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)

The risk for cardiovascular complications is already substantially increased in persons with borderline elevation of arterial pressure (141-159/90-94 mmHg and transiently below). It increases progressively with higher grades of hypertension. The main aim of treatment is thus a significant improvement in survival for the patient. Persons with raised blood pressure (BP) have often additional cardiovascular risk factors such as deranged carbohydrate metabolism, dyslipidemia, left ventricular hypertrophy, smoking and others. Treatment of hypertensive patients should thus not only normalize BP but should at the same time reduce associated risk factors or at least not increase them. Conventional antihypertensive treatment based on thiazides in high doses or beta-blocking agents led to marked reduction of strokes and heart failure, but did not satisfactorily reduce coronary heart disease or sudden cardiac death. It has been suspected that other cardiac risk factors are insufficiently influenced or eventually even deteriorated by conventional therapy, thus counteracting partly a beneficial effect of lowered BP. Beta-blockers however have at least a secondary preventive effect after myocardial infarction. Newer antihypertensive drugs such as ACE-inhibitors, calcium antagonists and alpha 1-blockers reduce left ventricular hypertrophy and are at least neutral with regard to metabolism of lipids and carbohydrates. The non-thiazide diuretic indapamide and the serotonin (S2-) blocker ketanserin likewise are neutral with regard to glucose and lipid metabolism. The efficacy of these new drugs regarding long term survival is as yet undetermined. Persisting borderline or established hypertension should as a rule always be approached with basic non-pharmacologic measures: loss of overweight, reduction of alcohol intake, exercise, avoidance of high salt foods, abstention from smoking and withdrawal of BP-raising drugs. If antihypertensive medication is indicated, potential first line drugs are ACE-inhibitors, calcium antagonists, beta-blockers, thiazides at low dose, indapamide, ketanserin, the alpha 1-blocker prazosin and others; initially as monotherapy, if needed in combinations of 2 or 3. Older patients or those will with additional disturbances such as diabetes, hypercholesterolemia, nephropathy, heart failure, ischemic heart disease, arrhythmias, claudication, asthma and others need problem-adjusted modifications of treatment.
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PMID:[Antihypertensive therapy in the nineties]. 153 54

The study was undertaken to evaluate the development and association of parameters related to the metabolic syndrome during celiprolol treatment. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed on 25 nondiabetic patients with controlled hypertension and dyslipidemia. The tests were carried out during the patients' previous antihypertensive monotherapy (beta- or Ca-blocker, or an ACE inhibitor), and after 6 and 12 months of celiprolol treatment. About one third of patients were randomized to a control group in which treatment was kept unchanged. Insulin sensitivity index (ISI), measured by the euglycemic clamp test, increased 35% in the celiprolol group at 6 months and remained at that level at 12 months, independent of the previous treatment (p = 0.03, compared to the change in the control group). During a 2 hour OGTT, incremental glucose area under the curve (AUC) decreased from 4.5 to 1.9 hr x mmol/l during 6 months of celiprolol treatment, and decreased further to 1.5 hr x mmol/l at 12 months (p < 0.001). Insulin AUC decreased from 113 to 72 hr x mU/l, and decreased further to 68 hr x mU/l (p < 0.01). All insulin parameters in OGTT were highly significant (p < 0.0001) and inversely associated with ISI. Insulin AUC had the best linear correlation with ISI (r = -0.682, p < 0.0001). Glucose parameters in OGTT correlated only weakly and inversely with insulin sensitivity. From the fasting serum lipids, triglycerides showed an inverse (p < 0.001) and HDL a weak (p < 0.05) positive association with ISI. Four out of 20 metabolic, clinical, and demographic parameters proved to be independently significant predictors for ISI in multiple regression analysis. These were insulin AUC, fasting insulin levels, triglyceride values, and age. The coefficient of determination in this four-parameter linear model was 69%. In this preliminary, observer-masked trial with a limited control group, celiprolol improved the impaired insulin sensitivity and glucose tolerance of dyslipidemic hypertensive patients. A fairly predictive model can be formulated to evaluate the peripheral insulin sensitivity of hypertensive patients with suspected metabolic syndrome using OGTT with serum insulin determinations.
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PMID:Association between serum lipids, glucose tolerance, and insulin sensitivity during 12 months of celiprolol treatment. 766 96

A survey was made on a sample of Italian practitioners to evaluate the diagnostic and therapeutic approach to arterial hypertension. A questionnaire was distributed containing thirteen questions, that was personally completed and restituted by 919 physicians. The first datum that was evidenced was that the hypertensive patient observed by the practitioner is, in the great majority of cases, in old age. The percentage of patients with concomitant diseases (dyslipidemia, diabetes, obesity, cardiac failure) is very high. The blood pressure measurement is correct, especially by expert physicians. By contrast, the younger physicians tend to prescribe further diagnostic instrumental measures. The antihypertensive therapy is prescribed very accurately. According to the sample studied, the first line drugs that are more often recommended are the ACE-inhibitors, especially by younger physicians. From this survey a prualently positive judgment by the physicians emerged in relation to the available drugs for the anti-hypertensive therapy, as consequence of the observation of satisfactory therapeutic efficacy and tolerability by the patients.
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PMID:[The diagnostic-therapeutic approach to hypertension. A study of 1000 Italian physicians]. 770 40

Insulin resistance and reactive hyperinsulinemia occur not only in patients with obesity, impaired glucose tolerance or non-insulin-dependent (Type 2) diabetes mellitus, but also in many non-obese, non-diabetic individuals with essentiell hypertension and their normotensive, lean young offsprings. The common coexistance of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent occurrence of hypertension as well as dyslipidemia, obesity and diabetes Type 2 in a given individual. In the pathogenesis of hypertension, inappropriate vasoconstriction and/or a structural vasculopathy appears to be an important and ultimate causative event. Several pressor mechanisms are discussed and a distinct sodium retention appears to be almost obligatory associated with diabetes mellitus, while essential and particularly obesity-associated hypertension involves predominantly a tendency for sympathetic activation. Acute hyperinsulinemia on one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis. Insulin resistance affecting certain transmembrane cation transporters might lead to an elevation of intracellular cytosolic calcium levels thereby inducing inappropriate vasoconstriction. Nevertheless, whether insulin resistance and hyperinsulinemia contribute to the pathogenesis of hypertension per se is still unproven. Considering antihypertensive drugs, thiazide diuretics given in medium or high dosage as well as beta-blockers appear to promote insulin resistance, reactive hyperinsulinemia and dyslipidemia. Almost all calcium antagonists and the conventional sympthatolytics are metabolically neutral, while ACE-inhibitors and alpha 1-blockers tend to improve insulin resistance. In Type 2 diabetic patients, ACE-inhibitors exert in addition to their antihypertensive a potentially useful anti-diabetic effect. Nevertheless, the prognostic relevance of the metabolic side effects of antihypertensive drugs awaits further clarification.
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PMID:[Insulin resistance and arterial hypertension]. 771 73

Eight patients with biopsy-proven primary nephrotic syndrome were included in an open, prospective, two-year study of lovastatin. One patients was withdrawn after 6 months due to an asymptomatic rise in creatinine phosphokinase, which was rapidly reversed after interruption of lovastatin. In the remaining patients, treatment was well-tolerated and produced no side effects. After 2 years of treatment, these 7 patients had decreases in total cholesterol from 446 +/- 165 to 250 +/- 57 mg/dl (p < 0.001), LDL cholesterol from 343 +/- 121 to 174 +/- 49 mg/dl (p < 0.001), Apo B lipoprotein from 162 +/- 60 to 108 +/- 42 mg/dl (p < 0.05), triglycerides from 336 +/- 273 to 182 +/- 71 mg/dl (p < 0.04). There was no change in HDL cholesterol. The LDL/HDL cholesterol and the total/HDL cholesterol ratios fell from 15.0 +/- 12.1 and 19.1 +/- 17.2 mg/dl before the study to 4.4 +/- 1.2 and 6.3 +/- 1.6 mg/dl, respectively, at 2 years. A decrease in proteinuria from 8.6 +/- 4.6 to 5.0 +/- 3.7 g/24 h (p < 0.02) was noted in 4 patients on concomitant ACE inhibitor therapy. Renal function remained stable in all patients throughout the study, except for one whose moderate impairment progressed to end-stage renal failure requiring dialysis 3 months poststudy. We conclude that long-term lovastatin in patients with primary nephrotic syndrome is an effective and generally safe treatment for accompanying dyslipidemia.
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PMID:Long-term effect of lovastatin on lipoprotein profile in patients with primary nephrotic syndrome. 805 Feb 7

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
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PMID:Hyperinsulinemia--how innocent a bystander? 829 79

Hypertension is not solely a phenomenon of elevation of systemic blood pressure. It frequently occurs in association with a great deal of metabolic derangement's and should never be regarded as coincidental only. Furthermore, a knowledge of these metabolic derangements may provide a clue to unveil the underlying mechanisms how essential hypertension and its associated complications arise. Therefore we devoted our attention to platelet dysfunction and dyslipidemia which are closely associated with atherosclerosis-the commonest complication of hypertension. We found there exists enhanced platelet aggregation in essential hypertension and a variety of its associated atherosclerotic diseases. Such an aberration in platelet function may be modified after administration of antihypertensive medications such as angiotensin converting enzyme (ACE) inhibitors, calcium channel blockades, beta blockades and dietary manipulation. We also demonstrated the close association between hypertension and its associated atherosclerotic complications and abnormal lipids profile. Hypertriglyceridemia which was initially regarded unimportant in the pathogenesis of atherosclerosis is found to be closely related to hypertension. In an intensive review, we found that people in Taiwan has experienced a huge increase in dietary calories and total fat consumption. In order to solve this emerging problem, a national guideline for diagnosis and management of lipid disorders in Taiwan was developed and announced. Through these efforts, we hope we can reduce the cardiovascular morbidity and mortality in Taiwan and even extend our experience to other countries.
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PMID:Thrombogenic and lipid risk factors in hypertension and coronary artery disease. 868 58

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and shown to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. Studies have shown that in patients with insulin-dependent diabetes and proteinuria, lowering systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death independent of their effect on systemic blood pressure. In studies with small numbers of patients, dietary protein restriction has also been shown to slow the rate of decline of renal function. New potential interventions currently undergoing study include treatment with aldose reductase inhibitors, treatment with inhibitors of the formation of advanced glycosylation end-products, treatment of dyslipidemia, and a variety of other less well-studied interventions.
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PMID:Therapeutic interventions for nephropathy in type I diabetes mellitus. 914 77

In subjects with coronary artery diseases (obstructive and vasospastic angina pectoris (AP)) who have no diabetes, hypertension, obesity and physical inactivity, insulin sensitivity was significantly reduced with compensated hyperinsulinemia on OGTT. Insulin resistance significantly correlated with coronary atherosclerosis score. In vasospastic AP (VAP), those who fulfilled more than 3 risk factors out of 5 (hyperinsulinemia, obesity, glucose intolerance, hypertension, dyslipidemia) consist of 70 and 40% for smokers and nonsmokers respectively. Insulin resistance syndrome who fulfilled all the criteria was 9-10% for VAP. In atherothrombotic brain infarction (ATTI) with the same exclusion criteria, the similar insulin resistance and hyperinsulinemia have been observed, but not in embolic (cardiac origin) or lacunar infarction. In ATTI, high TG and apo B with low HDL-chol were noted in blood. In essential hypertension without diabetes and obesity, hyperinsulinemia was noted in 25-35% and insulin resistance in 56-88%. Reduction of blood pressure with alpha blocker (bunazosin), ACE inhibitor (cilazapril), long-acting Ca++ blocker (amlodipine) significantly improved lowered insulin sensitivity. Insulin resistance rather than hyperinsulinemia is more closely associated with blood pressure. Cardiovascular diseases (vasospastic and obstructive AP, brain cortical artery diseases) are prone to develop diabetes because of insulin resistance and also promote the generation of cumulative risk factors resulting in a vicious cycle. Efforts to alleviate insulin resistance is crucial for the primary and secondary prevention of cardiovascular diseases.
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PMID:Clinical impact of insulin resistance syndrome in cardiovascular diseases and its therapeutic approach. 924 Jul 71

OBESITY AND RISK OF MORBIDITY: Obesity is becoming an increasingly important factor in the pathogenesis of hypertension, dyslipidemia and diabetes, which together with hyperinsulinemia comprise the deadly quartet of the insulin resistance syndrome. Obesity in the absence of these other factors is only a minor risk factor, but most obesity is accompanied by one or more of these, worsening the prognosis. The presence of obesity complicates the management of hypertension, probably in large part because of the concomitant insulin resistance which adds to the pathogenetic mechanisms and subtracts from the therapeutic efficacy of many antihypertensive regimens. Unfortunately, some of the agents used to reduce obesity may further aggravate the problem through their stimulation of sympathetic nervous activity. Nonetheless, in the treatment of hypertension in most obese patients who have relatively little excess risk, attempts to reduce body weight should be attempted first, through sensible dietary restrictions, increased aerobic exercise and judicious use of non-hypertensinogenic appetite suppressants. Thereby, additional motivation to lose weight may be provided by the potential of escaping or at least delaying antihypertensive drug therapy. TREATMENT OF HIGHER-RISK OBESE INDIVIDUALS: Those obese hypertensive individuals at greater risk should be immediately started on antihypertensive drug therapy along with attempts to reduce the obesity. The choice of initial and subsequent therapy should take the patient's individual needs into account. For those with dyslipidemia or diabetes, diuretics and beta-blockers should be avoided unless there are specific indications for their use (e.g. reactive sodium retention or postmyocardial infarction). In such patients, an alpha-blocker, an angiotensin converting enzyme inhibitor or a calcium antagonist may be more appropriate. If the first drug is not sufficient, combination therapy should be considered. A diuretic may be needed to overcome reactive sodium retention. Because most obese hypertensive individuals will not be able to lose much weight, effective antihypertensive drug therapy will usually be indicated.
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PMID:Obesity in hypertension: effects on prognosis and treatment. 953 95


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