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

Much debate surrounds the question of the optimal therapeutic choices for medication to control blood pressure and reduce cardiovascular events. Experimental evidence suggests that drugs that block the renin-angiotensin system retard vascular disease through their direct ability to antagonize the effects of angiotensin II, which has vasoconstrictive, vascular proliferative, and atherosclerotic effects. It is not known how to separate the potential vascular protective effects of the drugs from their antihypertensive benefits. Clinical trial evidence indicates that achieved lower blood pressure goals almost always confer cardiovascular risk reduction advantages. There is also evidence, however, that successful antihypertensive regimens incorporating a renin-angiotensin system blocker, such as an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, provide more cardiovascular risk reduction benefit compared with regimens that do not incorporate a renin-angiotensin blocker. This includes composite or specific end points involving reduction of stroke, myocardial infarction, or development of end-stage renal disease.
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PMID:Providing end-organ protection with renin-angiotensin system inhibition: the evidence so far. 1647 78

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

The role of angiotensin II, the key mediator of the renin-angiotensin-aldosterone system, in the pathophysiology of cardiovascular disease is well known. Pharmacologic interruption of the activity of angiotensin II, either through blockade of the angiotensin receptor or inhibition of angiotensin-converting enzyme, is associated with a reduction in cardiovascular disease morbidity and mortality, as evidenced by accumulated data from large-scale, well-controlled clinical trials in high-risk populations. As the underlying mechanisms of vascular disease and the effects of blockade of the renin-angiotensin-aldosterone system on these processes have been further defined, the therapeutic focus has begun to shift toward prevention of disease progression at earlier stages. Continued research has identified early signs of vascular disease, such as endothelial dysfunction and vascular and cardiac remodeling, which occur long before clinical manifestations of cardiovascular disease become evident. Diagnostic tests are now available to assess otherwise healthy individuals for these signs. A preliminary trial is under way to evaluate the role of angiotensin receptor blockade as preventive treatment of individuals with early signs of vascular or cardiac disease.
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PMID:What is the role of angiotensin-receptor blockade in cardiovascular protection? 1707 Jan 45

The increasing prevalence and costs of type 2 diabetes mellitus (DM) make strategies to prevent its development vitally important. This analysis was conducted to determine if angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevent the development of DM. Medline and the Cochrane Central Register of Controlled Trials (1966 to May 2006) were queried for prospective, randomized, placebo-controlled or active-controlled trials of ACE inhibitor or ARB therapy in adults that reported rates of new-onset diabetes during follow-up. Meta-analyses of summary statistics from individual trials were performed using a random-effects model. Thirteen trials with a total of 93,451 patients were identified. Renin-angiotensin system antagonists reduced the incidence of DM from 9% in nontreated patients to 7.1% in those treated, a 26% reduction in odds (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.66 to 0.81, p<0.001). The effect sizes were similar in trials that randomized only hypertensive subjects (OR 0.73, 95% CI 0.66 to 0.82, p<0.001) and trials that studied the impact of renin-angiotensin system inhibition on outcomes of patients with vascular disease or heart failure (OR 0.67, 95% CI 0.50 to 0.90, p=0.008). ACE inhibitors and ARBs had comparable effects on the development of DM. In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p<0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p<0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM.
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PMID:Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials). 1739 2

In the United States, 18 million adults have diabetes and an additional 16 million have impaired glucose tolerance. Of these patients, 75% will die of some form of heart or vascular disease. Furthermore, recent data suggest that even prediabetic patients are at increased risk for cardiovascular (CV) events. Patients with diabetes often have multiple comorbid CV risk factors (e.g., dyslipidemia, hypertension, hyperglycemia) that synergistically interact to accelerate the pathogenesis of CV disease and dramatically increase the risk for CV events. For example, compared with patients without diabetes, patients with diabetes have a 3- to 5-fold increased risk of death due to congestive heart disease at every cholesterol level and are at increased risk for hypertension and hypertension-related CV events. Patients with diabetes are likely to benefit from intensive therapy incorporating multiple CV risk-reduction strategies. Lipid-modification--primarily reducing levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides and increasing high-density lipoprotein cholesterol (HDL-C) through pharmacologic and lifestyle intervention--is an integral part of such therapy. Patients with diabetes will also benefit from intensive blood pressure-lowering therapy with multiple classes of antihypertensives including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in particular, as well as concomitant antiplatelet therapy. An intensive risk-reduction approach combining these treatments would dramatically reduce the incidence of CV morbidity and mortality in this high-risk patient population.
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PMID:The patient with diabetes: preventing cardiovascular complications. 1743 22

Patients with hypertension, particularly those with diabetes mellitus, are at heightened risk for cardiovascular and renal disease. Accumulated evidence indicates that the majority of hypertensive patients at high risk will require more than one antihypertensive agent to reach their blood pressure (BP) target. A reasonable strategy is to use agents with complementary mechanisms of action to enhance BP-lowering efficacy and prevent target organ damage. In experimental models, the combination of a calcium channel blocker (CCB) with an agent that blocks the renin-angiotensin system (RAS), an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, improves measures of endothelial function, inflammation, ventricular remodelling and renal function to a greater degree than these classes given as monotherapy. In clinical trials, calcium channel/RAS blockade combination therapy has been shown to provide greater BP reductions and improve renal function in patients with diabetic and nondiabetic renal disease earlier and to a greater extent than monotherapy. In addition, dual calcium channel/RAS blockade increases arterial compliance, arterial distensibility and flow-mediated vasodilation. Expanding upon extensive research on the benefits of calcium channel blockade and RAS blockade for the prevention of vascular events and preclinical and clinical trial evidence suggests added effects of combination therapy by targeting the underlying mechanisms of hypertensive vascular disease.
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PMID:Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin-angiotensin system blockade. 1759

(1) Scleroderma and secondary Raynaud's phenomenon are frequently associated with increased morbidity for which no specific standardised treatment guidelines exist. (2) Current therapies for scleroderma target the immune system, with the goal of reducing inflammation and secondary tissue injury and fibrosis. Therapy targeting underlying vascular disease is designed to improve the symptoms of Raynaud's phenomenon and to reduce ischemic injury to involved organs. (3) Few controlled trials of therapy used for scleroderma are completed, and current treatments are largely based on organ-specific therapy and uncontrolled case series suggesting disease modification. (4) Recent randomised, controlled trials in scleroderma demonstrate promising results in the treatment of interstitial lung disease with cyclophosphamide, and vascular disease of the lungs and digits with endothelin receptor antagonists, the phosphodiesterase inhibitor sildenafil and prostacyclins, while trials with methotrexate show only modest benefit in controlling scleroderma-associated skin disease. (5) Prostacyclins are a therapeutic option in patients with secondary Raynaud's phenomenon. Modest benefits have also been shown with alpha1-antagonists and calcium channel blockers, while the effect of ACE inhibitors has been variable. Some data suggest some benefits to the use of the phosphodiesterase inhibitor sildenafil, the serotonin uptake inhibitor fluoxetine and the angiotensin receptor inhibitor losartan.
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PMID:Current drug therapy for scleroderma and secondary Raynaud's phenomenon: evidence-based review. 1791 43

The renin angiotensin system (RAAS) plays an important role in the pathophysiology of cardiovascular (CV) disease. Modulation of RAAS with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and aldosterone inhibitors reduces a range of adverse CV outcomes in patients with or at risk of CV disease. Currently, there is incomplete evidence to show all RAAS modulators provide vascular protection by reducing the incidence of myocardial infarction (MI), stroke and CV death. In patients at high risk for CV events, studies with ACEi designed to test for long-term vascular protection, showed benefit. In contrast, studies of ARBs in patients with hypertension, heart failure, and renal disease have not consistently shown a reduction of CV outcomes. However, none of these studies was specifically designed to examine the impact of ARBs on the vascular protective outcomes of CV death, non-fatal MI, and stroke. The ONTARGET and TRANSCEND studies are designed to determine whether the ARB telmisartan is similar (or non-inferior) or superior to the ACEi ramipril in the reduction of CV events in patients with established CV disease or diabetes with target organ damage. The ONTARGET study has enrolled 25,620, and TRANSCEND 5,776 subjects. The subjects in both trials are similar to those studied in the HOPE study, yet there is greater ethnic diversity, a higher proportion of patients with cerebro-vascular disease, and a greater use of beta blockers and lipid-lowering treatment. The studies completed recruitment in 2004, and are due to complete follow-up and report the results in 2008. The ONTARGET and TRANSCEND studies will provide valuable comparative data on the efficacy of telmisartan and ramipril and their combination in patients at high risk for CV events. Although it is possible that enhanced benefits will be observed with dual therapy, the outcomes with ARB monotherapy remain uncertain.
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PMID:Clinical trial update: focus on the ONTARGET study. 1820 Aug 9

This commentary discusses the findings and profound clinical implications of a prespecified analysis of renal outcomes performed by Mann et al. in the large ONTARGET study. This study assessed the effects of the angiotensin-converting-enzyme (ACE) inhibitor ramipril and the angiotensin receptor blocker (ARB) telmisartan, separately and in combination, in patients aged at least 55 years who had established vascular disease or diabetes with organ damage. Mann et al. demonstrated that, in contrast to monotherapy with either drug, the combination of an ACE inhibitor and an ARB worsens all major renal outcomes with the exception of proteinuria. This commentary recommends that combination therapy with an ACE inhibitor and an ARB to retard progression of renal disease should be avoided in patients with proteinuria lower than 1 g per day. The utility of dual RAS blockade regimens comprising an ACE inhibitor and a direct renin inhibitor, or an ACE inhibitor or ARB plus an aldosterone blocker, remains to be determined and constitutes a high priority subject for future clinical investigation.
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PMID:Re-examining RAS-blocking treatment regimens for abrogating progression of chronic kidney disease. 1870 86

It is now widely accepted that redox signaling is a key feature in vascular homeostasis. Reactive oxygen species are generated by a wide range of enzymatic systems located in both vascular endothelium and vascular wall. Further, to their role as cytotoxic molecules produced by immune system, free radicals play critical signaling roles in the vascular wall. By regulating several redox-sensitive transcription pathways, free radicals play a key role in the synthesis of inflammatory mediators in both vascular endothelium and vascular wall, with important role in the overall vascular dysfunction. The well-established role of redox state in vascular disease mandates that development of newer therapeutic strategies should be able to alter redox-sensitive intracellular signaling events. Widely used cardiovascular agents like statins or angiotensin receptor blockers have well documented beneficial effects on vascular redox state, reflected also in clinical outcome improvement. Newer promising strategies along with recent patented inventions may also include thiazolidinediones, folates, tetrahydrobiopterin, cyclopentone prostaglandins and aldose reductase inhibitors with well known effects on vascular redox, but with still unclear results on clinical outcome. Better understanding of redox-sensitive intracellular signaling pathways could indicate the critical steps to intervene with newer agents to reverse vascular dysfunction, inhibiting atherosclerosis progression and potentially improve clinical outcome.
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PMID:Novel therapeutic strategies targeting vascular redox in human atherosclerosis. 1951 50


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