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)

Mild hyperhomocysteinemia, a putative risk factor for atherothrombotic cardiovascular disease morbidity and mortality, may contribute to the excess incidence of atherothrombotic outcomes in the dialysis-dependent end-stage renal disease population. Hemodialysis access (fistula or graft) thrombosis is an unfortunately common and costly morbidity in this patient population. In this study, using a prospective design, the potential relationship between baseline nonfasting, predialysis plasma total homocysteine (tHcy) levels and vascular access-related morbidity was examined in a cohort of 84 hemodialysis patients with a fistula or prosthetic graft as their primary hemodialysis access. Vascular access thrombotic episodes were recorded over a subsequent 18-mo follow-up period. Forty-seven patients (56% of the total) had at least one access thrombosis during the 18-mo follow-up period (median follow-up, 13 mo; rate, 0.6 events per patient-year of follow-up). Proportional hazards modeling revealed that each 1 microM/L increase in the tHcy level was associated with a 4.0% increase in the risk of access thrombosis (95% confidence interval, 1.0 to 6.0%, P = 0.008). This association persisted after adjustment for type of access (fistula versus graft), age, gender, time on dialysis, diabetes, smoking, hypertension, nutritional status, urea reduction ratio, dyslipidemia, and the presence of previous vascular disease. Elevated tHcy levels appear to confer a graded, independent increased risk for hemodialysis access thrombosis. A randomized, controlled trial examining the effect of tHcy-lowering intervention on hemodialysis access thrombosis appears to be justified.
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PMID:Plasma total homocysteine and hemodialysis access thrombosis: a prospective study. 1023 97

The balance of evidence from observational studies suggests that elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke. There is however a paucity of prospective studies. There are also concerns regarding confounding due to factors associated with hyperhomocysteinemia, including renal impairment, an atherogenic diet and cigarette smoking. Homozygosity for a defective thermolabile variant of MTHFR, a common genetic polymorphism which results in hyperhomocysteinemia, has not been consistently linked with stroke or other vascular disease. There is a need for additional prospective studies with data on relevant confounders, sufficient power to characterise the form of the association between homocysteine concentrations and stroke risk, whether linear or threshold, and power to study interactions between homocysteine, other dietary markers and established stroke risk factors such as smoking and hypertension. Similarly, the evidence linking hyperhomocysteinemia with hypertension is limited and inconsistent. Given the biological mechanisms proposed in support of the homocysteine-CVD hypothesis, one would predict a positive association between homocysteine and blood pressure. There is a need to address this hypothesis directly in studies with reliable measurements of both homocysteine and blood pressure. Ultimately, the case for a causal role for elevated homocysteine levels in vascular disease, including hypertension and stroke, will depend on data from randomised controlled trials of homocysteine lowering interventions. Given the high prevalence of hyperhomocysteinemia in apparently well nourished populations and the tendency for homocysteine concentrations to increase with age, modest effects of homocysteine on stroke risk will have profound implications for public health.
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PMID:Homocysteine, hypertension and stroke. 1037 45

This study examined the relationship between homocysteine and its metabolites, and hypertension in a cohort of Sri Lankan patients with essential hypertension. Serum homocysteine, cysteine, cysteinylglycine and glutathione were measured in 86 patients with a diagnosis of essential hypertension and compared with those of an age- and sex-matched control group. Patients with hypertension had significantly higher mean serum concentrations of homocysteine, cysteine and cysteinylglycine. The odds ratio for hypertension for those with a mean serum homocysteine concentration above 18 mumol/l was 2.8. Hyperhomocysteinaemia is a risk factor for hypertension in Sri Lankans and can lead to a threefold increase in risk.
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PMID:Association between hyperhomocysteinaemia and hypertension in Sri Lankans. 1041 60

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusive vascular pathology. In the current study, we determined the prevalence of a newly described mutation in the human MTHFR gene A1298C, and the already known C677T mutation, and related them to plasma total homocysteine and folate concentrations. We studied 377 Jewish subjects, including 190 men and 186 women aged 56.8 +/- 13 y (range 32-95 y). The frequency of the homozygotes for the A1298C and the C677T MTHFR mutations was common in the Jewish Israeli population (0.34 and 0.37, respectively). Subjects homozygous (TT) for the C677T mutation had significantly greater plasma total homocysteine concentrations (P < 0.01) than subjects without the mutation (CC). Homozygotes (CC) for the A1298C mutation did not have elevated plasma total homocysteine concentrations. Our study indicated that subjects with the 677CC/1298CC genotype had significantly lower concentrations (P < 0. 05) than those with a 677CC/1298AA genotype. Neither mutation (the A1298C and the C677T) was associated with established cardiovascular risk factors such as hypertension, elevated total cholesterol or body mass index.
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PMID:A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. 1046 Feb

Hypertension is one of the most important risk factors for cardiovascular morbidity and mortality. Recently it has been suggested that the amino acid homocysteine contributes to this process. This study evaluates whether elevated plasma levels of homocysteine in hypertensive patients are associated with increased risk for cardiovascular events. Fifty hypertensive patients with a documented history of cerebral or cardiac events were age and gender matched to 50 hypertensive patients with no evidence of any cerebral or cardiac event. Demographic details, duration of hypertension, presence of other risk factors, and use of antihypertensive medications were recorded for each patient. Plasma levels of homocysteine were measured by high-performance liquid chromatography technology. The two groups had similar demographic parameters, with a mean age of 64.6 +/- 9.4 years. Patients with cardiovascular events were more likely to be past smokers and to have been treated with calcium antagonists, aspirin, and nitrates. Homocysteine levels were 12.1 +/- 5.8 micromol/L in those with documented cardiovascular disease and 11.1 +/- 4.7 micromol/L in those without (P = NS). Levels of plasma homocysteine were higher in those with hypercholesterolemia (P = .03) and in smokers, and tended to be lower in those who used beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics, and nitrates. Thus, hyperhomocysteinemia is not a feature of hypertensive patients with atherothrombotic events and there is no support for additive or synergistic effects between these two independent risk factors.
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PMID:Homocysteine levels in hypertensive patients with a history of cardiac or cerebral atherothrombotic events. 1048 Apr 68

Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with premature vascular disease. We tested the hypothesis that homocysteine is associated with vascular disease and other diabetic complications in patients with NIDDM. The current investigation is a cross-sectional analysis of baseline variables for participants in the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Men and women aged 40 to 74 years with NIDDM and a mean diastolic blood pressure (BP) of 80 mm Hg or higher were eligible. We measured serum levels of total homocysteine (tHcy), cystathionine, and methylmalonic acid (MMA) and correlated these values with clinical and other laboratory measures of the complications of diabetes mellitus in 452 subjects. tHcy was higher in males than in females and correlated with the duration of hypertension and systolic BP. tHcy was significantly correlated with MMA (r = .35, P < .0001) and cystathionine (r = .53, P < .0001) levels and inversely correlated with serum B12 (r = -.23, P < .0001) and folate (r = -.18, P < .0001). It was significantly correlated with serum creatinine (r = .28, P < .0001 for males and r = .39, P < .0001 for females) and inversely correlated with creatinine clearance (r = -.19, P < .005 for males and r = -.30, P < .0001 for females). tHcy was not increased in subjects with cardiovascular disease or retinopathy, but it was increased in those with neuropathy (10.3 v 9.3 micromol/L, P < .05) and macroalbuminuria (11.0 v 9.2 micromol/L, P < .005). Of these subjects, 2.2% met the criteria for vitamin B12 deficiency and 1% met the criteria for folate deficiency. We conclude that elevations of tHcy in this population appear to be the result of a combination of vitamin deficiency and decreased renal function and do not appear to be a predictor of cardiovascular disease.
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PMID:Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus. 1048 47

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.
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PMID:Nutrition and dietary supplements. 1051 85

Hyperhomocysteinemia has been associated with both vascular structure alterations and vascular clinical end points. To assess the relation between plasma homocysteine, structure and function of large arteries, and the presence of clinical vascular disease, we investigated a population of 236 hypertensive patients. We estimated arterial stiffness by measuring the carotid-femoral pulse wave velocity. Total plasma homocysteine was determined by fluorometric high-performance liquid chromatography. The presence of cardiovascular disease was defined on the basis of clinical events, including coronary heart disease, cerebrovascular disease, and peripheral vascular disease. In this population, pulse wave velocity was positively correlated with homocysteine, even after adjustments for age, mean blood pressure, extent of atherosclerosis, and creatinine clearance (P=0.016). Analysis of variance showed statistically significant differences between the mean values of homocysteine, creatinine clearance, and pulse wave velocity according to the extent of atherosclerosis, with an increase in these 3 parameters concomitant with an increase in the number of vascular sites involved with atherosclerosis. In conclusion, in hypertensive patients the levels of homocysteine are strongly and independently correlated to arterial stiffness measured by aortic pulse wave velocity. Plasma homocysteine, creatinine clearance, and aortic pulse wave velocity are higher in patients presenting with clinical vascular disease. These results suggest that the evaluation of aortic distensibility and homocysteine levels can help in cardiovascular risk assessment in hypertensive populations.
Hypertension 1999 Oct
PMID:Plasma homocysteine, aortic stiffness, and renal function in hypertensive patients. 1052 70

Norwegian renal transplant recipients have a high prevalence of cardiovascular disease. In this group of patients cardiovascular disease causes three out of four deaths. Well-known risk factors such as hypertension, dyslipidemia, impaired glucose tolerance and diabetes mellitus are common in renal transplant recipients, but these factors cannot fully explain the high cardiovascular morbidity and mortality. Atherosclerotic disease and left ventricular hypertrophy are highly prevalent in uremic patients before transplantation. Hyperhomocysteinemia, elevated levels of advanced glycosylated end products, and immunosuppressive medication may also accelerate the atherosclerotic process. Until results from controlled trials on the effect of lipid-lowering therapy in renal transplant recipients are available, treatment decisions must be based on studies in non-transplanted patients. Every patient should be treated individually with the overall risk pattern taken into account.
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PMID:[Cardiovascular disease after kidney transplantation]. 1057 45

Oxidative stress has been implicated as an important etiologic factor in atherosclerosis and vascular dysfunction. Antioxidants may inhibit atherogenesis and improve vascular function by two different mechanisms. First, lipid-soluble antioxidants present in low-density lipoprotein (LDL), including alpha-tocopherol, and water-soluble antioxidants present in the extracellular fluid of the arterial wall, including ascorbic acid (vitamin C), inhibit LDL oxidation through an LDL-specific antioxidant action. Second, antioxidants present in the cells of the vascular wall decrease cellular production and release of reactive oxygen species (ROS), inhibit endothelial activation (i.e., expression of adhesion molecules and monocyte chemoattractants), and improve the biologic activity of endothelium-derived nitric oxide (EDNO) through a cell- or tissue-specific antioxidant action. alpha-Tocopherol and a number of thiol antioxidants have been shown to decrease adhesion molecule expression and monocyte-endothelial interactions. Vitamin C has been demonstrated to potentiate EDNO activity and normalize vascular function in patients with coronary artery disease and associated risk factors, including hypercholesterolemia, hyperhomocysteinemia, hypertension, diabetes, and smoking.
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PMID:On the role of vitamin C and other antioxidants in atherogenesis and vascular dysfunction. 1060 78


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