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)

Hyperhomocysteinemia is associated with arterial hypertension and endothelial dysfunction in healthy humans. Placebo-controlled vitamin intervention studies cannot distinguish intrinsic actions of homocysteine (tHcy) and folate concentrations on the endothelium. The present two-period crossover study investigates the effects of tHcy lowering through oral folic acid on antioxidant status and resistance vessel reactivity in patients with established coronary artery disease (CAD). We investigated 27 male patients with angiographically documented multivessel CAD aged 50 (range 46-56) years. Resistance vessel reactivity was assessed by measurement of postischemic reactive hyperemia (RH) in the forearm using venous occlusion plethysmography at baseline, after 6 weeks of treatment with 5 mg of oral folic acid, and after a washout period of another 6 weeks. Plasma folate increased 3.49-fold with a mean tHcy reduction of 21.3%. Peak reactivity of resistance vessels improved significantly (18.97-23.60 ml/min(-1) per 100 ml; P = 0.01) with unchanged total antioxidant status (TAS; 0.912-0.944 microM; P = 0.4). This effect was limited to subjects (n = 14) with a tHcy reduction >2 microM (median reduction, 14.4-9.6 microM, P < 0.001). In the 13 subjects with a below-median reduction, tHcy remained unaltered (9.7-9.6 microM, P = 0.88) and TAS increased significantly (0.923-1.055 microM, P = 0.006), whereas RH peak flow was not affected (20.22-22.99 ml/min(-1) per 100 ml, P = 0.28). Homocysteine lowering >2 microM through folic acid supplementation improves resistance vessel reactivity in patients with CAD. Our data support the hypothesis that homocysteine lowering may have intrinsic vasoprotective effects largely independent of folate.
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PMID:Effects of folate treatment and homocysteine lowering on resistance vessel reactivity in atherosclerotic subjects. 1223 46

Studies suggest that homocysteine may elevate blood pressure and increase the risk of hypertension. The association of homocysteine with blood pressure and with the risk of hypertension was investigated using cross-sectional data from the Third National Health and Nutrition Examination Survey (1998-1994). Homocysteine had an independent positive association with blood pressure after adjusting for cardiovascular risk factors. A 1 standard deviation ( approximately 5 micro mol/liter) increase in homocysteine was associated with increases in diastolic and systolic blood pressure of 0.5 and 0.7 mmHg, respectively, in men and of 0.7 and 1.2 mmHg in women. Similarly, higher levels of homocysteine were associated with an increased risk of hypertension. In a comparison of the highest and lowest quintiles of homocysteine, women had a threefold increase in the risk of hypertension (95% confidence interval (CI): 1.7, 5.4), and men had a twofold increase (95% CI: 0.7, 5.1). In light of the homocysteine-blood pressure association, the association of homocysteine with prevalent cardiovascular disease was examined with and without adjusting for blood pressure. The results support a mediating role for blood pressure in women and suggest that the full effect of homocysteine on cardiovascular risk may be underestimated when blood pressure is adjusted.
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PMID:Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey, 1988-1994. 1248 Jun 55

The objective of this study was to determine the prognostic value of serum homocysteine levels in patients with coronary heart disease. Homocysteine was assayed in 76 coronary patients with a mean age of 59.2 years hospitalized for myocardial ischaemia or myocardial infarction. Percutaneous transluminal angioplasty was performed in 47 (70%) of these patients during this hospitalization. The mean follow-up for these patients was 22 months (range: 11 to 67 months). In these patients, serum homocysteine levels were not correlated with the usual risk factors of coronary heart disease (age, sex, treated hypercholesterolaemia, smoking, diabetes) except for hypertension. It was strongly correlated with serum creatinine (R = 0.61; p = 0.0001). Eleven patients presented a major event during follow-up (8 deaths, 1 nonfatal myocardial infarction, 1 cardiac transplantation) and 16 underwent a revascularization procedure. The blood homocysteine level does not have any prognostic value for any coronary events. However, it is higher in patients who develop a major event than in those which do not (15.8 +/- 4 mumol/l versus 11.5 +/- 6.6 mumol/l, p = 0.05). Using multivariate analysis, taking into account age, serum creatinine and serum homocysteine, only serum homocysteine was predictive of major event-free survival (p = 0.02).
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PMID:[Homocysteine and coronary events in coronary disease patients]. 1255 79

Although white coat hypertension has been widely studied in the last years, its risk profile is not yet completely clear. The aim of this study was to evaluate circulating homocysteine levels, an emerging cardiovascular risk factor, in subjects with white coat and sustained hypertension. We selected 31 sustained hypertensive subjects, 31 white coat hypertensive subjects and 31 normotensive subjects matched for age, gender, body mass index and occupation. Women were also matched for menopausal status. Subjects with smoking habit, dyslipidaemia and diabetes mellitus were excluded from the study. White coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <135/85 mmHg. Blood samples were drawn after a fasting period of 12 h for routine laboratory tests and homocysteine determination. Homocysteine levels were evaluated by fluorescence polarization immunoassay. Creatinine, glucose, cholesterol and triglycerides were not different among the groups. White coat hypertensive subjects had significantly lower homocysteine levels than sustained hypertensive patients (8.2+/-2.0 vs 12.6+/-3.9 micromol/l, P=0.0003). No significant difference was observed between white coat hypertensive and normotensive subjects regarding this parameter (8.2+/-2.0 vs 7.6+/-1.9 micromol/l, P=0.9). In conclusion, our data show that middle-aged white coat hypertensive subjects without other cardiovascular risk factors have lower circulating homocysteine levels than sustained hypertensive patients suggesting that they are at lower cardiovascular risk.
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PMID:Circulating homocysteine levels in sustained and white coat hypertension. 1262 6

Homocysteine is a metabolic product of methyl group donation by the amino acid methionine. Moderate elevation of plasma homocysteine (>15 microM) is most commonly caused by B-vitamin deficiencies, especially folic acid, B(6) and B(12). Genetic factors, certain drugs and renal impairment may also contribute. Homocysteine has several potentially deleterious vascular actions. These include increased oxidant stress, impaired endothelial function, stimulation of mitogenesis, and induction of thrombosis. Homocysteine also appears to increase arterial pressure. In humans, experimental induction of hyperhomocysteinemia by methionine loading rapidly causes profound impairment of endothelium-dependent dilatation in both resistance and conduit arteries. This endothelial dysfunction can be reversed by administration of antioxidants. Epidemiological evidence suggests that homocysteine acts as an independent risk factor for atherosclerosis, thrombosis and hypertension. Prospective studies have shown that elevated plasma homocysteine concentrations in the top quintile of the population (>12 microM) increase risk of cardiovascular disease by about 2-fold. There are currently no data available from randomized, controlled trials of the effects of lowering plasma homocysteine on atherothrombotic events. Nonetheless, it would seem appropriate to screen for and treat hyperhomocysteinemia in individuals with progressive or unexplained atherosclerosis. Folic acid and vitamins B(6) and B(12) are the mainstay of therapy. Treatment of moderately elevated plasma homocysteine in patients without atherosclerosis should be deferred until the completion of randomized outcome trials.
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PMID:Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. 1265 8

The C677T transition of methylenetetrahydrofolate reductase (MTHFR) gene causes a moderate increase in total plasma homocysteine (tHcy). We studied the effect of MTHFR TT homozygosity and mild hyperhomocysteinemia on arterial hypertension. Normotensive controls (n = 223) and hypertensive subjects (n = 235) were matched for age, gender, and history of cardiovascular disease. Homocysteine levels were measured by a polarization immunoassay method. Methylenetetrahydrofolate reductase we determined by polymerase chain reaction and restriction fragment analysis. Hypertensives showed elevated tHcy compared to normotensive group in men (P = 0.039). Homocysteine values higher than 15 micromol/L were associated with increased hypertensive risk in the male population [odds ratios (OR) = 1.63; 95% confidence interval (CI) = 1.06-2.52; P = 0.027]. In multivariate analysis, TT genotype was associated with an increased risk of hypertension in males (OR = 2.27; 95% CI = 1.12-4.60; P = 0.022) An increased hypertensive risk was observed in those TT males with tHcy levels higher than 15 micromol/L (OR = 2.78; 95% CI = 1.05-7.3; P = 0.032) but not in those non-TT males with tHcy levels higher than 15 micromol/L (P = 0.33). Our findings do not support the possibility that mild hyperhomocysteinemia my solely account for the hypertensive risk associated to the TT genotype.
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PMID:The effect of methylenetetrahydrofolate reductase C677T common variant on hypertensive risk is not solely explained by increased plasma homocysteine values. 1279 95

Syndrome X, a cluster of several metabolic disorders that includes hyperinsulinemia, hypertriglyceridemia, and hypertension, is associated with severe vascular morbidity. Hyperhomocysteinemia is another risk factor for cardiovascular and cerebrovascular diseases, often exhibited by insulin-resistant patients. In the current study, we investigated the relationship between syndrome X and hyperhomocysteinemia in a rat model. Two groups of rats were fed either fructose-enriched diet or standard rat chow for 5 weeks. Systolic blood pressure (SBP), as well as fasting plasma insulin, triglycerides, total cholesterol, and total homocysteine levels, were determined at the beginning and at the end of the study. A complete metabolic syndrome was induced by the fructose-enriched diet, including hyperinsulinemia, hypertriglyceridemia, and hypertension. Homocysteine concentration was 72% higher after 5 weeks on the fructose diet (8.49 +/- 1.6 v 4.92 +/- 0.9 micromol/l, P<.01). Insulin, triglycerides, SBP, and homocysteine levels were insignificantly changed during 5 weeks on standard rat chow. Homocysteine was positively and significantly correlated with any original component of syndrome X (r=0.565, P=.014 with insulin, r=0.662, P=.001 with triglycerides, and r=0.774, P<.001 with SBP). The results of the present study indicate that hyperhomocysteinemia is an integral component of this rat model of syndrome X. It is thus highly likely that hyperhomocysteinemia is an integral component of the human syndrome X as well, and thereby contributes to the overall high vascular risk associated with this condition.
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PMID:Hyperhomocysteinemia as a component of syndrome X. 1462 12

Homocysteine levels have been determined with Chromatography on HPLC column, between the 20th and the 24th week of pregnancy, in women with analogous characteristics (a) normotensive, (b) with pregnancy-induced hypertension (PIH), low (LR), medium (MR), high risk (HR). The group they belonged to was confirmed after natural or caesarean delivery. All the patients were submitted to 24 hour blood pressure monitoring for the evaluation of further pressure risk parameters: mean arterial pressure (MAP), non dippers, percentages of pressure peaks. Homocysteine levels in normotensive pregnant women (5.8 +/- 1.7 microM) were low. Significant high levels of homocysteine were present proportionally to the risk degree of PIH. Higher levels of homocysteine statistically significant were present in non dippers of all groups (MR p < 0.05; HR p < 0.01). A direct correlation between plasmatic homocisteine levels and pressure profiles was found out in non dippers (r = 0.56, r = 0.55, r = 0.50 respectively) and in dippers (r = 0.7, r = 0.75, r = 0.60 respectively), and also between levels of homocysteine, MAP value, and pathological percentages of systolic and diastolic nocturnal peaks. In pregnant women presenting preeclampsia afterwards, high levels of homocysteine were not different from mean values present in high risk PIH pregnant women (13.3 +/- 1.9 vs. 16.4 +/- 1.7 microM). High levels of homocysteine early determined in the second trimester of PIH pregnancies seem to be associated to a pregnancy higher risk, coexisting with dangerous pressure profiles. High levels confirm a pregnant woman to belong to a higher or lower risk degree of vascular damage, but in the same group context high levels of homocisteine do not allow to identify those pregnant women who will develop eclampsia.
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PMID:Hyperhomocysteinemia in preeclampsia is associated to higher risk pressure profiles. 1465 Jun 44

About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and getting larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B12, and vitamin B6 deficiencies and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10% of total risk. Elevated plasma homocysteine levels (>12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10% of the general population and in up to 40% of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence over-proportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial anti-thrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stress. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and lifestyle factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine levels in high-risk individuals in general and patients with manifest vascular disease in particular. Subjects of both populations should first have a baseline homocysteine assay. Except where manifestations are already present, intervention, if any, should be guided by the severity of hyperhomocysteinemia. Consistent with other working parties and consensus groups, we recommend a target plasma homocysteine level of <10 micromol/l. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25% of cardiovascular events. Supplementation is inexpensive, potentially effective, and devoid of adverse effects and, therefore, has an exceptionally favorable benefit/risk ratio. The results of ongoing randomized controlled intervention trials must be available before screening for, and treatment of, hyperhomocysteinemia can be recommended for the apparently healthy general population.
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PMID:DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. 1465 16

Homocysteine is a sulphur aminoacid with a free thiol group which is not present in dietary protein. This aminoacid is a secondary f methionine by-product from cysteine metabolism. The pathogenic mechanisms of homocysteine in vascular damage have not been clarified. At present, it is no possible to develop an atherogenic and thrombogenic hypothesis. Yet high levels of homocysteine can cause endothelial damage, with increased thrombosis and atherosclerosis. Hyperhomocysteinemia has been reported in patients with diabetes mellitus type 1 and type 2; the prevalence and secondary cardiovascular risk is higher in patients with diabetes type 2 than those with diabetes type 1. In patients with diabetes mellitus type 1, microvascular and macrovascular complications and neuropathy are found to be increased in those with hyperhomocysteinemia. In patients with diabetes mellitus type 2, the relationship between hyperhomocysteinemia, macrovascular complications and renal disease is unclear; however, a higher prevalence of macrovascular complications in diabetic patients with hyperhomocisteinemia is associated with a higher prevalence of renal disease. Moreover, patients with hyperhomocysteinemia have hypertension and dyslipemia. Multivariate regression analyses have shown an independent relationship between homocysteine and macrovascular complications. The relationship between retinopathy and homocysteine has not been clarified. In summary, hyperhomocysteinemia could be a risk factor accounting for chronic complications in diabetic patients. Nevertheless, it is necesary to perform more prospective and intervention studies to clarify the independent risk of homocysteine and thus assay alternative treatments.
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PMID:[Homocysteine in patients with diabetes mellitus]. 1473 72


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