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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In only 50% of cases of coronary heart disease (CHD) is the cause attributable to the established risk factors of hypertension, cigarette smoking, and elevated total and low-density lipoprotein (LDL) cholesterol levels. This finding has led to research examining other markers for CHD that may have a causal link to the atherothrombotic process. Several of these "emerging" risk factors are reviewed in this article: lipoprotein(a); small dense LDL particle size; hyperhomocysteinemia; and inflammatory, infectious, and hemostatic factors. Evaluation of each of these factors includes a review of the epidemiologic evidence, examination of the pathologic mechanism(s) by which the factor might participate in atherothrombosis, and the clinical utility of screening. Finally, and most relevant for the practicing clinician, the following is addressed: Does evidence exist that selective modification of these risk factors is associated with net clinical benefit?
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PMID:Novel risk factors for coronary heart disease: emerging connections. 1065 79

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean +/- SEM, 8.1 +/- 0.6 v 6.8 +/- 0.2 micromol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 +/- 0.5 v 7.2 +/- 0.5 v 8.4 +/- 0.6 micromol/L; P = .148) or normotensive subjects (6.3 +/- 0.4 v 8.0 +/- 0.8 v 7.0 +/- 0.8 micromol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.
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PMID:Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects. 1067 66

Increasing age and male gender are unavoidable risk factors for peripheral arterial occlusive disease (PAOD). A number of studies have looked at classical risk factors for atherosclerosis, such as diabetes, hypertension, lipid abnormalities, and smoking, as well as some more recently identified associations, such as plasma fibrinogen levels, impaired glucose tolerance, and hyperhomocysteinemia. However, most "risk factors" are really associations. A causal relationship may only reasonably be firmly established if a prospective controlled study shows that removing the risk factor significantly alters the course of the disease, as with smoking. Smoking is probably the strongest risk factor for intermittent claudication (IC), but hyperhomocysteinemia also appears to be strongly associated with the development of PAOD. Moderate alcohol intake and regular physical exercise appear to have a protective effect. A genetic risk factor is suggested but not as yet confirmed. The magnitude of the association varies from odds ratios of 2 to 3 for smoking and diabetes. There is insufficient evidence for hyperhomocysteinemia, but the effect may be even greater. The association with hypertension and lipid abnormalities is surprisingly inconclusive.
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PMID:Predictors of early disease in the lower limbs. 1077 37

All uremic patients have multiple risk factors for CAD including in many, the conditions that caused their ESRD--for example, diabetes and hypertension. conventional risk factors--for example, dyslipidemia and hyperhomocysteinemia. risk factors that are unique to uremia--for example, calcium and phosphate abnormalities. PD patients have particular risk with respect to their lipid status and hyperinsulinemia. Many of these risks are potentially modifiable, but evidence does not exist to assess the impact of treatment on clinical outcomes. Therefore, current decisions for therapy directed at risk factor modification must be made on an individual basis.
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PMID:Major and minor risk factors for cardiovascular disease in peritoneal dialysis. 1091 62

Cardiovascular disease is the leading cause of death in patients receiving dialysis. This is attributed in part to the shared risk factors of cardiovascular disease and end-stage renal disease. The risk factors for coronary artery disease include the classic cardiac risk factors of diabetes mellitus, hypertension, dyslipidemia, and smoking. Also in this population, hyperparathyroidism, hypoalbuminemia, hyperhomocysteinemia, elevated levels of apolipoprotein (a), and the type of dialysis membrane may play a role. Management begins with risk factor modification and medical therapy including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and lipid-lowering agents. Revascularization is often important, and coronary artery bypass grafting appears to be preferable to percutaneous transluminal coronary angioplasty. This is especially true for those with multivessel disease, impaired left ventricular function, severe symptoms, or ischemia. Congestive heart failure is another common problem in dialysis patients. The management includes correction of underlying abnormalities, optimal dialysis, and medical therapy. Data obtained from the general population indicate obvious benefits from ACE inhibitors and beta blockers, and these agents would be considered the therapies of choice. Erythropoetin is also an essential component of therapy, but the ideal hemoglobin concentration has yet to be determined. Peritoneal dialysis may be helpful in severe cases of heart failure. Pericarditis is seen in less than 10% of dialysis patients and is best diagnosed by clinical examination and echocardiography. Intensive dialysis is often the best initial therapy. Pericardiocentesis is reserved for the setting of pericardial tamponade, but a pericardial window is more definitive.
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PMID:Cardiac complications of end-stage renal disease. 1092 9

Numerous studies report strong associations between hyperhomocysteinemia and premature atherosclerotic vascular disease. Causes of hyperhomocysteinemia are hereditary heterozygous or, in very rare cases, homozygous defects, and quite frequently a lack of the coenzymes B6 and B12 and the cosubstrate folate. Lifestyle factors, age, sex, acute and chronic illness, vitamin deficiency and certain drugs may elevate homocysteine concentrations. Vitamin B supplementation, especially folic acid, is an effective treatment of hyperhomocysteinemia. Clinical trials are required to confirm the potential benefit of lowering homocysteine in regard of the development and progression of atherosclerotic vascular disease. The relevance of hyperhomocysteinemia as a risk factor for atherosclerosis, in contrast to the classical triad of risk factors, namely hypercholesterolemia, smoking and hypertension, is still unknown. Furthermore, a lack of standardized analytical methods for the determination of both homocysteine and blood folate renders the evaluation of studies and clinical data difficult. Therefore, at present, diagnosis and treatment is only recommended in high-risk patients (strong family history of premature atherosclerosis or arterial occlusive disease, especially in the absence of other risk factors, as well as in members of their families) with hyperhomocysteinemia.
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PMID:Homocysteine--relevant for atherogenesis? 1095 70

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.
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PMID:Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. 1098 61

Atherosclerosis starts in childhood, and is accelerated in some individuals. A cluster of clinical and biochemical factors constitute the risk profile for many of them, perhaps most important being metabolic insulin resistance syndrome. Insulin resistance and its components for children and adolescents, especially obesity and dyslipidemia, are generators of hypertension, glucose intolerance and complications of atherosclerosis in adulthood. Some individuals are genetically predisposed, particularly those with the family history of such disorders. For many subjects, there is 'tracking' of metabolic and lifestyle factors from early age to adulthood. Several new risk factors of atherosclerosis (e.g. level of lipoprotein (a), procoagulant state, hyperhomocysteinemia, low birth weight and adverse in-utero environment, and possibly inflammatory markers) are current and potentially future areas of research concerning children and young individuals. Definition of and research on new and hitherto not investigated factors and formulation of strategies to neutralize the known factors are of paramount importance for primary prevention of atherosclerosis. Simple and effective measures for prevention include increasing awareness of the diseases, maintenance of ideal body weight, regular physical exercise, avoidance of smoking and chewing of tobacco, eating a balanced diet, and early periodic monitoring of blood pressure and metabolic status. These measures, starting from childhood, should be applied to all and in particular to the susceptible offspring, predisposed individuals, and populations.
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PMID:Risk factors for atherosclerosis in young individuals. 1100 92

Evidence of a positive association between mild hyperhomocysteinemia and arterial vascular disease has been accumulating in the last decade. Mild hyperhomocysteinemia acts as an independent vascular risk factor with equal strength as hypercholesterolemia and smoking. If jointly present with hypertension and smoking, its effect seems synergistic. This could make the outcome of homocysteine-lowering intervention beneficial, particularly in cases with concomitance of conventional vascular risk factors. So far, however, data on the clinical outcome of homocysteine-lowering treatment with a simple, safe, and cheap vitamin regimen are lacking. Trials investigating a beneficial clinical effect of homocysteine-lowering treatment using folic acid in a dose ranging from 0.2 to 5 mg daily, alone or in combination with vitamin B12 with or without vitamin B6 versus placebo, are ongoing. Furthermore, exploration of the unifying mechanism by which increased homocysteine levels may lead to both arterial and venous occlusions is warranted. These lines of investigations have to provide the ultimate proof of causality of hyperhomocysteinemia in vascular disease in the near future.
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PMID:Mild hyperhomocysteinemia is an independent risk factor of arterial vascular disease. 1101 46


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