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)

Although the risk for coronary heart disease (CHD) associated with single SNPs is modest it has been suggested that, in combination, several common risk-associated alleles could lead to a substantially better heart disease risk prediction. We have modelled this using 10 SNPs in ten candidate genes (APOB, NOS3, APOE, ACE, SERPINE1, MTHFR, ITGA2B, PON 1, LPL, and CETP) and their predicted summary risk estimates from meta-analysis. Based on published allele frequencies, approximately 29% of the general population would be expected to carry less than three risk alleles, approximately 55% would carry 3 or 4 risk alleles, 4% would have 6 and 1% 7 or more risk alleles. Compared to the mean of those with 3 or 4 risk associated genotypes, those with 6 and 7-or-more alleles have a significantly higher risk odds ratio (OR) of CHD (mean OR (95% Confidence Intervals), 1.70 (1.14 to 2.55); and 4.51 (2.89 to 7.04) respectively), while compared to those in the lowest decile of risk, those in the highest decile have a CHD odds ratio in the range of 3.05 (2.24 to 4.14). Taking into account age and the risk alleles carried, the mean 10 year probability for developing CHD for a 55 year old man was calculated to be 15% (8.6% to 24.8%), with nearly 1 in 5 having more than 20% risk. Whether this particular group of 10 SNPs will improve the accuracy of CHD predictions over the combination of classical risk factors in clinical use requires further experimental evidence.
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PMID:The use of meta-analysis risk estimates for candidate genes in combination to predict coronary heart disease risk. 1740 27

Acute coronary syndromes (ACS) present a major health challenge in modern medicine. With new clinical trials being conducted, our knowledge of latest therapies for ACS continually evolves. In this article, we review currently available medical therapies and provide evidence-based rationale for current pharmacologic therapies. Among the antiplatelet therapies, aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors demonstrate significant efficacy in reducing morbidity and mortality. Among the anticoagulants, unfractionated heparin and low molecular weight heparin, particularly enoxaparin sodium, remain the hallmarks of therapy against which newer anticoagulants are often compared. Bivalirudin has recently showed significant efficacy in decreasing cardiovascular events and mortality, but with potentially less risk of bleeding than heparin. Results of trials evaluating warfarin remain inconsistent regarding potential benefits. Finally, fondaparinux sodium, recently tested, shows promise as a powerful yet safe anticoagulant. Fibrinolysis is an acceptable modality for reperfusion if facilities equipped for primary percutaneous revascularization are not available. Regarding anti-ischemic therapy, beta-adrenoceptor antagonists and nitrates remain critical in the early management of ACS. Inhibitors of the renin-angiotensin-aldosterone system have also shown significant reductions in the morbidity and mortality of patients presenting with ACS, particularly in patients with left ventricular dysfunction and clinical heart failure, with ACE inhibitors being first-line agents and angiotensin receptor antagonists being a reasonable substitute if ACE inhibitors are not tolerated. Among the lipid-lowering therapies, statins (HMG-CoA reductase inhibitors) have been documented as being the most well tolerated and most efficacious therapies for ACS patients and data exist that they should be administered early in ACS management. Studies evaluating combination therapy (antiplatelet drugs, beta-adrenoceptor antagonists, ACE inhibitors, and lipid-lowering agents) show a clear benefit in mortality in patients with known coronary artery disease. Efforts to improve these key evidence-based medical therapies are numerous and include such programs as the American College of Cardiology's Guidelines Applied in Practice, international patient registries such as the Global Registry of Acute Coronary Events, and studies such as CRUSADE. Finally, patients with diabetes mellitus pose a challenge to clinicians both in terms of their glycemic control and in their apparent relative resistance to antiplatelet therapy. Studies involving ACS patients suggest that stringent glycemic control may result in benefits in both morbidity and mortality.
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PMID:Evidence-based medical therapy of patients with acute coronary syndromes. 1750 81

Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses.
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PMID:Genetic polymorphisms for the study of multifactorial stroke. 1842 1

Aim of the study was to elucidate genetic markers associated with elevated risk of sudden cardiac death (SCD). We collected autopsy material during 1999 - 2001 in a process of forensic medical pathologo-anatomical examination of corpses of 182 men who had died suddenly in Octyabrsky district of Novosibirsk in the age of 25 - 64 years (mean age 53,6 +/- 7,9 years). We studied polymorphisms of the following genes: angiotensin converting enzyme - , glycoprotein IIb/IIIa - GPIIb/IIIa, alpha2b adrenoreceptor - ADRA2B, beta(1)-adrenoreceptor - ADRB1. Control comprised samples of population of men aged 25 - 35 and 55 - 64 years from the same district of Novosibirsk examined within framework of international WHO project MONICA. Comparison of frequencies of genotypes of polymorphism A1/A2 of GPIIb/IIIa gene in combined sample of population and group with SCD revealed in SCD group lowering of portion of A2/A2 homozygotes (5.0 and 1.2%, respectively, =0.029) and elevation of portion of A1/A2 heterozygotes (18.7 and 28.3%, respectively, =0.027). Odds ratio for a heterozygote to enter SCD group was 1.71 (95% confidence interval 1.0 to 2.77). Comparison of frequencies of genotypes and alleles of polymorphism A145G of ADRB1 gene in combined sample of population and group with SCD did not reveal any difference. Comparison of frequencies of polymorphism I/D of ACE gene in combined sample of population and group with SCD revealed significant lowering of frequencies of genotype I/I in SCD group (22.0 and 13.8%, respectively, p=0.033). There were no significant differences between SCD group and control in frequencies of studied polymorphism of alpha2b-adrenoreceptor gene.
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PMID:[Sudden cardiac death and polymorphism of genes-candidates of cardiovascular diseases]. 1946 19

Contrary to the decline in the prevalence of several risk factors such as hypertension, hypercholesterolemia and smoking, diabetes is an expanding health burden in the Western world. Because of the proatherosclerotic, proinflammatory, and prothrombotic states associated with diabetes, diabetic patients with acute coronary syndromes (ACS) are at high risk of subsequent cardiovascular events. However, they derive at the same time greater benefit from evidence-based therapy than the non-diabetic individuals. The two mainstays of acute ACS therapy for diabetic patients are an aggressive platelet inhibition and an early invasive strategy. Aspirin should be administered in all patients and prasugrel is to be considered superior to clopidogrel in this setting. While the use of glycoprotein IIb/IIIa receptor inhibitors in the diabetic ACS population has been associated with a mortality reduction, the role of these agents in the prasugrel era remains to be elucidated. Importantly, the aggressiveness of anti-thrombotic therapy should be balanced in each individual patient with the risk of bleeding. The benefit of early coronary angiography and, if needed, revascularization, in the setting of non-ST-segment elevation ACS is more pronounced in diabetic than in non-diabetic individuals. All patients, diabetics and non-diabetics, qualify for primary percutaneous coronary intervention (PCI) as the therapy of choice for ST-segment elevation myocardial infarction. In order to reduce hemorrhagic complications related to vascular access for PCI, the radial approach should be favored. Additional important secondary preventive measures include high-dose statin therapy, ACE-Inhibition/angiotensin II receptor blockade, and adequate glucose metabolism control. Despite the documented efficacy, diabetic patients with ACS receive evidence-based treatments less frequently than non-diabetic individuals.
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PMID:Diabetes and acute coronary syndrome. 2046 8

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in both men and women in the developed countries. Despite this fact, females are still under-represented in the majority of clinical trials. At the present time, only limited evidence is available with respect to the female-specific aspects of pathogenesis, management, and outcomes in acute coronary syndrome (ACS). Women less frequently undergo coronary intervention, and a lower proportion of women receive evidence-based pharmacotherapy, compared with men. It has been shown that women benefit from an invasive approach and coronary intervention in ACS as much as men, despite their advanced age and higher rate of bleeding complications. Also, administration of beta-blockers, ACE-inhibitors, and intensive statin therapy is associated with a comparable reduction of cardiovascular event rates in women and men. On the other hand, women may profit less than men from fibrinolytic or glycoprotein IIb/IIIa inhibitor therapy. Both sexes benefit equally from aspirin therapy, whereas contradictory data are available on the efficacy of clopidogrel in women. There is an urgent need for intensive research in the development of female-specific therapeutic strategy in ACS, even though the detailed mechanisms of sex differences are still unknown.
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PMID:Women and the management of acute coronary syndrome. 2288 99


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