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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular disease is a multifactorial disease that involves atherosclerotic and thrombotic factors. Genetic polymorphisms have been associated with myocardial infarction and angina pectoris. The aim of the present study was to assess the relationship between some genetic polymorphisms and myocardial infarction (MI) or vasospastic angina pectoris in a population from southern France. Genetic polymorphisms of the renin angiotensin system (the D/I polymorphism of the ACE gene and the A1166C polymorphism of the angiotensin II type 1 receptor [AT1R]) and of haemostatic factors (the -675 4G/5G polymorphism of the plasminogen-activator inhibitor 1[PAI-1] gene, and the G to T common point mutation in exon 2, codon 34 of the Factor XIII A-subunit gene) were examined. We assessed the genotype distribution in consecutive coronary artery disease (CAD) patients with MI (n = 201) and vasospastic angina pectoris (n = 43) and in 244 healthy controls comparable in age, sex, body mass index and total cholesterol level. The genotype distribution of AT1R polymorphism was significantly different between controls and patients, the prevalence of the C allele carriers being higher in patients with MI after the age of 45 than in control individuals (61 vs 45%, p <0.01), leading to an odds ratio (OR) of 2 (CI: 1.2-3.4). When looking at the group of patients with vasospastic angina the difference was even higher (76 vs 45%, p <0.01) yielding an OR of 4.3 (CI: 1.4-17.4). Genotype distributions of ACE, PAI-1 and Factor XIII polymorphisms were similar in patients and in controls. This study is in favor of a role of ATIR gene polymorphism in myocardial infarction and vasospastic angina.
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PMID:Genetic polymorphisms and coronary artery disease in the south of France. 1073 75

The results of the HOPE ("Heart Outcomes Prevention Evaluation") study, recently published in the New England Journal of Medicine, demonstrated a highly significant cardiovascular protection by an angiotensin converting enzyme inhibitor, ramipril at a dose of 10 mg/day, after a mean follow-up of 4.5 years, but not of vitamin E supplements at a dose of 400 UI/day in high-risk patients (> 55 years old) who had evidence of vascular disease (secondary prevention) or combined diabetes mellitus and another cardiovascular risk factor (primary prevention).
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PMID:[Clinical study of the month. The HOPE study, a two-by-two factorial clinical trial with contrasted results]. 1076 84

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. The endothelium controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium-derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been demonstrated in various vascular beds of different animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of endothelial dysfunction have been reported, including impaired signal transduction or substrate availibility, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium-derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycaemia-induced endothelial dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non-enzymatic glycation and oxidative stress. Correction of these pathways, as well as administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. Since the mechanisms of endothelial dysfunction appear to differ according to the diabetic model and the vascular bed under study, it is important to select clinically relevant models for future research of endothelial dysfunction.
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PMID:Endothelial dysfunction in diabetes. 1088 79

The development of new antihypertensive agents is becoming even more important. We need better blood pressure control and also agents that treat hypertension as a disease of the vascular endothelium. Recently, it has been shown that blocking the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors reduces blood pressure and decreases the incidence of vascular disease. Another peptide system, the natriuretic peptide system, has also been shown to be important in blood pressure control and volume homeostasis. Because ACE and neutral endopeptidase, the enzyme responsible for the degradation of the natriuretic peptides, are both zinc metalloproteases, new pharmaceuticals that inhibit both enzymes have been developed. The first of these, omapatrilat, has been shown to be an effective antihypertensive agent and to have great potential for treating congestive heart failure.
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PMID:Vasopeptidase inhibition: a new direction in cardiovascular treatment. 1098 Nov 74

Atherosclerotic renal artery stenosis typically occurs in high-risk patients with coexistent vascular disease elsewhere. Patients with atherosclerotic renal artery stenosis may develop progressive renal failure but have a much higher risk of dying of stroke or myocardial infarction than of progressing to endstage renal disease. Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or an increase in plasma creatinine levels during angiotensin converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive agents, statins, and aspirin is necessary in almost all cases.
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PMID:Atherosclerotic renal artery stenosis: surgery, percutaneous transluminal angioplasty, or medical therapy? 1099 25

Renal transplant recipients die of CVD at an accelerated rate compared with the general population. Successful management of CVD risk would prolong patient and renal allograft life, but management must begin early in the pretransplant period. By the time a renal transplant becomes available, patients often have advanced CVD because of prolonged and progressive renal disease. The most effective way to reduce premature CVD in renal transplant recipients is to address the problem of cardiac disease and vascular disease at the earliest stages in the natural history of progressive renal disease. Based largely on the success of such treatments in the general population, pretransplant modification may include the use of statins to control hyperlipidemia and ACE inhibitors to control elevated blood pressure. Elevated blood pressure has been related to the development of cardiomyopathy prior to transplantation; thus, therapeutic goals should be revised to include reversal of LVH. Longitudinal studies are needed to evaluate the effects of blood pressure lowering on LVH (and other echocardiographic abnormalities) in patients with progressive renal disease, patients on dialysis, and even following transplantation. Echocardiographic parameters have been shown to be stronger determinants of CVD mortality than conventional risk factors in the transplant population, and studies are needed to look at regression of these echocardiographic abnormalities with blood pressure control.
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PMID:Pretransplant management of end-stage renal disease patients to minimize posttransplant risk. 1115 31

National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC/AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basis for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal (i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension) (15). AT1 antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controlled studies with bisoprolol, carvedilol and metoprolol in addition to diuretics, digitalis and ACE inhibitors convincingly yielded positive results in chronic left ventricular failure patients. Reduction of mortality by 35% and even of sudden cardiac deaths by 40% have been proven beyond doubt. Thus, heart failure patients today should also receive beta-blocking agents in all stages of the disease. In the era of controlled prospective studies (evidence-based medicine), physicians are well advised to use only drugs that have been proven beneficial in large controlled studies.
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PMID:The management of heart failure--an overview. 1119 49

There is increasing evidence that direct pathobiological events in the vessel wall play an important role in vascular disease. An important mechanism involves the perturbation of the homeostatic balance between NO and reactive oxygen species. Increased reactive oxygen species can inactivate NO and produce peroxynitrite. Angiotensin II is a potent mediator of oxidative stress and stimulates the release of cytokines and the expression of leukocyte adhesion molecules that mediate vessel wall inflammation. Inflammatory cells release enzymes (including ACE) that generate angiotensin II. Thus, a local positive-feedback mechanism could be established in the vessel wall for oxidative stress, inflammation, and endothelial dysfunction. Angiotensin II also acts as a direct growth factor for vascular smooth muscle cells and can stimulate the local production of metalloproteinases and plasminogen activator inhibitor. Taken together, angiotensin II can promote vasoconstriction, inflammation, thrombosis, and vascular remodeling. In this article, we propose a model that unifies the interrelationship among cardiovascular risk factors, angiotensin II, and the pathobiological mechanisms contributing to cardiovascular disease. This model may also explain the beneficial effects of ACE inhibitors on cardiovascular events beyond blood pressure reduction.
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PMID:Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis. 1130 1

Atheromatous renovascular disease (ARVD) is a common cause of hypertension and chronic renal failure (CRF). In this unit, intravenous digital subtraction angiography (DSA) (or intraarterial DSA if indicated) is used as a screening angiographic study when ARVD is suspected. However, increased use of these investigations has resulted in a longer waiting time for angiography. As the majority of studies are negative for ARVD, clinical features and results of investigations of patients undergoing angiography were reviewed to identify those having the greatest likelihood of ARVD. The clinical notes were reviewed for all 249 patients undergoing angiography over an 18-month period. Primary indications for investigation were: hypertension 71 (28.5%), CRF 156 (62.7%) and CRF with severe hypertension 22 (8.8%). 12 of the CRF patients had end-stage renal failure. 166 (66.7%) patients had no evidence of ARVD, while only 83 (33.3%) patients showed some degree of ARVD, 29 (35%) of which had bilateral renal artery disease. There was no significant difference between the ARVD group and the non-ARVD group for mean age (69.0 years vs 63.3 years), male to female ratio, history of smoking (68.7% vs 55.4%), severe hypertension (10.8% vs 9.0%), hypercholesterolaemia (61.4% vs 47.0%), diabetes mellitus (28.6% vs 25.3%) or angiotensin converting enzyme inhibitor-related renal dysfunction (9.6% vs 6.1%). More patients in the ARVD group were investigated for CRF than in the non-ARVD group, as reflected by the higher serum creatinine level and the lower creatinine clearance in the ARVD group. 55 (33.1%) of the non-ARVD patients had no comorbid vascular disease, vascular bruits or ultrasound discrepancy in the size of the two kidneys, whereas all ARVD patients had at least one of these features (negative predictive value 100%). All three features were present in 19.3% of ARVD patients but in only 3.0% of the non-ARVD patients (positive predictive value 76.2%, specificity 97%). We plan to rationalize the criteria for angiography in the light of these findings, anticipating an increase in the diagnostic yield of renal angiography from its current 33.3% to above 42%.
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PMID:Increasing the diagnostic yield of renal angiography for the diagnosis of atheromatous renovascular disease. 1133 95

Although molecular cardiology is a relative young discipline, the impact of the new techniques on diagnosis and therapy in cardiovascular disease are extensive. Our insight into pathophysiological mechanisms is rapidly expanding and is changing our understanding of cardiovascular disease radically and irrevocably. Molecular cardiology has many different aspects. In this paper the importance of molecular cardiology and genetics for every day clinical practice are briefly outlined. It is expected that in the genetic predisposition for atherosclerotic disease multiple genes are involved (genetics). The role of only a minority of genes involved in the atherosclerotic process is known. Far less is known about particular gene-gene and gene-environment interactions. In some families disease can be explained mostly by a single, major gene (monogenic), of which the lipid disorder Familial Hypercholesterolemia is an example. In other cases, one or several variations in minor genes (multigenic) contribute to an atherosclerotic predisposition, for instance the lipoprotein lipase gene. Although mutations in this gene influence lipoprotein levels, disease development is predominantly depending on environmental influences. Recently several additional genetic risk factors were identified including elevated levels of lipoprotein (a) [Lp(a)], the DD genotype of angiotensin converting enzyme (ACE), and elevated levels of homocysteine. This illustrates the complexity of genetics in relation to atherosclerosis and the difficulty to assign predictive values to separate genetic risk factors. Furthermore, little attention has been given to protective genes thus far, explaining why some high risk patients are protected from vascular disease. Genetics based treatment or elimination of the genetic risk factor requires complete understanding of the pathogenic molecular basis. Once this requirement is fulfilled, disease management can be strived for, provided that adequate medical management is available. Recent studies suggest that such treatment should be genotype specific, as the genetic makeup can determine the outcome of a pharmacological intervention (pharmacogenetics). Once the trigger for atherosclerosis has initiated disease development, various genes are activated or silenced and contribute to lesion progression. Every stage of lesion development depends on a different gene expression programme (genomics). In this review paper an introduction is provided into genetics, pharmacogenetics and gene expression with respect to atherosclerotic disease.
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PMID:Molecular genetics and gene expression in atherosclerosis. 1157 98


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