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)

Moderate hyperhomocysteinaemia is a frequent finding in atherothrombotic cerebrovascular disease. This study confirms and extends this observation. Hyperhomocysteinaemia was present in 57 of 142 survivors with stroke (40%) and in four of 66 controls (6%). Plasma homocysteine concentrations were increased not only in carotid artery disease or lucunar stroke but also in haemorrhagic or embolic strokes. Homocysteine values were unrelated to the presence of hypertension, smoking, or hypercholesterolaemia, or to the concentrations of blood glucose, glycosylated haemoglobin, and plasma fibrinogen. Multiple regression analysis of the patient data showed that about 40% of the variation in plasma homocysteine concentrations could be predicted by the values for the homocysteine metabolism cofactors, blood folate and plasma pyridoxal 5-phosphate and by renal function as reflected in the values for serum creatinine. In patients, urine excretion of homocysteine per unit creatinine was significantly increased and strongly correlated both to the plasma homocysteine concentration and to the values for blood folate, plasma pyridoxal 5-phosphate, and serum vitamin B12. We conclude that moderate hyperhomocysteinaemia is frequently present in cases of stroke, is independent of other stroke risk factors or the type of stroke, and is partly related to renal function and the concentrations of homocysteine metabolism cofactors.
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PMID:Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. 158 47

The objective of this study was to examine if hyperhomocysteinemia is associated with occlusive vascular disease in hemodialysis patients. The study design included risk factor analysis and determination of serum homocysteine in hemodialysis patients. Fifty chronic uremic patients on regular hemodialysis treatment were studied. Twenty-four patients had coronary, cerebral, or peripheral signs of occlusive vascular disease. Cerebral vascular disease was diagnosed by computed tomography, arterial angiography, or Doppler sonography of the carotid and vertebral arteries. Coronary vascular disease was diagnosed by documented history of myocardial infarction or by coronary angiography. The diagnosis of peripheral vascular disease was established by angiography of the lower limb arteries. In all control patients, Doppler sonography of the carotid, vertebral, and lower limb arteries and thallium-201 exercise imaging were without pathologic results. Measurements included blood pressure, body mass index, smoking behavior, serum homocysteine (measured by gas chromatography/mass spectrometry), serum total, low-density lipoprotein, and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides, and plasma fibrinogen. In a stepwise multiple logistic regression analysis, high serum homocysteine was significantly associated with occlusive arterial disease (R = 0.23; P = 0.031). Furthermore, hypertension (R = 0.18; P = 0.058), but not serum total, low-density lipoprotein, and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides, diabetes mellitus, body mass index, plasma fibrinogen, and smoking behavior, was significantly associated with atherosclerosis. Our results support the hypothesis that hyperhomocysteinemia is an independent risk factor for vascular disease in hemodialysis patients.
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PMID:Hyperhomocysteinemia and the risk for vascular disease in hemodialysis patients. 757 64

Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40-59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/-, 54%; -/-, 35% (+ and-indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p < 0.05). Therefore, we concluded that there was no significant relationship between the MTHFR gene mutation and hypertensive subjects studied in this study.
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PMID:A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population. 877 90

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.
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PMID:Hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess in maintenance dialysis patients: a matched case-control study. 883 31

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

In homozygous homocystinuria due to cystathionine synthase deficiency, characterized by severe hyperhomocysteinemia, there is a high incidence of vascular complications. These observations focus on homocysteine as an atherogenic and thrombophilic agent. At the present time, there is also convincing evidence that even mild hyperhomocysteinemia is a risk factor for cardiovascular disease due to occlusive arterial complications. Furthermore, a positive association between mild hyperhomocysteinemia and the occurrence of venous thrombosis has been shown but needs further study. Mildly elevated homocysteine levels affect the arterial system independently from conventional risk factors. This newly- recognized factor seems equally strong in risk to hypercholesterolemia and smoking, while hypertension leads to a larger excess risk. It interacts synergistically with hypertension and smoking in a joint arteriosclerotic effect in patients with the concomitant presence of these risk factors. The homocysteine-lowering efficacy of a simple and safe vitamin regimen has been proven but data on the clinical outcome of such intervention are lacking thus far.
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PMID:Hyperhomocysteinemia as a risk factor for arterial and venous disease. A review of evidence and relevance. 919 7

The high incidence of vascular complications in severe hyperhomocysteinaemia in homozygotes for cystathionine beta-synthase deficiency has focused attention upon homocysteine as an atherogenic and thrombophilic agent. For two decades there has been accumulating evidence of mild hyperhomocysteinaemia as risk factor of vascular disease. Pooled data on hundreds of coronary, cerebrovascular and peripheral arterial disease patients show that mild hyperhomocysteinaemia was detectable in about 20-30%. In a recent meta-analysis of 27 studies up to 1994, including about 4000 patients and as many controls, it is calculated that the summary odds ratio of elevated homocysteine levels was 1.7, with 95% confidence interval (CI) 1.5-1.9, for coronary heart disease; it was 2.5, with 95% CI 2.0-3.0, for cerebro-vascular disease; and it was 6.8, with 95% CI 2.9-15.8, for peripheral vascular disease. The relevance of this newly recognized risk factor will be demonstrated by the outcome of the European Comac study on 'Hyperhomocysteinaemia and Vascular Disease', a multicentre case-control study on 800 vascular patients and 750 controls. Despite the selection for epidemiological reasons of a relatively low cut-off level as the criterion for mild hyperhomocysteinaemia in this study-the upper 20% of the distribution of control levels-the relative risk of thus-defined hyperhomocysteinaemia for arterial disease is about 2. This equals the relative risk of hypercholesterolaemia and of smoking; hypertension leads to a higher excess risk. The observed synergistic interaction between hyperhomocysteinaemia and hypertension and smoking may warrant a change in the now generally followed procedure of screening for hyperhomocysteinaemia only if conventional risk factors have not been detected in the patient. Those vascular patients with combined risk factors leading to synergism in their joint effect may profit most from homocysteinelowering intervention.
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PMID:The case for mild hyperhomocysteinaemia as a risk factor. 921 Dec 2

Cardiomyopathy in chronic uremia results from pressure and volume overload. The former causes concentric left ventricular [LV] hypertrophy, results from hypertension and aortic stenosis, and is also associated with diabetes mellitus and anemia. Volume overload causes LV dilatation, results from arteriovenous shunting, salt and water overload, and anemia, and is also associated with ischemic heart disease, hypertension, and hypoalbuminemia. Decreased major arterial compliance and an early return of arterial wave reflections are also associated with the extent of LV hypertrophy. Cardiomyopathy predisposes to diastolic and systolic dysfunction. The latter results from myocyte death, and predisposing factors include ischemic heart disease and the uremic environment. Ischemic heart disease may be atherosclerotic or nonatherosclerotic in origin. Multiple factors contribute to the vascular pathology of chronic uremia, including injury to the vessel wall, dyslipidemia, prothrombotic factors, increased oxidant stress, and hyperhomocysteinemia. Ischemic risk factors include hypertension, LV hypertrophy, hypoalbuminemia, and perhaps hyperparathyroidism. The clinical consequences of cardiomyopathy include heart failure, ischemic heart disease, dialysis hypotension, and arrhythmias. The adverse impact of ischemic heart disease is probably mediated through the development of cardiac failure.
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PMID:Cardiac disease in chronic uremia: pathogenesis. 923 25

Homocysteine is a graded risk factor for the incidence of stroke and for the degree of carotid atherosclerosis. Homocysteine is also a graded risk factor for the incidence of myocardial infarction but we do not know its precise relations to the severity of atherosclerosis in coronary patients. Seventy five symptomatic coronary patients were recruited for the study. Fifty of these patients had coronary artery disease only and were compared in a case-control manner to 50 healthy controls matched for age and sex. The 25 other coronary patients had also symptoms in another atherosclerotic territory (cerebral, peripheral or both) and were also compared to 25 matched controls. Mean plasma homocysteine level was significantly higher in coronary patients than in controls (11.7 +/- 0.7 mumol l-1, n = 50 versus 9.9 +/- 0.5 mumol l-1, n = 50, p < 0.05). Homocysteine in patients with symptomatic atherosclerosis in two or three arterial sites was 15.7 +/- 1.5 mumol l-1 which differed significantly from matched controls and from patients with coronary artery disease only (p = 0.01). The extent of coronary atherosclerosis evaluated by an angiographic coronary score correlated weakly to plasma homocysteine levels (r = 0.25, p < 0.05). The patients with both hypertension and high levels of homocysteine (> 11.3 mumol l-1, median value) had more severe coronary atherosclerosis (coronary score of 16.3 +/- 2.3 versus 11.9 +/- 0.9, p < 0.05) and more diffuse atherosclerosis (number of atherosclerotic territories of 1.5 +/- 0.2 versus 1.2 +/- 0.7, p = 0.08) than the coronary patients without this association. There were no other high risk association when considering the other classical risk factors. Thus, the highest levels of homocysteine were present in patients with coronary disease and another symptomatic localisation of atherosclerosis. A small gradient in the extent of coronary atherosclerosis was found with increasing levels of homocysteine. The presence of both hypertension and hyperhomocysteinemia was associated with more severe coronary atherosclerosis.
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PMID:Plasma homocysteine and the extent of atherosclerosis in patients with coronary artery disease. 926 41

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.
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PMID:Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients. A prospective study. 940 27


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