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)

Elevated blood pressure is a risk factor for a variety of cardiovascular disorders, including coronary heart disease, peripheral vascular disease, cardiac failure and cerebrovascular disease. The prevailing view is that an elevated systolic rather than diastolic blood pressure is the major contributor in mortality and morbidity attributed to cardiovascular disorders. Isolated high systolic blood pressure, especially in the elderly, is a major risk factor and should undoubtedly be a target for drug treatment. In the general population, systolic and diastolic blood pressure are highly correlated, and thus it is difficult to dissociate the effects of these two components of the blood pressure and specifically ascribe cardiovascular risk factors to just elevated systolic blood pressure. Therefore, the goal in therapy of an individual with hypertension must be to reduce elevated systolic and diastolic blood pressure in order to reduce mortality and morbidity. ACE and neutral peptidase inhibitors are a new class of drugs that may be beneficial in the treatment of patients with hypertension and heart failure. They may also be useful in the treatment of diabetic patients with hypertension and/or heart failure. Drugs of this class are dual inhibitors of ACE and neutral endopeptidase, and are capable of affecting vascular tone and fluid balance. They are capable of producing vasodilatation by virtue of inhibiting the production of angiotensin II, degradation of natriuretic peptides and bradykinin. They also appear to promote natriuresis and diuresis by amplifying the actions of natriuretic peptidase and reducing aldosterone effects. In addition, they should also attenuate trophogenic actions of the renin angiotensin system and the sympathetic nervous system. Omapatrilat is one drug that appears to be at the advanced stages of clinical development. This drug has been shown to be quite effective in the treatment of hypertension. Evidence also seems to indicate that treatment with omapatrilat results in a higher tendency towards preventing death and worsening heart failure when compared with treatment with a pure ACE inhibitor in patients with advanced heart failure. Overall safety with omapatrilat appears to be good, but like other ACE inhibitors the incidence of cough is higher when compared with placebo. Other common adverse effects noted are headaches, facial flushing/warm sensation, dizziness, nausea and dyspnoea. Of greater concern is the occurrence of angio-oedema, the true incidence of which remains to be fully established as part of the published medical literature.
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PMID:Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. 1501 94

The association between erectile dysfunction (ED) and peripheral vascular disease (PVD) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, Health Insurance Portability and Accountability Act compliant database and includes complete medical histories for more than 17 million managed-care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12 825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of PVD that accounted for age at ED diagnosis, smoking, obesity and medications including angiotensin converting enzyme (ACE) inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a 75% increase in risk for PVD (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.06, 2.90) after adjusting for age at ED diagnosis, smoking, obesity and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend towards increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men aged 30-39 years, it was noted that patients aged 40-44 years were 2.1 times more likely to develop PVD (OR = 2.07, 95% CI = 0.89, 4.81), 45-49-year-old men were also more than twice as likely to have PVD (OR = 2.32, 95% CI = 1.03, 5.22), and 50-55-year-old patients had a three-fold increased risk of developing PVD (OR = 3.00, 95% CI = 1.40, 6.43). The results of this study indicate that ED may serve as a marker for PVD. The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.
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PMID:Is erectile dysfunction predictive of peripheral vascular disease? 1500 59

Prevalence of complications of type 2 diabetes in a remote Australian Indigenous community was measured as part of a population survey of risk factors for diabetes and cardiovascular disease. Information was obtained from history, clinical examination, blood sample and medical records. Forty-three diabetic participants (six newly diagnosed) were assessed from a sample of 339 (12% diabetes prevalence); mean age 50 (range 31-67), duration of diabetes 5.6 (0-15) years, 40% male. Risk factors/complications: 70% with >/= 25, 50% cigarette smokers, HbA1c 8.5 (S.D. 2.9)%, cholesterol 4.8 (0.8)mmol/l, triglycerides 2.7 (1.6)mmol/l, HDL 0.83 (0.2)mmol/l; 60% had albuminuria (micro 38%, macro 22%), 47% were hypertensive, 7% (n = 2) had retinopathy, 24% had peripheral neuropathy, none had peripheral vascular disease, 14% had documented coronary vascular and one participant cerebrovascular disease. Of 37 with previously diagnosed diabetes: 43% were on aspirin, 65% on metformin, 80% with albuminuria on ACE inhibitors. Four additional diabetic participants (not studied) were receiving renal dialysis elsewhere. The results demonstrate on the one hand, very high indices of cardiovascular risk (smoking, hypertension, dyslipidaemia and albuminuria) and on the other, good quality primary health care providing good detection and follow up management of type 2 diabetic patients.
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PMID:Diabetes care and complications in a remote primary health care setting. 1506 99

The efficacy of angiotensin converting enzyme (ACE) inhibitors in treatment of renovascular disease has been controversial. It has been reported that patients with incidental atherosclerotic renal artery stenosis (ARAS) are sometimes treated with ACE inhibitors before being considered for renal revascularization. This study was designed to describe the frequency and the characteristics of patients with incidental ARAS, and to examine the frequency of ACE inhibitor usage in such patients. We studied a cohort of consecutive patients undergoing abdominal aortography at the time of cardiac catheterization. Patients were stratified and compared based on the presence and severity of ARAS. ARAS (> or =50%) was present in 146 (17.0%) of 859 evaluable patients. Factors independently related to the presence of ARAS were age (odds ratio (OR)=1.07, p < 0.001), severity of coronary artery disease (OR=2.13, p < 0.001) and peripheral vascular disease (OR=1.79, p = 0.021). Among all patients with ARAS, the percentage of ACE inhibitor usage was 74.7% (109/146). Among patients with severe ARAS, moderate ARAS, mild ARAS, insignificant ARAS and normal renal arteries, the percentage of ACE inhibitor usage was 85.7% (95% confidence interval (CI): 69-100%), 82.9% (95% CI: 71-95%), 68.5% (95% CI: 59-78%), 68.6% (95% CI: 55-82%) and 53.9% (95% CI: 50-58%), respectively (contingency coefficient=0.17, p < 0.001). In patients with severe ARAS, ACE inhibitor use, calcium channel blocker use and diuretic use were shown to correlate significantly with serum creatinine levels after controlling for potential confounding factors. In this study, ACE inhibitors were used commonly in patients with incidental ARAS; the frequency of ACE inhibitor use correlated with the severity of ARAS.
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PMID:Angiotensin-converting enzyme inhibitor usage in patients with incidental atherosclerotic renal artery stenosis. 1519 81

Hypertension and osteoporosis are two major chronic diseases affecting the elderly. A cross-sectional study of 3887 Chinese men (n = 1958) and women (n = 1929) was used to explore the association between angiotensin converting enzyme inhibitor (ACEI) use and bone mineral density (BMD). The participants were aged 65 years and above, and were recruited using a combination of private solicitation and public advertising from community centers, housing estates, and the general community in Hong Kong. Demographic, medical, and lifestyle information was obtained from face to face interviews using standardized questionnaire, and physical examination measurements included anthropometry, tibial, and brachial systolic blood pressures, femoral neck, total hip, and lumbar spine BMD. In multiple regression analyses, after adjusting for age, weight, height, thiazide, beta-blocker, calcium channel blocker, statin, corticosteroid, and calcium supplement use, history of diabetes, heart disease, peripheral vascular disease, cigarette smoking, alcohol intake, and physical activity level, ACEI use was associated with higher femoral neck BMD (+0.015 g/cm2, P = 0.035) in women, and higher femoral neck (+0.015 g/cm2, P = 0.017), total hip (+0.016 g/cm2, P = 0.021), and lumbar spine (+0.043 g/cm2, P < 0.001) BMD in men. Thiazide use was associated with higher BMD at all three sites in general, although associations with BMD increase at the total hip (P = 0.07) and femoral neck (P = 0.09) were weak in men. Calcium channel blocker use was only significantly associated with BMD increase at the lumbar spine (P = 0.03) in women, and beta-blocker use did not have significant associations with BMD at any site. This study suggests that in addition to thiazide diuretics ACEI may have possible benefits in treating not only hypertension but also osteoporosis among older Chinese.
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PMID:Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. 1625 80

Treatment of migraine presents special problems in the elderly. Co-morbid diseases may prohibit the use of some medications. Moreover, even when these contraindications do not exist, older patients are more likely than younger ones to develop adverse events. Managing older migraine patients, therefore, necessitates particular caution, including taking into account possible pharmacological interactions associated with the greater use of drugs for concomitant diseases in the elderly. Paracetamol (acetaminophen) is the safest drug for symptomatic treatment of migraine in the elderly. Use of selective serotonin 5-HT(1B/1D) receptor agonists ('triptans') is not recommended, even in the absence of cardiovascular or cerebrovascular risk, and NSAID use should be limited because of potential gastrointestinal adverse effects. Prophylactic treatments include antidepressants, beta-adrenoceptor antagonists, calcium channel antagonists and antiepileptics. Selection of a drug from one of these classes should be dictated by the patient's co-morbidities. Beta-adrenoceptor antagonists are appropriate in patients with hypertension but are contraindicated in those with chronic obstructive pulmonary disease, diabetes mellitus, heart failure and peripheral vascular disease. Use of antidepressants in low doses is, in general, well tolerated by elderly people and as effective, overall, as in young adults. This approach is preferred in patients with concomitant mood disorders. However, prostatism, glaucoma and heart disease make the use of tricyclic antidepressants more difficult. Fewer efficacy data in the elderly are available for selective serotonin reuptake inhibitors, which can be tried in particular cases because of their good tolerability profile. Calcium channel antagonists are contraindicated in patients with hypotension, heart failure, atrioventricular block, Parkinson's disease or depression (flunarizine), and in those taking beta-adrenoceptor antagonists and monoamine oxidase inhibitors (verapamil). Antiepileptic drug use should be limited to migraine with high frequency of attacks and refractoriness to other treatments. Promising additional strategies include ACE inhibitors and angiotensin II type 1 receptor antagonists because of their effectiveness and good tolerability in patients with migraine, particularly in those with hypertension. Because of its favourable compliance and safety profile, botulinum toxin type A can be considered an alternative treatment in elderly migraine patients who have not responded to other currently available migraine prophylactic agents. Pharmacological treatment of migraine poses special problems in regard to both symptomatic and prophylactic treatment. Contraindications to triptan use, adverse effects of NSAIDs, and unwanted reactions to some antiemetics reduce the list of drugs available for the treatment of migraine attacks in elderly patients. The choice of prophylactic treatment (beta-adrenoceptor antagonists, calcium channel antagonists, antiepileptics, and more recently, some antihypertensive drugs) is influenced by co-morbidities and should be directed at those drugs that are believed to have fewer adverse effects and a better safety profile. Unfortunately, for most of these drugs, efficacy studies are lacking in the elderly.
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PMID:Practical considerations for the treatment of elderly patients with migraine. 1687 31

Peripheral vascular disease is an atherosclerotic process. It has been suggested that angiotensin converting enzyme insertion/deletion polymorphism is associated with atherosclerosis. The aim of this study was to investigate the role of the insertion/deletion polymorphism of the angiotensin-converting enzyme in Turkish patients with peripheral vascular disease in Western part of Turkey. We also investigated the relationship between serum angiotensin converting enzyme activity and distribution of genotypes in both patients and control group. The study group consisted of 78 patients with peripheral vascular disease. The control group consisted of 73 healthy adults. Serum angiotensin converting enzyme activities in patients were higher than those of the control group (p<0.05). Angiotensin converting enzyme genotype frequencies in patients were observed as 28.2%, 18% and 53.8% for DD, II and ID polymorphism, respectively. These frequencies in controls were 42.5%, 20.5% and 37% for DD, II and ID, respectively. Serum angiotensin converting enzyme activities in both groups with II genotype were significantly lower than those with ID and DD genotype (p<0.05). Although conflicting results have been reported about this polymorphism in patients with peripheral vascular disease, we suggest that the angiotensin converting enzyme ID genotype may be a risk factor for peripheral vascular disease.
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PMID:ACE gene polymorphism in peripheral vascular disease. 1761 9

Diabetes mellitus is commonly associated with both microvascular and macrovascular complications (coronary artery disease, cerebrovascular events, severe peripheral vascular disease, nephropathy and retinopathy). There is wide evidence demonstrating that platelet degranulation and synthesis of TxA2 are increased in diabetic patients. For this reason, many studies on anti-platelet therapy have been made to reduce thrombotic complication of diabetes mellitus. Some diabetic patients, although treated with ASA, have a high prevalence of recurrent thrombotic events, which may presumably be due to an "ASA resistance". Nevertheless, this drug remains the one with the greatest benefit. To optimize its function, we should try to understand the causes of "aspirin resistance", try to find the most suitable dosage, recommending patients to comply constantly with the prescription given and to avoid interactions with other drugs. "Clopidogrel resistance" is a term not clearly defined. The clinical implications of "clopidogrel resistance" are unknown. An important consideration affecting the use of aspirin in diabetic patients is its interaction with ACE-inhibitors. Another question is antiplatelet therapy in nephropathic diabetic patients. Although these patients are at high thrombotic and haemorrhagic risk, they should nevertheless be considered eligible to undergo antithrombotic therapy, taking into account the individual's haemorrhagic risk.
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PMID:Diabetes, vascular complications and antiplatelet therapy: open problems. 1904 81

Systemic sclerosis (SSc) is a chronic autoimmune disease with clinical manifestations resulting from immune activation, fibrosis development, and damage of small blood vessels. Our aim was to critically illustrate the available data on the new treatments proposed for SSc to provide a clinically oriented overview of the current evidence. PubMed was used for literature search using "scleroderma" and "therapy" to identify all articles published on indexed journals between 1972 and 2008. The search was limited to publications in English and produced a total of 3,441 references, which included 735 review articles. These citations were then screened for articles dealing with the most recent therapy options for SSc, and 214 articles were selected for evaluation and discussion. Methotrexate, cyclophosphamide, calcium channel blockers, angiotensin converting enzyme inhibitors, prostacyclin analogues, D-penicillamine, and extracorporeal photopheresis are the most widely studied treatments for SSc and were considered as practiced treatments. Other therapeutic approaches have been developed more recently and include endothelin receptor antagonists and phosphodiesterase-5 inhibitors for pulmonary arterial hypertension and peripheral vascular disease. High-dose immunosuppression and stem cell transplantation constitute a promising treatment and data from randomized controlled trials are awaited. Intravenous gamma globulins, mycophenolate mophetil, collagen tolerance induction, rituximab, fluoxetine, pirfenidone, relaxin, halofuginone, anti-TGF-beta antibodies, and tyrosine kinase inhibitors awaits more solid data. The clinical management of patients with SSc remains a challenge and currently involves practiced and newly proposed therapeutic approaches. The disease pleiomorphism poses numerous difficulties to determine ideal outcomes to be used in clinical trials.
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PMID:Recent advances in the treatment of systemic sclerosis. 1913 59

NICE has updated its guideline on heart failure. The principal changes from the 2003 guideline include more directive advice on how to improve the quality and timeliness of diagnosis. There is greater encouragement to use beta-blockers, more emphasis on rehabilitation, and better access to specialist advice--particularly at the time of diagnosis, admission to hospital, and where symptoms do not respond to first-line therapy with diuretics, ACE inhibitors and beta-blockers. A full history should be taken and clinical examination carried out. Patients with a past history of MI, or those with a high plasma BNP, should be referred to be seen within two weeks for echocardiography and specialist opinion. The specialist should determine: whether heart failure is present; its likely aetiology; precipitating factors; type of cardiac dysfunction; correctable causes; relevant comorbidity, and prognosis. Those with no history of MI but an elevated plasma BNP should be referred to be seen within six weeks for such assessment. Older adults, and patients with peripheral vascular disease, erectile dysfunction, diabetes mellitus, interstitial pulmonary disease and COPD without reversibility should be considered for beta-blocker therapy. A start low, go slow approach is recommended, with clinical review after each titration. Monitoring should include a clinical assessment, medication review, and a check of renal function as a minimum. Such a review should take place at least six monthly but may have to be much more frequent if there is a change in drug prescription or clinical status. Patients with stable heart failure should be offered a supervised group exercise-based rehabilitation programme designed for such patients. This should include a psychological and educational component, and could be incorporated within an existing cardiac rehabilitation programme.
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PMID:Improving the management of chronic heart failure. 2116 97


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