were associated with the presence of atherosclerotic disease independent of renal function and other risk factors. In conclusion, changes in hemostatic parameters occur early in the course of renal failure in patients with arteriolar nephrosclerosis, suggesting a prothrombotic state that may contribute to the risk for atherosclerotic disease at all levels of renal function.
 ...
PMID:Increased fibrinogen levels and hemostatic abnormalities in patients with arteriolar nephrosclerosis: association with cardiovascular events. 1105 51

Placental abruption is due to the rupture of the uterine spiral artery. The placenta separates totally or partially from the uterine wall during pregnancy. This serious syndrome has a great risk for the mother (shock and disseminated intravascular coagulation) and her child (mortality or morbidity). To the known risk factors like hypertension, the use of cocaine and smoking, homocysteine is recognized as an independent risk factor for vascular disease and endothelial dysfunction. In contrast to normal pregnancy where the spiral artery endothelium is replaced by trophoblast, the endothelium persists in case of placental abruption. In 165 women with placental vasculopathy and 139 matched controls hyperhomocysteinemia resulted in an odds ratio of 4.7 (95% CI: 1.6-14.0). The C677T mutation gave a risk of 2.5 (95% CI: 1.0-6.0). Even up to 2 or 3 years post-partum evidence could be found of endothelial dysfunction. The combination of hyperhomocysteinemia and thrombotic factors like APC resistance, Protein-C, Protein-S, antithrombin and factor V Leiden increases the risk of placental abruption 3-7 times. The common denominator of the effect of homocysteine on blood vessels could be sited in the process of proliferation of cells that need proper methyl groups for proper function (DNA synthesis and expression). These methyl groups are delivered by D-adenosylmethionine formed from methionine after remethylation of homocysteine. The coagulation factors and plasma homocysteine values can be modulated by vitamins, folic acid and folates in particular. To prove the clinical value of folate supplementation placebo-randomized trials are urgently needed: for placebo to be started after the period of neural tube closure.
 ...
PMID:Clotting disorders and placental abruption: homocysteine--a new risk factor. 1130 Nov 73

Oral contraceptive therapy (OCT) is widely used in the world. It is usually safe and effective but side effects are occasionally seen. Venous thromboembolism is one of the most feared side effects. To avoid this complication adequate guidelines are needed. These have to take into account family history, personal history, and suitable laboratory investigations. The presence of an idiopathic venous thrombosis in the family or in the personal history is of paramount importance. However it is often difficult to ascertain whether a venous thrombosis is idiopathic or not. Even when there is doubt, a coagulation study should be carried out. An adequate coagulation study in this case should include at least an evaluation of antithrombin, protein C, and protein S. A search for homozygosity of factor V Leiden appears advisable. These defects represent absolute contraindications to the use of OCT. Relative contraindications may be represented by other minor coagulation disorders such as heterozygous factor V Leiden, fibrinolysis defects, and a G-to-A 20210 prothrombin abnormality. Other noncoagulation-related conditions such as hypertension, liver damage, and obesity may represent absolute or relative contraindications to the use of OCT.
 ...
PMID:Tentative guidelines and practical suggestions to avoid venous thromboembolism during oral contraceptive therapy. 1212 Oct 63

Antihypertensive treatment reduces the risk of thromboembolic events in hypertension. The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension. Fibrinogen, thrombin-antithrombin complex (TAT) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks, or ramipril for 6 weeks or 6 months. Ramipril reduced resting TAT, and tended to reduce fibrinogen; Factor VII remained unchanged. Mental stress increased fibrinogen, but did not alter TAT or Factor VII activity. The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease.
 ...
PMID:Long-term angiotensin-converting enzyme inhibition with ramipril reduces thrombin generation in human hypertension. 1214 6

Benefits of high-dose progestational contraception (pregnanes [chlormadinone acetate] or norpregnanes, promegestone, nomegestrol acetate) are its anti-estrogenic effect and its overall absence of metabolic effects. It lowers apoprotein A1 and increases antithrombin 3, but these changes produce no adverse effects. High-dose progestational contraception is ideal for women with certain contraindications to combined oral contraceptive use: high blood pressure, hyperlipemia, diabetes mellitus, benign breast disease, and premenstrual tension. It inhibits ovulation. Nomegestrol acetate also changes the cervical mucus, making it inhospitable to sperm. The primary side effect of high-dose progestational contraception is menstrual cycle disturbances. A study of 5 mg nomegestrol acetate among women aged 19-40 used for 20 days of each 28 day cycle revealed no pregnancies. A preliminary study shows that transdermal administration of nomegestrol acetate and estradiol 17 beta adequately treats hypoestrogeny. In conclusion, high-dose progestational contraception produces excellent metabolic results and reduces clinical manifestations of hyperestrogeny.
 ...
PMID:[High-dose progestational contraception: advantages]. 1231 10


<< Previous 1 2 3 4 5 6 Next >>