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Query: UMLS:C0020538 (hypertension)
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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

Early onset vascular disease unexplained until today by usual risk factors (hyperlipidemia, hypertension, tobacco, stress), can now find an explanation in sulfur amino acid metabolism defect. By transsulfuration, alimentary methionine leads to homocysteine, which is itself turn into cysteine, or remethylated into methionine. Several abnormalities of these different pathways lead to plasma accumulation of homocysteine, which will be responsible of arterial or venous occlusive lesions, concerning peripheral or deep vessels. Homocysteine stays in plasma upon several forms: 75% being linked by disulfide bounds to proteins, 22% as disulfide, homocystine (homocysteine-homocysteine) or mixed-disulfide (homocysteine-cysteine), and less than 3% as free reduced homocysteine. Plasma reduction allows total homocysteine evaluation with amino acid autoanalyzer. The basal plasma homocysteine level is less than 14 microMl. However, levels near this basal value can be found in patients with latent abnormality, which needs to be revealed by a methionine loading test. This study concerns two methodologies and their application to the exploration of a patient with unidentified neurologic disorders. The first one describes a new galenic oral form of methionine. Other authors use the methionine load of 100 mg/kg dissolving it in a fruit juice glass. In order to obtain a complete dissolution of this weakly soluble substance and to ensure its total absorbtion by the patient, we prepare a granular form aimed to give in water a perfect flavoured suspension. The second methodology concerns methionine loading test and amino acid analysis. After 10 hours fasting, a 100 mg/kg peroral methionine load is realized performing 5 EDTA blood samples before and 4, 8, 12 and 24 hours after loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The homocysteinemia vascular risk factor. Methodologies and application to a clinical case]. 179 72

Homocysteine is an intermediate amino acid formed during the metabolism of methionine, a sulfur-containing essential amino acid, and cleared by the kidneys. The two major acquired causes of increased homocysteine values are chronic renal failure and absolute or relative deficiencies of folate, vitamin B12 or vitamin B6, three vitamins involved in the normal metabolism of methionine. We studied 176 patients (97 men and 79 women with mean age 56.3 +/- 14.8 years) with end-stage renal disease on peritoneal or hemodialysis. Homocysteine concentrations averaged 26.6 +/- 1.5 mumol/liter in patients with renal failure as compared to 10.1 +/- 1.7 mumol/liter in normals. Abnormal values exceeded the 95th percentile for normal controls in 149 patients, giving an overall prevalence of homocysteinemia of 85%. There was preservation of the negative correlation between homocysteine and folate (r = -0.48), suggesting responsiveness in spite of impairment. Increased homocysteine concentrations were associated with an increased odds ration for atherosclerotic and thrombotic complications independent of other traditional risk factors and the length of time on dialysis. The odds ratio for vascular events with homocysteine levels was 2.9 (CI 1.4 to 5.8) for the upper two quintiles of homocysteine values compared to the lower three quintiles adjusted for age, gender, hypertension, diabetes, hypercholesterolemia, smoking and time on dialysis. These data indicate that plasma homocysteine values represent an independent risk factor for vascular events in patients on peritoneal and hemodialysis. The mechanism by which high homocysteine concentrations might cause vascular damage in patients with renal failure remains unclear.
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PMID:Homocysteinemia and vascular disease in end-stage renal disease. 894 16

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

Homocysteine (Hcy) represents a branching point between the transsulfuration and transmethylation pathway of methionine. A large increase of plasma concentration of Hcy is observed in patients with inherited hyperhomocysteinemia. A moderated increase (above 10 microM) is also observed in various pathological conditions, such as arterial occlusion, hypertension, hyperlipidemia and chronic renal failure. While amino acids were largely studied using capillary electrophoresis with UV or laser-induced fluorescence detection (LIF), thiol-amino acids were not. In this work we present a new approach for testing homocysteine in human plasma using CE-LIF and fluorescein isothiocyanate. The low fluorescence yield of the fluorescein thiocarbamyl (FTC) thiol-amino acids limits, probably, the sensitivity of the detection to 8 x 10(-10) M (instead of 10(-12) M for FTC-arginine).
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PMID:Quantitation of homocysteine in human plasma by capillary electrophoresis and laser-induced fluorescence detection. 976 92

Fasting hyperhomocysteinemia is an independent risk factor for coronary artery disease, stroke, peripheral vascular atherosclerosis, and for arterial and venous thromboembolism. The risk for cardiovascular disease with homocysteine is similar to conventional risk factors. The interaction of hyperhomocysteinemia with hypertension and smoking is strong and the combined effect is more than multiplicative. The combined effect of homocysteine and cholesterol is additive. Homocysteine produces atherosclerosis, thromboembolism, and vascular endothelial cell injury. Vascular dysfunction produced by homocysteine may be due to endothelial cell damage. Homocysteinemia-induced atherosclerosis is probably due to various factors including endothelial cell injury, inability to sustain S-nitroso-homocysteine formation because of imbalance between production of nitric oxide by dysfunctional endothelium and homocysteine, smooth muscle cell proliferation, and thromboembolism. There is strong evidence that endothelial cell injury is associated with oxidative stress produced by homocysteine. Hyperhomocysteinemia is associated with numerous conditions, including coronary disease, stroke, peripheral vascular disease (carotid artery and cerebrovascular atherosclerosis), venous thrombosis, renal disease, diabetes mellitus, and organ transplant. Folic acid, vitamin B12 and B6 have been shown to be beneficial in reducing plasma homocysteine levels. Folic acid is specifically very effective, safe and inexpensive.
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PMID:Homocysteine, a Risk Factor for Cardiovascular Disease. 982 15

Recent developments in ultrasound technology enable the noninvasive measurement of structural and functional vessel wall changes. Until now, the effect of homocysteine on the arterial wall has remained unclear: reports on intima-media thickness (IMT) yield conflicting results, whereas data on vessel wall stiffness are lacking. Because several cardiovascular risk factors result in an increased IMT or stiffness, different groups at risk for atherosclerotic disease, with special emphasis on hyperhomocysteinemia, were studied. Nineteen patients homozygous and 14 subjects heterozygous for cystathionine beta-synthase (CBS) deficiency, 21 patients with familial hypercholesterolemia (FH), 15 patients with essential hypertension, 20 smokers, and 28 control subjects were studied. The IMT values (both right and left) of the common carotid artery (CCA), bulb (BUL), internal carotid artery (ICA), and common femoral artery (CFA) were measured in millimeters by high-resolution ultrasound (Biosound). The distensibility (DC, in 10(-3). kPa-1) and compliance (CC in mm2. kPa-1) coefficients of the CCA (right and left) and CFA (right) were determined by a wall track system (Pie Medical). The mean IMT of the posterior wall in the CCA was 0.70+/-0.09 mm in healthy controls. For patients with vascular disease, FH, and hypertension and in smokers, the mean CCA IMT was larger, whereas no major differences in IMT were observed in patients either homozygous or heterozygous for CBS deficiency. The DC and CC in the right CCA were 23.5+/-6.9 (10(-3). kPa-1) and 0.9+/-0.3 (mm2. kPa-1) in healthy subjects, slightly lower in patients homozygous for CBS deficiency, and clearly lower in patients with vascular disease, FH, and hypertension. No positive correlation was found between plasma homocysteine level and either IMT, CC, or DC. Because smoking was a confounder in each risk group, a stepwise regression analysis was carried out to assess the contribution of each risk factor on IMT and arterial wall stiffness. Age explained most of the variation in IMT of the CCA (coefficient of determination R2 of 0.34), whereas R2 values for serum low density lipoprotein cholesterol, smoking (pack-years), and systolic blood pressure were 0.08, 0.07, and 0.06, respectively. Homocysteine did not contribute to variation in IMT in both the CCA and CFA. Age and smoking contributed to the variation in IMT in the CFA. The variation in DC and CC in the right CCA and right CFA could in part be explained by age, low density lipoprotein cholesterol, and blood pressure. Plasma homocysteine concentration explained only a small proportion of the variation in DC in the CCA (R2=0.02) and in CC in the CFA (R2=0.04). In this study, no relationship was found between homocysteine level and the thickness of the arterial wall, with only a marginal influence on stiffness.
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PMID:Carotid and femoral artery wall thickness and stiffness in patients at risk for cardiovascular disease, with special emphasis on hyperhomocysteinemia. 984 90

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

Homocysteine is a sulphur-containing amino acid formed during metabolism by one of two pathways by remethylation and transsulfuration. Altered homocysteine metabolism may be implicated as a factor in atherosclerosis, cerebrovascular disease or peripheral vascular disease. It is postulated that homocysteine may damage endothelial cells or acts as a direct causal factor in the thromboembolic process. Several studies have reported that there are a number of factors that may influence levels of homocysteine in humans. Serum homocysteine levels may be associated with low levels of folate, vitamin B6 and vitamin B12. These studies showed that serum homocysteine levels were higher in men and older adults, and some showed that there was a direct relationship between homocysteine and cigarette smoking, diabetes, obesity, and hypertension. Subjects who consume larger amounts of coffee were also noted to have higher serum homocysteine levels. Several cross-sectional, case-control, and cohort studies have linked homocysteinaemia with cardiovascular disease morbidity and mortality. In the Framingham Heart Study, the cohort study in Tromso, Norway, and the Atherosclerosis Risk in Communities (ARIC) Study, homocysteine levels were found to be higher in adults with asymptomatic or symptomatic coronary artery disease. In the British Regional Heart Study, homocysteine levels were found to be significantly higher in patients with stroke. Thus, there are suggestions that vitamin therapy and alteration of lifestyle habits such as cigarette smoking may lower homocysteine levels. There may be less coronary heart disease morbidity and mortality with lower homocysteine levels.
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PMID:Homocysteine and atherosclerotic disease: the epidemiologic evidence. 1056 72

Over the past few years, a substantial body of evidence has accumulated that indicates hyperhomocysteinemia as a significant risk factor for cardiovascular disease. Hyperhomocysteinemia arises from a lack of key enzymes or vitamins such as methylenetetrahydrofolate reductase, vitamin B6, and folate which are involved in homocysteine metabolism. Heavy coffee consumption is also known to elevate homocysteine levels. The adverse effects associated with hyperhomocysteinemia are extensive. It increases risk of myocardial infarction, cardiovascular-related morbidity and mortality, peripheral vascular disease, atherosclerosis, coronary heart disease, and cerebrovascular disease. Its seriousness as a risk factor has been equated to hypercholesterolemia and smoking, two leading causes for cardiovascular disease. It also has been shown to produce a multiplicative effect with these and other risk factors such as hypertension. Two major hypotheses have been proposed to explain how homocysteine induces its harmful effects. It can damage endothelial cells lining the vasculature, allowing plaque formation. Simultaneously, it interferes with the vasodilatory effect of endothelial derived nitric oxide. Also, homocysteine has been found to promote vascular smooth muscle cells hypertrophy. Both of these processes induce vessel occlusion. Maintaining a normal plasma level of homocysteine as a means to prevent cardiovascular disease appears promising. This is achieved through increased intake of folate and vitamin B6 through diet or supplementation. Despite the overwhelming evidence suggesting homocysteine as a significant risk factor, no long-term prospective studies have been completed to demonstrate that folate and vitamin B6 can prevent cardiovascular disease related morbidity and mortality in patients with hyperhomocysteinemia. Homocysteine is a key metabolite in amino acid synthesis. During the process of methylation, S-adenosylmethionine (Ado Met), derived from methionine, is converted to S-Adenosylhomocysteine (Figure 1). This product is quickly hydrolyzed to form homocysteine and adenosine. Homocysteine can undergo 1 of 3 reactions depending on the status of the organism. If cysteine levels are inadequate, homocysteine utilizes the coenzyme pyridoxal phosphate (vitamin B6) to condense with serine, forming the intermediate cystathionine. Subsequent reactions with cystathionine lead to the formation of cysteine. When methionine levels are low, homocysteine is remethylated in a reaction involving the coenzyme N5-methyltetrahydrofolate or betaine. Finally, when both amino acids are in adequate supply, homocysteine is cleaved by the enzyme homocysteine desulthydrase (cystathionase) to form a-ketobutyrate, ammonia, and H2S. Thus, homocysteine's physiological role is to assist in maintaining sulfur-amino acid homeostasis. Beyond these metabolic processes, homocysteine is beginning to be recognized as a significant risk factor for cardiovascular disease including atherosclerosis, coronary artery disease, cerebrovascular disease, and myocardial infarction.
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PMID:Hyperhomocysteinemia: an additional cardiovascular risk factor. 1063 97


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