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

Nephroangiosclerosis and nephrosclerosis are terms used to define the renal disease induced by essential hypertension. The predominant histologic changes occur in the preglomerular microvasculature. Epidemiological data about the risk of hypertensive patients from developing renal failure offer conflicting results. Nevertheless, renal vascular disease, including nephroangiosclerosis and/or ischemic nephropathy, appears to be an important cause of end-stage renal disease. Presumably, nephrosclerosis is the renal expression of systemic atherosclerosis: male sex, age > 55-60 years, black race, high serum cholesterol and/or uric acid levels, and coronary heart disease, peripheral artery disease, and/or cerebrovascular disease are common associations with the renal alteration. Treatment strategy should include an intensive blood pressure control, probably below 130/80 mmHg, together with antiplatelet and lipid-lowering agents when necessary. Although specific studies are lacking, ACE inhibitors and angiotensin II antagonists may offer additional benefits in slowing the renal disease progression.
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PMID:[Arterial hypertension and renal vascular disease: nephroangiosclerosis]. 1198 69

Endothelial production of nitric oxide (nitrogen monoxide, NO) has become a major research area in vascular biology. Some of the most important effects that NO exerts in the vascular wall are potentially vasoprotective, because these effects maintain important physiological functions such as vasodilation, anticoagulation, leucocyte adhesion, smooth muscle proliferation, and the antioxidative capacity. During the last 2 decades it has become apparent that a variety of diseases are associated with an impairment of endothelium-dependent NO activity. One of the major causes is believed to be an increased production of reactive oxygen species, in particular superoxide, which have been shown to interfere with many steps of the NO--cyclic guanosine monophosphate (cGMP) pathway. This phenomenon has been found in diverse conditions such as atherosclerosis, hypertension, diabetes, hypercholesterolemia, heart failure, and cigarette smoking. The aim of this review is to examine the cellular and molecular mechanisms whereby NO exerts potentially vasoprotective effects and to discuss pharmacologic approaches targeting the NO pathway in view of their potential to improve endothelial function and to reduce the progression of atherosclerotic vascular disease. We conclude that there is compelling evidence for vasoprotective actions of NO which are mediated by cGMP-dependent and cGMP-independent mechanisms. These effects may contribute to the beneficial effects of established drugs such as ACE inhibitors or statins. Unfortunately, clinical data on the effect of long-term treatment with nitrates on the progression of coronary artery disease are lacking. Finally, L-arginine or new activators of the NO pathway may become therapeutic options in the future.
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PMID:Vasoprotection by nitric oxide: mechanisms and therapeutic potential. 1212 64

Pathogenesis of the atherosclerotic process is deemed as multifactorial. To the most important risk factors, besides certain family predisposition, there belongs hypercholesterolemia, arterial hypertension, obesity, diabetes mellitus, smoking and others. In the last years there are more and more data about the role of inflammation and infection in the whole development of atherosclerosis. The witness for this hypothesis is the findings of high parameters of inflammation in involved vessels as well as in the blood of atherosclerosis suffering persons. Opinions about the inflammation theory appear from the 90th. Local sterile inflammation in the subendotelium of the middle and big arteries has been proved to consist of specific immune reaction (activation of the T-lymphocytes) as well as nonspecific characteristic by elevated monocytes in the artery wall during the whole process of atherogenesis. Inflammation in the plaque can trigger and hold several factors engaged in the atherosclerotic process, such as oxidized LDL cholesterol, elevated production of various superoxides, activated macrophages, activated T-lymphocytes, cytokines (IL-1, IL-6, interferon gamma) and lipoprotein Lp (a). In this inflammation process levels of CRP (acute phase protein), fibrinogen and erythrocyte sedimentation are elevated as a reaction of the organism to nonspecific chronic infections. Because of this it is thought that elevated fibrinogen and erythrocyte sedimentation are markers of the cardiovascular risk. Some papers deal with antiinflammatory effects of statins, because these lower CRP levels so they also lower atherosclerotic risk through not only lowering of cholesterol levels. Also asprine, as an antiinflammation agent, changing the CRP levels, would be of benefit for patients with vascular disease because its antiaggregation and antiinflammatory effects. ACE inhibitors are also antiinflamatory through blocking of tissue production of angiotensin II (artery wall and atherosclerotic plaque). Enzymatic inhibitors changing angiotensin can also have a partial antiinflammatory effect. The infection theory is supported also by tracing of some microorganisms in the atherosclerotic plaque or in the blood, as e.g. Helicobacter pylori or Chlamydia pneumoniae; to the autoimmune origin is indicated the presence of the specific immunity reaction against heat shock proteins (HSP) or oxidized LDL. This infection theory offers new therapy possibilities. Therefore eradication for example by antibiotics can lead to stabilization of the atherosclerotic plaque with positive consequences, as it was discovered by many studies.
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PMID:[The role of infection and inflammation in the pathogenesis of atherosclerosis]. 1219 10

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.
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PMID:[Treatment of hypertension in type 2 diabetes mellitus--2002 update]. 1223 35

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
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PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

Blood pressure levels are strongly predictive of the risks of first-ever and recurrent stroke. The benefits of blood pressure-lowering therapy for the prevention of fatal and non-fatal stroke in middle-aged individuals are well established. However, until recently, there has been uncertainty about the consistency of such benefits across different patient groups and in particular, for older people and in those with a history of stroke. This paper discusses the evidence surrounding the effectiveness of blood pressure-lowering therapy, specifically in older patients with a history of stroke, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). PROGRESS was a randomised, double-blind, placebo-controlled trial of 6105 individuals with a history of cerebrovascular disease recruited from 172 hospital outpatient clinics in ten countries. Participants (mean age 64 years; range 26-91 years) were randomly assigned to receive active treatment with an ACE inhibitor-based blood pressure-lowering regimen (perindopril) with or without addition of the diuretic indapamide, or matched placebo. At the end of follow up (mean of 4 years), active treatment reduced the incidence of total stroke by 28% (95% CI 17-38%) and the rate of major vascular events by 26% (95% CI 16-34%). Importantly, benefits of treatment were consistent across key patient subgroups, including those with and without hypertension, patients who were Asian and non-Asian, and for both ischaemic and haemorrhagic strokes subtypes. Current evidence is now strong for clinicians to consider blood pressure-lowering therapy as pivotal in the prevention of stroke, especially in patients with a known history of cerebrovascular disease (and vascular disease, in general), irrespective of blood pressure levels, as soon as patients are clinically stable after an acute stroke or other vascular event. Additional age-specific analyses of the PROGRESS data, together with those from other completed trials, will provide more reliable information about the size of the benefits of blood pressure-lowering therapy, specifically for different age groups, and particularly in the oldest old (those aged >80 years). In the meantime though, an ACE inhibitor plus diuretic treatment regimen that maximises the degree of blood pressure reduction has a good safety profile and is an effective treatment that should be considered in all patients with stroke, including the elderly.
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PMID:The Perindopril Protection Against Recurrent Stroke Study (PROGRESS): clinical implications for older patients with cerebrovascular disease. 1264 80

Sneddon's syndrome is a rare combination of generalised livedo reticularis and cerebrovascular accidents. Its clinical presentation varies widely and its aetiology is still not known. 60 to 80% of patients are female. First symptoms of the syndrome are mostly repetitive cerebral strokes, but reduced perfusion of the skin, seen as blue or red-brown mottling, precedes the strokes. The vascular disease is generalised and often accompanied by arteriosclerosis, systemic arterial hypertension, valvular heart disease and the presence of antiphospholipid antibodies. The diagnostic procedures are complicated and have to exclude other autoimmunological diseases. Therapeutic options are anticoagulatory therapy with warfarin, ASS or heparin, reduction of endothelial proliferation with ACE-inhibitors, and improvement of microvascular perfusion with prostaglandine. The increased anaesthesiological risk with these patients is due to the acute risk of thromboembolism and ischaemic cerebral and cardiovascular insults. The anaesthetic management must provide stable perfusion pressures for cerebral and myocardial arteries and avoid increasing risk factors for thromboembolism such as increased blood viscosity or stasis due to improper positioning of the patient. The choice of anaesthetic drugs is dependent on good controllability for haemodynamic stability. The high risk of patients with Sneddon's syndrome justifies a more invasive haemodynamic monitoring and postoperative surveillance on an intensive care unit. This case report describes the anaesthesiological considerations for, and management of, a patient with Sneddon's syndrome who was admitted to hospital for vaginal hysterectomy.
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PMID:[Perioperative management of a patient with Sneddon syndrome--a case report]. 1287 40

Type 2 diabetes is characterised by insulin resistance in association with clustering of atherothrombotic risk factors (dysglycaemia, hyperinsulinaemia, hypertension, raised triglyceride, low HDL cholesterol and increased levels of plasminogen activator inhibitor-1 (PAI-1) and clotting factor VII). There is a 3-5 fold increase in risk of myocardial infarction rising to 10-20 fold in the presence of microalbuminuria and overall around 70-75% of subjects with type 2 diabetes die of cardiovascular disease. However, classical risk factors which associate with insulin resistance do not account for all the increased burden of vascular disease in diabetic subjects. Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow. Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein. In addition recent studies indicate that metformin has direct effects on fibrin structure/function and stabilises platelets, two important components of arterial thrombus. The United Kingdom Prospective Diabetes Study (UKPDS) reported that metformin was associated with a 32% reduction in any diabetes related endpoint (p<0.002), a 39% reduction in myocardial infarction (p<0.01) and a non-significant 29% fall in microvascular complications. The figures for macrovascular complications compare favourably for those described for other cardioprotective agents such as ACE inhibitors and statins. These findings confirm metformin as first line therapy in the management of obese insulin resistant type 2 diabetes and in the prevention of the vascular complications of this common condition.
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PMID:Beneficial effects of metformin on haemostasis and vascular function in man. 1450

Chymase is a chymotrypsin-like serine protease secreted from mast cells. Mammalian chymases are classified into two subgroups (alpha and beta) according to structure and substrate specificity; human chymase is an alpha-chymase. An important action of chymase is the ACE-independent conversion of Ang I to Ang II, but chymase also degrades the extracellular matrix, activates TGF-beta1 and IL-1beta, forms 31-amino acid endothelins and is involved in lipid metabolism. Under physiological conditions, the role of chymase in blood vessels is uncertain. In pathological situations, however, chymase may be important. In animal models of hypertension and atherosclerosis, chymase may be involved in lipid deposition and intimal and smooth muscle hyperplasia, at least in some vessels. In addition, chymase has pro-angiogenic properties. In human diseased blood vessels (e.g. atherosclerotic and aneurysmal aorta; remodeled pulmonary blood vessels), there are increases in chymase-containing mast cells and/or in chymase-dependent conversion of Ang I to Ang II. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of vascular disease. The effects of chymase can theoretically be attenuated either by reducing availability of the enzyme, with a mast cell stabiliser, or alternatively with specific chymase inhibitors. The mast cell stabiliser, tranilast, was shown to be beneficial in animal models of atherosclerosis, where a prevention protocol was used, but was not effective in clinical trials where it was administered after angioplasty. Chymase inhibitors could have the advantage of being effective even if used after injury. Several orally active inhibitors, including SUN-C8257, BCEAB, NK3201 and TEI-E548, are now available. These have yet to be tested in humans, but promising results have been obtained in animal models of atherosclerosis and angiogenesis. It is concluded that orally active inhibitors of chymase may have a place in the treatment of vascular diseases where injury-induced mast cell degranulation contributes to the pathology.
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PMID:Vascular chymase: pathophysiological role and therapeutic potential of inhibition. 1498 62

The encouraging results of recent multicenter clinical trials conducted in the US on the effect of carvedilol therapy in patients with chronic heart failure, prompted us to verify its tolerability in a group of elderly patients. For the open, randomized, placebo-controlled study, we selected 40 patients (28 men and 12 women, mean age 76.8+/-5.9 years) with mild, moderate or severe chronic heart failure. Exclusion criteria included dementia, chronic hepatitis, renal failure, severe vascular disease and respiratory failure. All patients were receiving treatment with digitalis, furosemide and ACE inhibitors. The study lasted 12 weeks. During the first week, all subjects received oral placebo or carvedilol, at a dose of 6.25 mg twice daily. The twice daily dose was then increased to 12.5 mg during weeks 2-4 and to 25 mg from weeks 5-12. At 0, after the 2 weeks of run-in, 4 and 12 weeks patients underwent assessment of systolic and diastolic blood pressure, heart rate, left ventricular ejection fraction, cognitive status and functional ability. Our findings indicate that elderly patients with congestive heart failure tolerate carvedilol therapy well. Carvedilol slightly improves heart function without altering functional or cognitive ability. A larger-scale trial in geriatric patients is now required to determine whether this treatment will reduce serious morbidity or mortality from heart failure.
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PMID:Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial. 1537 60


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