Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contrary to the popular belief, coronary heart disease (CHD) is indeed common in the Indian sub-continent. Expatriate Indians in their newly adopted countries have 3 to 5 times more chance of developing CHD than the native population or the other immigrant groups. The well-known risk factors such as hypercholesterolemia, hypertension and smoking do not appear to play a major role, while the syndrome of insulin resistance seems to be an important risk factor for CHD in people of this sub-continent. Abdominal obesity, hypertriglyceridemia, and low plasma HDL cholesterol are the markers of this syndrome. Increased plasma insulin levels or even better, the C-peptide measurement may help in identifying the abnormality early. As CHD among Indians has been found to be severe and more diffuse with serious complications and increased mortality at a younger age, preventive measures need to be instituted early. Low fat and complex carbohydrate diet along with regular aerobic exercise may help reduce abdominal obesity, improve insulin sensitivity and HDL cholesterol levels. Hypertriglyceridemia uncontrolled by above measures may require pharmacotherapy with agents such as gemfibrozil. Smoking must be stopped to help reduce insulin resistance and improve HDL levels and endothelial function. Those with hypertension should be considered for therapy with ACE inhibitors, which may improve insulin sensitivity. In patients with insulin resistance, therapy with metformin or troglitazone may be helpful.
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PMID:Special features of coronary heart disease in people of the Indian sub-continent. 855 88

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact on cardiovascular disease, early detection and aggressive treatment is mandatory to ensure longlasting benefits for affected patients.
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PMID:[Arterial hypertension and metabolic syndrome]. 1468 1

With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest cause of mortality in diabetic patients. The concept that type 2 diabetes and CVD are linked via a common etiologic pathway (metabolic syndrome) has substantial ramifications for the care of individual patients. Many of the metabolic abnormalities that contribute to both glycemic disorders and CVD are interrelated. For example, hyperinsulinemia and insulin resistance coupled with abdominal obesity further worsens HTN and hyperlipidemia. Likewise, the procoagulant state and endothelial dysfunction increase with worsening glycemic control. Specific interventions include tobacco cessation, a food management and physical activity plan, choice of antidiabetic agent (such as metformin), and use of ACE inhibitors for hypertension and microalbuminuria (Table 5). Programs to enhance cardiovascular risk factor reduction as part of the comprehensive evaluation and management of diabetic patients have been described [95,99]. One community-based program provided free screening to diabetic patients with randomization to either annotated result reports provided to the patient and their physician or results provided by a project nurse (either face-to-face or over the phone). Greater improvements in mean glycohemoglobin, cholesterol, and blood pressure were noted with verbal presentation of results [99]. Recent data from the Centers for Disease Control and Prevention Diabetes Cost-effectiveness Group support the idea that interventions to decrease CVD in diabetics are economically beneficial. Intensive management of hypertension, glycemic control, and hyperlipidemia each improved health outcomes. Hypertension control reduced costs. Although intensive treatment of glucose and hyperlipidemia increased costs, the increase was comparable to that of other frequently used health care interventions [100]. Further directions include further exploration of the implications and management of metabolic syndrome as it relates to CVD prevention. Interventions such as exercise, which can impact on all outcomes, require special attention. Efforts by physicians, health systems, and society are necessary to increase physical activity for individuals of all ages. It makes clinical sense that the recommendations for prevention of CVD in diabetics described in this article may also benefit patients with prediabetes (fasting glucose 110-125 mg/dl), but this remains to be definitively shown.
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PMID:Preventing cardiovascular disease in diabetes and glucose intolerance: evidence and implications for care. 1469 2

About 60% of patients with mild and moderate hypertension have insulin resistance and half of them have clinically manifest metabolic syndrome which comprises abdominal obesity, hyperlipidemia, impaired glucose tolerance, hypertension and insulin resistance. In a framework of metabolic syndrome hypertension is characterized by disturbed circadian profile without nocturnal blood pressure lowering and concentric left ventricular hypertrophy. There exist 2 mechanisms of linkage between hypertension and metabolic syndrome: impaired ion transport and neurohormonal and humoral activation. Antihypertensive drugs for correction of hypertension in metabolic syndrome should be long acting, provide protection of target organs, and induce positive or neutral metabolic effect. Together with normalization of blood pressure these actions can cause lowering of risk of atherosclerosis development. Representatives of the following classes of antihypertensive agents can be used as drugs of choice: angiotensin converting enzyme inhibitors, long-acting calcium antagonists, selective beta1-adrenoblockers, and thiazide diuretics.
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PMID:[Arterial hypertension in a framework of metabolic syndrome: special features and principles of drug correction]. 1511 79

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.
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PMID:Treatment of metabolic syndrome. 1515 70

The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.
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PMID:Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management. 1630 67

The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. The major risk factors leading to this syndrome are physical inactivity and an atherogenic diet and cornerstone clinical feature is abdominal obesity or adiposity. In addition, patients usually have elevated triglycerides, low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters, hypertension, and elevated fasting blood glucose. Impaired fibrinolysis, increased susceptibility to thrombotic events, and raised inflammatory markers are also observed. Given that India has the largest number of subjects with type-2 diabetes in the world it can be extrapolated that this country also has the largest number of patients with the metabolic syndrome. Epidemiological studies confirm a high prevalence. Therapeutic approach involves intervention at a macro-level and control of multiple risk factors using therapeutic lifestyle approaches (diet control and increased physical activity, pharmacotherapy - anti-obesity agents) for control of obesity and visceral obesity, and targeted approach for control of individual risk factors. Pharmacological therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and orlistat can be tried to reduce weight and central obesity and jointly control the metabolic syndrome components. Other than weight loss, there is no single best therapy and treatment should consist of treatment of individual components of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia should be controlled initially with statins if there is an increase in LDL cholesterol. If there are other lipid abnormalities then combination therapy of statin with fibrates, nicotinic acid, or ezetimibe should be considered. For insulin resistance, drugs such as thiazolidinediones and renin-angiotensin system blockers are available. Available evidence suggests that angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS) may be more beneficial for treatment of hypertension in patients with metabolic syndrome compared to others as these drugs also prevent development of diabetes. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor (PPAR) agonists and cannabinoid receptor-1 antagonists, will broaden the horizons of the current treatment options. Fixed-dose combination polypharmacy using a single pill is an interesting concept that needs to be evaluated in long-term prospective trials in such patients.
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PMID:Management issues in the metabolic syndrome. 1721 77

Selected laboratory markers of nutritional state in patients treated with peritoneal dialysis (PD) are presented in this review. Parameters, which depend on intake of nutritional products and are related to consequences of nutrition, especially to development of abdominal obesity, are shown. Attention is paid on factors, which modify laboratory parameters of nutritional state, independently on quantity and quality of ingested products. These parameters include volume of extracellular water, inflammatory state, metrical age, duration of treatment with PD, metabolic acidosis, treatment with angiotensin converting enzyme inhibitors. Among laboratory parameters, which are related to excess of visceral fat tissue, the most important results of investigations on serum adipocytokine concentration and insulin resistance are presented, underlying their associations with anthropometric parameters of nutritional state of PD patients.
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PMID:[Laboratory markers of nutritional state in patients treated with peritoneal dialysis]. 1965 Apr 27

The metabolic syndrome was initially described as an insulin-resistance syndrome characterized by the clustering of metabolic traits such as high triglycerides, low high-density lipoprotein cholesterol, high blood pressure, abdominal obesity and different degrees of impaired glucose regulation. Although different definitions have been developed by various consensus groups, epidemiological studies demonstrate that they all associate the metabolic syndrome with a similar cardiometabolic risk, which is high for diabetes (ranging between three- and 20-fold), depending on the number of components and the inclusion of impaired fasting glucose, impaired glucose tolerance or both. The latter appear to indicate the failure of the beta cell to produce enough insulin to compensate for the increased demand due to insulin resistance. There is a hyperbolic relationship between insulin production and insulin sensitivity, which can be calculated by the disposition index. When this is altered there is a higher risk of developing Type 2 diabetes. There have been no clinical trials in subjects selected by the diagnosis of metabolic syndrome, but structured lifestyle changes have been tested in people with impaired fasting glucose/impaired glucose tolerance and have been able to reduce incident Type 2 diabetes by almost 50%, as long as a weight loss of at least 5% is achieved. Oral antidiabetic and anti-obesity drugs have also been successful to a lesser degree. Some fibrates have reduced or delayed incident diabetes. Extended-release niacin has a neutral effect and statins are controversial. ACE inhibitors and ARBs are the antihypertensive agents least associated with incident diabetes.
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PMID:Metabolic syndrome as a risk factor for diabetes. 2022 18


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