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 objectives of this study were to determine post-infarction drug therapy at discharge from hospital and at one year in the Basse Normandie region (France) and the management of risk factors, to compare them with the practice recommended by the French Society of Cardiology and other recent references. Patients whose medical expenses were exonerated by the Social Security for primary myocardial infarction without a history of angioplasty or of coronary bypass grafting between February and September 2002 were reviewed. The data was researched from the hospital, the patient, the attending physician and the data bases of the Social Security. Four hundred and fifteen patients were included. At discharge from hospital the percentages of prescriptions of recommended drugs were as follows: betablockers 85%, antithrombotics 99%, ACE inhibitors 75%, lipid lowering drugs 90%; the four drug families were associated in 63% of cases. There was no significant difference in prescription between hospital discharge and the twelfth months except with regards to ACE inhibitors (68%) and the association of the four drug groups (54%). The prevalence of smoking, hypertension, diabetes, overweight, obesity and dyslipidaemia were respectively 40, 39, 9, 44, 20 and 81% at the time of infarction. At one year, the prevalence of smoking had fallen significantly to 16%; only 10.3% of patients had uncontrolled hypertension and only 29% had not obtained the recommended therapeutic target for LDL-cholesterol. The authors conclude that this analysis shows an adequation of drug prescription to current recommendations and an improvement in risk factor management which should, however, be pursued.
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PMID:[Secondary prevention of myocardial infarction in the Basse-Normandie region]. 1629 40

Dietary calcium appears to play a pivotal role in the regulation of energy metabolism and obesity risk. High calcium diets attenuate body fat accumulation and weight gain during periods of over-consumption of an energy-dense diet and to increase fat breakdown and preserve metabolism during caloric restriction, thereby markedly accelerating weight and fat loss. This effect is mediated primarily by circulating calcitriol, which regulates adipocyte intracellular Ca(2+). Studies of human adipocyte metabolism demonstrate a key role for intracellular Ca(2+) in regulating lipid metabolism and triglyceride storage, with increased intracellular Ca(2+) resulting in stimulation of lipogenic gene expression and lipogenesis and suppression of lipolysis, resulting in adipocyte lipid filling and increased adiposity. Moreover, the increased calcitriol produced in response to low calcium diets stimulates adipocyte Ca(2+) influx and, consequently, promotes adiposity, while higher calcium diets inhibit lipogenesis, promote lipolysis, lipid oxidation and thermogenesis and inhibit diet-induced obesity in mice. Notably, dairy sources of calcium exert markedly greater effects in attenuating weight and fat gain and accelerating fat loss. This augmented effect of dairy products versus supplemental calcium has been localized, in part, to the whey fraction of dairy and is likely due to additional bioactive compounds, such as angiotensin converting enzyme (ACE) inhibitors in dairy, as well as the rich concentration of branched chain amino acids, which act synergistically with calcium to attenuate adiposity; however, these compounds do not fully account for the observed effects, as whey has significantly greater bioactivity than found in these compounds. These concepts are confirmed by epidemiological data as well as recent clinical trials which demonstrate that diets which include at least three daily servings of dairy products result in significant reductions in body fat mass in obese humans in the absence of caloric restriction and markedly accelerates the weight and body fat loss secondary to caloric restriction compared to low dairy diets. These data indicate an important role for dairy products in both the ability to maintain a healthy weight and the management of overweight and obesity.
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PMID:The role of dairy foods in weight management. 1637 53

Patients with type 2 diabetes often also exhibit additional features of the metabolic syndrome. These include specifically central obesity triggering development and maintenance of diabetes together with arterial hypertension, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Chronic therapy of the metabolic syndrome in diabetics after coronary bypass surgery focuses on changes in lifestyle, i.e., cessation of smoking, changes in nutrition and increase in physical activity. Nutrition aims at fat reduction and modification to reduce saturated fatty acids, to allow mono- and polyunsaturated fatty acids instead, and moderate alcohol consumption. High fiber and complex carbohydrate diet complete the recommendations. Nutrition therapy connected to increases in physical activity are aimed at reducing weight in overweight and obese subjects, which should reduce their body weight by 5 to 10% within about 6 months. Normal weight subjects benefit from increases in physical activity by lipid and glucose regulation as well as by reduction in mortality.Diabetes-specific therapy aims at normoglycemia including postprandial blood glucose levels, reduces blood pressure supported by ACE inhibitors and aims at weight reduction. Reduction of LDL-cholesterol is the first line therapy, also diminishing small-dense LDL particles. Decreasing triglycerides and increasing HDL-cholesterol are further lipid-regulating aims. Specifically diabetics after coronary bypass surgery need LDL-cholesterol levels below 70 mg/d (1.8 mmol/L) and triglycerides below 150 mg/dL (1.7 mmol/L). In addition, in males HDL-cholesterol should be at least above 40 mg/dl (1 mmol/L), in females above 50 mg/dL (1.3 mmol/L).
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PMID:[Long-standing therapy of the metabolic syndrome in diabetics after coronary artery bypass surgery]. 1659 37

Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.
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PMID:Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. 1713 May 9

The contribution of angiotensin I-converting enzyme insertion-deletion polymorphism (ACE I/D) to salt-sensitivity hypertension has been extensively studied by means of salt-loading tests, but whether or not the interaction with daily salt intake affects blood pressure still remains to be clarified. We therefore conducted a cross-sectional study of 284 Japanese male workers (age range, 20-64 years) to examine the effect of ACE I/D genotype and daily salt intake on hypertension. Blood pressure was measured and the ACE I/D was identified by polymerase chain reaction (PCR). Daily salt intake was calculated from a food frequency questionnaire (FFQ). In multivariate analyses, we explored the interaction of ACE I/D and salt intake by means of logistic regression analysis and multiple linear regression analysis. ACE I/D per se was not associated with blood pressure levels or hypertension. ACE I/D interacted with daily salt intake and correlated with hypertension (p for interaction = 0.047). In the ID+II genotype, hypertension was increased by high salt intake (p = 0.005), while in the DD genotype it was not (p = 0.257). The interaction was more prominent in the overweight group (p = 0.039) than in non-overweight group. In the overweight group, high salt intake induced a 10.5 mmHg higher diastolic blood pressure in the ID+II genotype than in the DD genotype (p = 0.042). Our results suggest that ACE I/D and daily salt intake constitute a gene-environment interaction, which may be further modulated by overweight.
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PMID:Interaction of angiotensin I-converting enzyme insertion-deletion polymorphism and daily salt intake influences hypertension in Japanese men. 1728 61

The TROPHY study was designed to show the feasibility of pharmacological prevention of hypertension with respect to the group of patients with "prehypertension" as defined by the JNC VII recommendations. This clinical trial compared candesartan 16 mg/day with placebo and the result at 4 years was a reduction in the relative risk of developing hypertension of 15.6%. The antihypertensive drug delayed the onset of hypertension in a mainly overweight masculine population. Staessen, Zhu and O'Brien's groups suggest measuring an index of arterial rigidity obtained from ambulatory blood pressure monitoring: the ambulatory arterial stiffness index (AASI). This is calculated as [1- slope of systolic/diastolic pressure]. The reference values for AASI vary with age from 0.50 to 0.70. The CAFE study, a spin-off of the ASCOT trial, showed that the central blood pressure decreased more than the peripheral blood pressure with the association amlodipine-perindopril as compared with atenolol and a thiazide diuretic. The capacity of an antihypertensive drug or an association of antihypertensives to decrease the central blood pressure could be a pertinent factor of evaluation to be taken into account in the interpretation of clinical trials. The study of the Italian cohort PAMELA showed a progressive increase in cardiovascular and global mortality with respect to the findings of increased blood pressure by one, two or three methods of measurement (at the office, at home, ambulatory) compared with patients declared normotensive by the same methods. This registry confirmed the implication of masked hypertension on cardiovascular prognosis and also showed that "white coat" hypertension was not completely benign. The "3 cities" study is a French epidemiological study of persons over 65 years of age. The control of the blood pressure of the treated elderly hypertensives was 57% in men and 70% in women when the cut-off was 160/95 mmHg and 31% for all patients in a cut-off level of 140/90 mmHg. Lafontan et al. are studying the mobilisation of fat induced by exercise, resistant to betablockers therapy and attributed to natriuretic peptides. This metabolic pathway could be of relevance in the metabolic syndrome and in cardiac failure. Renin inhibitors, such as aliskiren, are being developed. The outlook is the possible use of these drugs with ACE inhibitors or angiotensin II inhibitors, taking into account the risk/benefit ratio.
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PMID:[The best of hypertension in 2006]. 1740 64

In myocardial ischaemia and heart failure, beta-blockers with intrinsic sympathomimetic activity (ISA) e.g. pindolol, xamoterol, bucindolol, nebivolol, have performed poorly in reducing morbidity and mortality. In both indications beta-1 blockade is the vital active ingredient. Beta-1 blockade (bisoprolol) is now an alternative first-line choice to Ace-inhibition in the treatment of heart failure. The therapeutic role of beta-blockers in hypertension is less well understood, particularly since the new recommendations in the UK from the NICE committee stating that: 1. beta-blockers are no longer preferred as a routine initial therapy, 2. the combination with diuretics is discouraged due to the risk of induced diabetes, and 3. in younger patients first-choice initial therapy should be an ACE-inhibitor. Recent data from the Framingham Heart Study and other epidemiological studies have indicated that the development of diastolic hypertension in younger subjects is closely linked to weight-increase and an increase in peripheral resistance; such subjects have a high adrenergic drive and cardiac output. In contrast, elderly systolic hypertension mostly arises de novo via poor vascular compliance. Thus in younger, probably overweight, hypertensives (including diabetics) first-line beta-blockade has performed well in preventing myocardial infarction (a fact hidden by meta-analyses that do not take age into account). Conversely, in elderly hypertensives first-line beta-blockade (atenolol) has performed poorly in reducing cardiovascular risk (due to partial beta-2 blockade atenolol evokes metabolic disturbance and does not improve vascular compliance, or effectively lower central aortic pressure or reverse left ventricular hypertrophy). Thus beta-blockers like atenolol are ill-equipped for first-line therapy in elderly hypertension. Some beta-blockers, e.g. bisoprolol (up to 10 mg/day is highly beta-1 selective) and nebivolol (beta-2/3 intrinsic sympathomimetic activity), do improve vascular compliance and cause no metabolic disturbance. Beta-blockers as second-line to low-dose diuretics (which, by improving vascular compliance and increasing sympathetic nerve activity, create an optimal environment for beta-blockade) in elderly hypertension (including diabetics) have performed well in reducing cardiovascular events (this combination has the added bonus of reducing the risk of bone fracture by about 30%). Meta-analyses which include studies where it is unclear whether a diuretic or beta-blocker was a first-line therapy will dilute the benefit stemming from first-line diuretic/second-line beta-blockade. Hypertensives (of all ages) with ischaemia are well suited to beta-blockade.
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PMID:Are we misunderstanding beta-blockers. 1743 71

The coexistence of hypertension and type 2 diabetes considerably increases the risk for cardiovascular and renal complications, not only after manifestation of the diseases, but also in the range of high-normal blood pressures and prediabetic states. According to recent guidelines, patients with type 2 diabetes should be treated if the blood pressure is in the high-normal (previously normal) range (130-139/85-90 mmHg), sometimes even with blood pressures in the normal oder low prehypertensive range (120-129/80-85 mmHg). In any case, blood pressure should be reduced < 130/80 mmHg, if tolerated < 125/75 mmHg. The target for diabetic patients with microalbuminuria or nephropathy is below 125/75 mmHg. All blood pressure goals cited refer to office or clinic blood pressure measurements. The corresponding values for home (self) or ambulatory blood pressure measurement during the day are lower by 5-10 mmHg for systolic and 5 mmHg for diastolic blood pressures. The proper management of patients with type 2 diabetes has to be multifactorial, aiming at controlling blood pressure, hyperglycemia and dyslipidemia by using both lifestyle changes (reduction of sodium and fat intake, regular physical activity, weight loss in overweight patients, smoking cessation) and drug therapy. Antihypertensive treatment should be started with a (fixed) combination, preferably containing an inhibitor of the renin-angiotensin system such as ACE inhibitors or AT(1)-receptor blockers and either a diuretic (preferably indapamide) or a calciumantagonist rather than combining thiazide diuretics and beta-blockers.
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PMID:[Treatment of hypertensive type 2 diabetics: too late, too little]. 1856 13

Cardiovascular diseases (CVD) are the leading cause of mortality in Croatia and in Europe. Primary prevention of CVD involves intervention before the onset of disease, and prevention of modifiable risk factors, i.e. cigarette smoking, hyperlipidemia, arterial hypertension, diabetes mellitus, inactivity, obesity. These risk factors are strongly associated and lead to impaired vascular endothelial function, chronic injury of endothelium, platelet activation and aggregation, atherosclerotic plaque formation, and in the end manifestation of CVD. The risk of any coronary event increases exponentially when two or more risk factors are present. Aside from conventional factors, it has been demonstrated that raised levels of C-reactive protein (CRP), cytokines, homocysteine and fibrinogen are also important promotors of the disease, pointing to partially inflammatory nature of coronary atherosclerosis. The effects of risk factors such as smoking, arterial hypertension and hyperlipidemia on vascular endothelium are proven to be reversible. According to Guidelines on Cardiovascular Disease Prevention in Clinical Practice of the European Society of Cardiology (2007), population is advised to follow the formula 0 3 5 140 5 3 0. It suggests that crucial measures in preserving cardiovascular health are as follows: no smoking (0), walking 3 km daily or 30 minutes of any moderate activity (3), blood pressure less than 140 mm Hg systolic (140), total blood cholesterol less than 5 mmol/L (5), LDL cholesterol less than 3 mmol/L (3), avoidance of overweight and diabetes (0). There are many studies proving the beneficial effects of statins and ACE inhibitors in improving endothelial function and endorsing primary prevention.
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PMID:[Primary prevention of cardiovascular disease]. 1968 67

In the PREVENIR-5 study, artificial neural networks (NN) were applied to a large sample of patients with recent first acute coronary syndrome (ACS) to identify determinants of persistence of evidence-based cardiovascular medications (EBCM: antithrombotic + beta-blocker + statin + angiotensin converting enzyme inhibitor-ACEI and/or angiotensin-II receptor blocker-ARB). From October 2006 to April 2007, 1,811 general practitioners recruited 4,850 patients with a mean time of ACS occurrence of 24 months. Patient profile for EBCM persistence was determined using automatic rule generation from NN. The prediction accuracy of NN was compared with that of logistic regression (LR) using Area Under Receiver-Operating Characteristics-AUROC. At hospital discharge, EBCM was prescribed to 2,132 patients (44%). EBCM persistence rate, 24 months after ACS, was 86.7%. EBCM persistence profile combined overweight, hypercholesterolemia, no coronary artery bypass grafting and low educational level (Positive Predictive Value = 0.958). AUROC curves showed better predictive accuracy for NN compared to LR models.
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PMID:Prediction of persistence of combined evidence-based cardiovascular medications in patients with acute coronary syndrome after hospital discharge using neural networks. 2159


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