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)

The possibility that a circulating sodium pump inhibitor contributes to the pathogenesis of volume-dependent hypertension via an action on vascular smooth muscle (VSM) is supported by multiple lines of investigation, but remains controversial. We had two goals in this study. The first was to compare the pattern of contractile response of rabbit aorta induced by two candidates, ouabain and a labile sodium pump inhibitor that we have identified in the peritoneal dialysate of volume-expanded hypertensive patients with chronic renal failure. Our second goal was to examine the ability of Digibind, a Fab fragment of antisera directed against digoxin, to reverse VSM contraction induced by both agents. Ouabain induced a concentration-dependent contraction, which was delayed in onset, was gradual, and reached a stable plateau after many hours. The labile sodium pump inhibitor induced a qualitatively similar series of responses. Digibind rapidly reversed the contractile responses to both sodium pump inhibitors, with a rate of relaxation that matched that induced by physical removal of the pump inhibitor from the bath. For ouabain, the Digibind:ouabain stoichiometry was highly predictable. When Digibind was present in a molar concentration equivalent to that of ouabain, or less, it had no effect. When the Digibind concentration was twice that of ouabain, complete relaxation occurred. Although the concentration:VSM response relationship for ouabain was steep, the concentration:effect interaction with Digibind was even more steep. The molar concentration of Digibind required to reverse the effects of the labile endogenous inhibitor from peritoneal dialysate was consistently lower than that for ouabain, which is compatible with either greater potency of the labile factor in VSM or greater affinity for Digibind. These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume-sensitive hypertension of renal disease.
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PMID:Reversal of sodium pump inhibitor induced vascular smooth muscle contraction with digibind. Stoichiometry and its implications. 883 5

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.
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PMID:The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. 918 84

Increased levels of hemostatic factors and genetic mutations of proteins involved in coagulation may play a role in the pathogenesis of coronary artery disease. We investigated clotting activity of factors II (FII:C), V (FV:C), VII (FVII:C), and X (FX:C), the prothrombin gene 20210G-->A transition, and the factor V Leiden mutation in 200 survivors of myocardial infarction and in 100 healthy controls. FV:C (P<0.0001) and FVII:C (P<0.0001) were found to be independent risk factors for myocardial infarction. High FV:C or high FVII:C combined with smoking or arterial hypertension increased the relative risk for myocardial infarction up to 50-fold. One of 177 patients (0.6%) and 4 of 89 controls (4.5%) had the prothrombin 20210 AG genotype. Eleven of 177 patients (6.2%) and 6 of 89 controls (6.7%) were heterozygous for the factor V Leiden mutation. No homozygous carrier for these mutations was found. Neither the prothrombin gene 20210G-->A transition (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01 to 1.1) nor the factor V Leiden mutation (OR, 1.0; 95% CI, 0.4 to 2.8) were associated with an increased relative risk for myocardial infarction. In conclusion, our data indicate that neither the prothrombin gene 20210G-->A transition nor the factor V Leiden mutation are risk factors for myocardial infarction. High FVII:C was confirmed to be an independent risk factor for myocardial infarction. Moreover, we describe for the first time that high FV:C is an independent risk factor for myocardial infarction.
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PMID:Coagulation factors II, V, VII, and X, prothrombin gene 20210G-->A transition, and factor V Leiden in coronary artery disease: high factor V clotting activity is an independent risk factor for myocardial infarction. 1019 31

Estrogen replacement therapy (ERT), which produces acquired resistance to activated protein C when superimposed on heritable resistance to activated protein C (the mutant Factor V Leiden trait), may promote venous and arterial thrombosis. In a cross-sectional study of 423 women referred for hyperlipidemic therapy (93 of whom [22%] were on ERT), our specific aim was to determine whether ERT and heterozygosity for the Factor V Leiden mutation and/or resistance to activated protein C interacted as risk factors for atherothrombosis. Of the 423 women, 168 (40%) had atherothrombosis, 19 (4%) were heterozygous for Factor V Leiden mutation or had resistance to activated protein C <2 (Factor V Leiden mutation+), and 404 were wild-type normal for the Factor V gene and/or had resistance to activated protein C > or =2 (Factor V Leiden mutation-). By stepwise logistic regression, positive explanatory variables for atherothrombosis included hypertension (p = 0.002), age (p = 0.003), relatives with atherothrombosis (p = 0.002), anticardiolipin antibody immunoglobulin-M (p = 0.02), and a Factor V Leiden mutation*ERT interaction term where atherothrombosis events were more likely in 2 subgroups of women (ERT- and Factor V Leiden mutation-) or (ERT+ and Factor V Leiden mutation+) (p = 0.02). High-density lipoprotein cholesterol was inversely associated with atherothrombosis (p = 0.004). In a separate logistic regression model for the 213 women with a polymerase chain reaction measurement of the Factor V gene, ERT was protective (p = 0.008); the Factor V Leiden mutation was positively associated with atherothrombosis (p = 0.05). The atherothrombosis odds ratio risk for ERT (yes vs no) was 0.36 (95% confidence intervals [CI] 0.16 to 0.74, p = 0.007). The atherothrombosis risk odds ratio in women heterozygous for the Factor V Leiden mutation (vs normal) was 2.00 (95% CI 1.02 to 4.22, p = 0.05). ERT may be protective against atherothrombosis when the Factor V Leiden mutation is absent, whereas the Factor V Leiden mutation may increase risk for atherothrombosis, particularly in the presence of ERT. We suggest that the Factor V Leiden mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the Factor V Leiden mutation (4%), in whom ERT is relatively or absolutely contraindicated because of increased risk for atherothrombosis and thromboembolism. A second, much larger group of women will also be identified without the factor V Leiden mutation (96%), in whom ERT may reduce the risk for atherothrombosis.
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PMID:Effect of exogenous estrogen on atherothrombotic vascular disease risk related to the presence or absence of the factor V Leiden mutation (resistance to activated protein C). 1048 53

A common mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C (APC). Recent studies have shown that the prevalence of APC resistance is associated with severe pregnancy-induced hypertension (PIH). Our objective was to determine whether the factor V Leiden mutation is more prevalent in patients who developed severe PIH than in normotensive pregnant women. In 70 women with a history of severe PIH, of whom 15 had pre-eclampsia, we investigated common coagulation factors as well as APC resistance (factor V related). We found that seven of these 70 women showed low values for APC. Out of these, five were heterozygous and none was homozygous for factor V Leiden mutation. In a control group of normotensive pregnant women we found a 3.0% rate of APC resistance and a 3.0% rate of carriers of the Leiden mutation. These results indicate a significantly higher prevalence of both APC resistance and factor V Leiden mutation in women with severe PIH. Placental infarctions and micro-embolisms are considered to be one of the principle pathophysiological changes in severe PIH. Our results suggest that APC resistance is a risk factor for severe PIH, in addition to its well-known role in macrothrombo-embolism.
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PMID:Activated protein C resistance shows an association with pregnancy-induced hypertension. 1060 Nov 5

Recent studies in Caucasian populations have shown an association of the Leiden mutation in factor V with preeclampsia (PE). It consists of a substitution of a G (G1691) with an A (A1691) at nucleotide position 1691 in exon 10, resulting in arginine instead of glutamine at residue 506 at the factor V cleavage site for activated protein C (APC); it contributes to the resistance to APC. The purpose of this study was to determine whether the Leiden mutation is associated with pregnancy-induced hypertension (PIH), including PE, in Japanese women. We examined the genotypes of factor V of 71 Japanese patients with PIH and 109 controls. None of the 180 Japanese women carried the factor V Leiden mutation. To date, the factor V Leiden mutation is rare and not a common cause of PIH in Japan. The results may suggest that there is a significant ethnic difference in the role of the Leiden mutation in compounding the risk factors in the pathogenesis of PIH between Japanese and Caucasian populations.
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PMID:The factor V Leiden mutation is not a common cause of pregnancy-induced hypertension in Japan. 1062 7

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.
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PMID:Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study. 1066 53

Recent studies of current oral contraceptives indicate that the risk of cardiovascular sequelae is low in young (age 20-24 years) reproductive-aged women. Venous thromboembolism remains the one event that occurs in users independent of the presence of risk factors. However, the attributable risk is small, in the range of 7 to 18 events per 100,000 women annually. This risk is proportional to estrogen dose until the level of 30-35 microg is reached; type of progestin may also influence risk, though recent studies are controversial. Modifiable risk factors for venous thromboembolism include the presence of hemostatic disorders, especially factor V Leiden, and perhaps obesity. Stroke is even more uncommon, with an attributable risk of about 1.5 events per 100,000 women annually. Cigarette smoking and hypertension are modifiable risk factors for both ischemic and hemorrhagic stroke; use of preparations with 50 microg of estrogen or higher and migraine headaches are risk factors for ischemic stroke. Eliminating risk factors among users substantially reduces the risk of ischemic stroke and virtually eliminates the risk of hemorrhagic stroke. Myocardial infarction is rare among young women, occurring at a rate of about 0.2 event per 100,000 women annually. Oral contraceptive users who are non-smoking and normotensive do not have an increased risk of myocardial infarction. However, the presence of these risk factors along with age acts synergistically to increase the risk among oral contraceptive users.
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PMID:Cardiovascular issues with oral contraceptives: evidenced-based medicine. 1083 Nov 86

Central retinal vein occlusion is one of the most common retinal vascular disorders. Few and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion. The aim of this study was to investigate the most common hemostasis-related inherited risk factors for venous thrombosis in a group of 53 central retinal vein occlusion patients (median age 59 years, range 18-77 years) and in 53 comparable control subjects (median age 57 years, range 22-84 years). No difference was found in antithrombin III, protein C and protein S plasma levels between patients and controls. At univariate analysis, activated protein C resistance (odds ratio 5.8) and factor V Leiden (odds ratio 4.4) were significantly associated with central retinal vein occlusion whereas G20210A polymorphism of the prothrombin gene was not. After adjustment for sex, age, and the other classic vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking) activated protein C resistance remained the only independent risk factor for central retinal vein occlusion (odds ratio 11.5). These data indicate that activated protein C resistance may play a role in the pathophysiology of central retinal vein occlusion.
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PMID:Activated protein C resistance is a risk factor for central retinal vein occlusion. 1105 59

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.
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PMID:Clotting disorders and placental abruption: homocysteine--a new risk factor. 1130 Nov 73


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