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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus and impaired glucose tolerance (IGT) are common disorders, and their prevalence is predicted to increase over the next several decades. The major serious complication of these disorders is large vessel atherosclerosis leading to myocardial infarction and stroke. Aggressive control of hypertension and dyslipidemia can significantly reduce risk for cardiovascular events, but a large amount of residual cardiovascular disease remains. A major remaining question is the potential role of aggressive glucose control for reducing macrovascular event rates in patients with diabetes. An ongoing trial addresses this issue, and a large number of other concurrent trials address several novel therapeutic strategies to reduce further the cardiovascular complications of diabetes or IGT. Many of these strategies test approaches that may directly target the vessel wall. Therapeutic modalities currently being evaluated include thiazolidinediones, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. Most of these trials will report their findings in the next 5 years. It is likely that the results of ongoing trials will significantly improve our approach to managing cardiovascular risk in patients with diabetes and IGT.
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PMID:Strategies in ongoing clinical trials to reduce cardiovascular disease in patients with diabetes mellitus and insulin resistance. 1517 14

The reduction of cardiovascular disease risk in kidney failure involves treatment of modifiable risk factors and provision of proven interventions to patients with established disease. Volume status management is key to blood pressure control. Statins are the agents of choice for the treatment of dyslipidemia. Target hemoglobin levels should be achieved using intravenous iron and erythropoietic agents. Combinations of calcium and noncalcium-containing phosphorus binders and vitamin D and its analogues should be used to attain target parathyroid hormone, phosphorus, and calcium phosphorus product levels. beta Blockers and aspirin are recommended in patients with ischemic heart disease and angiotensin-converting enzyme inhibitors (or angiotensin II receptor blockers), and beta blockers are recommended in patients with heart failure with reduced ejection fraction. In patients who require revascularization, studies suggest a survival benefit of coronary artery bypass graft surgery over percutaneous transluminal coronary angioplasty and coronary artery stenting.
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PMID:Treating the Patient with Kidney Failure to Reduce Cardiovascular Disease Risk. 1521 21

Chronic allograft nephropathy is a devastating complication of kidney transplantation that is responsible for a significant proportion of graft loss. This complication is characterized by a progressive decline in kidney function, which is not attributable to a specific cause. Many risk factors exist for the development of chronic allograft nephropathy, including donor-, recipient-, and transplant-related factors (eg, use of calcineurin inhibitors and acute rejection episodes), as well as comorbid conditions such as hypertension and hyperlipidemia. There is no definitive treatment for this complication; management has focused on minimization or withdrawal of calcineurin inhibitors in conjunction with addition of sirolimus or mycophenolate mofetil. Alterations in the immunosuppressive regimen must be done cautiously, as precipitating acute rejection will cause further damage to the allograft. Optimal control of blood pressure, particularly with the use of agents such as angiotensin II receptor blockers, in conjunction with management of dyslipidemia may be effective concurrent therapies in patients with chronic allograft nephropathy.
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PMID:Chronic allograft nephropathy: pathogenesis and management of an important posttransplant complication. 1526 52

Overweight/obesity represent an underestimated risk factor of renal disease. The incidence of obesity-related glomerulopathy (ORG) tremendously increased within the last decade. The first sign of renal damage in overweight conditions is microalbuminuria or proteinuria, indicating the potential risk of its progression to renal insufficiency and the development of premature cardiovascular events. In the early stage of obesity renal hemodynamics are characterized by a renal hypercirculation and glomerular hyperfiltration, particularly in the presence of hypertension. The hyperfiltration is especially harmful in patients with pre-existing inflammatory and metabolic renal disease, or under the conditions of reduced renal mass. Histopathologically, ORG is characterized by glomerulomegaly with/without signs of focal segmental glomerulosclerosis. Pathogenetically, numerous factors are involved, e.g. enhanced glomerular capillary pressure, adrenergic nerve overactivity, inappropriate activation of the renin-angiotensin-aldosterone system, insulin resistance, hyperinsulinemia and hyperleptinemia, dyslipidemia, enhanced clotting tendency and sodium retention. Diabetic nephropathy is one of the most serious complications of obesity-induced diabetes. In the industrial nations type 2 diabetes is the single most frequent cause of end-stage renal disease. After kidney transplantation, overweight/obesity is associated with a less favourable prognosis for the survival of the graft and the patient. Incidence of renal cell carcinomas is enhanced in overweight/obesity. Obesity-related renal disease may be prevented/postponed by an early weight reduction, by dietary intervention combined with physical exercise. In the advanced stages of renal disease benefits of weight reduction are minimal. Concomitant administration of angiotensin-converting-enzyme inhibitors or angiotensin II receptor 1 blockers exerts antiproteinuric effects and thereby aid in retarding the disease progression. Aimed prevention and treatment of obesity represent a challenge for the healthcare system. The concerted action of physicians, patients and the public health authorities is needed.
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PMID:[Overweight and obesity--risk factors in the development and progression of renal disease]. 1532 63

Conventional risk factors associated with cardiovascular and renal complications of diabetes include hypertension, dyslipidemia, hyperglycemia, and smoking. Recently, albuminuria has also emerged as an important risk factor, as it is independently associated with increased cardiovascular and renal risk. Inhibition of the renin-angiotensin-aldosterone system (RAAS) reduces both blood pressure (BP) and albuminuria, and induced cardiovascular and renal protection is associated with this albuminuria reduction, independent of BP reduction. Based on these results, optimal therapy for patients at risk for type 2 diabetic nephropathy should include BP reduction to <130/80 mm Hg, with the inclusion of a RAAS blocking agent (ie, an angiotensin II receptor blocker) to provide BP control and control of urinary albumin, which should be reduced to <500 mg/d.
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PMID:Should albuminuria be a therapeutic target in patients with hypertension and diabetes? 1553 5

Observational studies in different populations indicate a positive relationship between dyslipidemia, cardiovascular events, and kidney disease progression. Patients with chronic renal diseases usually present with conditions (inflammation, oxidative stress) that can induce quantitative and qualitative changes in lipoprotein composition, making these particles more atherogenic. Several large randomized trials have shown that lowering cholesterol with statins reduces coronary mortality and morbidity across a wide range of cholesterol levels. Moreover, statins ameliorated renal function and structure in experimental models of progressive renal disease as well as in patients with proteinuric disease. It has been hypothesized that statins may directly modulate intracellular signaling systems involved in cellular proliferation, inflammatory, and fibrogenic responses. In addition, studies in animals have shown that the mevalonate pathway also may be involved in the regulation of the renin-angiotensin system, providing the rationale for the use of statins in combination with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor antagonists, 2 classes of drugs that have evidenced beneficial effects in different forms of renal diseases. Preliminary studies have shown that a multidrug approach may induce remission of proteinuria, lessen renal injury, and protect from loss of function in those patients whose condition does not fully respond to a single treatment.
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PMID:Lipid oxidative stress and the anti-inflammatory properties of statins and ACE inhibitors. 1564 11

The metabolic syndrome is a worldwide epidemic, setting the stage for type 2 diabetes and its microvascular complications, and acceleration of macrovascular disease. Insulin resistance, hyperglycemia, dyslipidemia, hypertension, thrombotic disorders and adiposity define the metabolic syndrome and contribute to endothelial dysfunction and, subsequently, to accelerated atherosclerosis. Angiotensin II contributes to the development and progression of cardiovascular and renal endpoints and, as such, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors demonstrate a protective effect. Ligands for the peroxisome proliferator-activated receptor gamma (PPAR gamma), appear to impact favourably on atherosclerosis through both direct and indirect mechanisms. In humans, these ligands improve endothelial function, attenuate albuminuria and hypertension, and potentially prevent conversion of prediabetes to type 2 diabetes. Statins also have proven benefit in decreasing overall cardiovascular and stroke mortality and morbidity. The combination of angiotensin II blockade, statin therapy and PPAR gamma activation might emerge as an important global therapeutic strategy in the metabolic syndrome and diabetes. Further studies are needed to determine whether they have synergistic effects to protect the vasculature.
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PMID:Metabolic syndrome-interdependence of the cardiovascular and metabolic pathways. 1578 Aug 21

Cardiac artery disease and heart failure are major causes for morbidity and mortality in diabetes in general and in those with chronic kidney disease (CKD) in particular. Hypertension and dyslipidemia are more common in diabetes and the prevalence of coronary artery disease in diabetics is two-fold to four-fold higher than in nondiabetics. In those with CKD the incidence of cardiovascular complications is nearly two-fold higher than those without CKD. Recent studies suggest that the pathophysiology of cardiac disease is complex process involving both microvascular and macrovascular disease. In addition, myocardial lipotoxicity may be a novel contributing factor particularly in type 2 diabetics. Compelling evidence from cardiovascular outcomes trials indicates that treatment with drugs that block the renin-angiotensin system are cardioprotective in diabetics with microalbuminuria and early stages of kidney disease. Multiple risk factor intervention aimed at optimal blood pressure control (BP <130/<80 mmHG), lowering LDL cholesterol below 100 mg/dl, lowering triglyceride level to 150 mg/dl, A1C <6.5%, treatment with an ACE inhibitor or an angiotensin II receptor blocker, administration of once daily low-dose aspirin and smoking cessation together reduce cardiovascular morbidity and mortality in type 2 diabetics. Novel studies including diabetics with nephropathy aimed at improving outcomes in diabetics by treatment of anemia and optimal control of dyslipidemia are now underway. These and other clinical trials should provide important new insights into improving the quality of life in diabetics and ultimately preventing cardiac disease.
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PMID:Heart disease in diabetic patients. 1629 58

The renin-angiotensin-aldosterone system (RAAS) is a well known regulator of blood pressure (BP) and determinant of target-organ damage. It controls fluid and electrolyte balance through coordinated effects on the heart, blood vessels, and Kidneys. Angiotensin II (AII) is the main effector of the RAAS and exerts its vasoconstrictor effect predominantly on the postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and the ultrafiltration of plasma proteins, effects that may contribute to the onset and progression of chronic renal damage. AII may also directly contribute to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. Interventions that inhibit the activity of the RAAS are renoprotective and may slow or even halt the progression of chronic nephropathies. ACE inhibitors and angiotensin II receptor antagonists can be used in combination to maximize RAAS inhibition and more effectively reduce proteinuria and GFR decline in diabetic and nondiabetic renal disease. Recent evidence suggests that add-on therapy with an aldosterone antagonist may further increase renoprotection, but may also enhance the risk hyperkalemia. Maximized RAAS inhibition, combined with intensified blood pressure control (and metabolic control in diabetics) and amelioration of dyslipidemia in a multimodal approach including lifestyle modifications (Remission Clinic), may achieve remission of proteinuria and renal function stabilization in a substantial proportion of patients with proteinuric renal disease. Ongoing studies will tell whether novel drugs inhibiting the RAAS, such as the renin inhibitors or the vasopeptidase inhibitors, may offer additional benefits to those who do not respond, or only partially respond, to this multimodal regimen.
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PMID:The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. 1633 78

While diabetes mellitus is most often associated with hypertension, dyslipidemia, and obesity, these factors do not fully account for the increased burden of cardiovascular disease in patients with the disease. This strengthens the need for comprehensive studies investigating the underlying mechanisms mediating diabetic cardiovascular disease and, more specifically, diabetes-associated atherosclerosis. In addition to the recognized metabolic abnormalities associated with diabetes mellitus, upregulation of putative pathological pathways such as advanced glycation end products, the renin-angiotensin system, oxidative stress, and increased expression of growth factors and cytokines have been shown to play a causal role in atherosclerotic plaque formation and may explain the increased risk of macrovascular complications. This review discusses the methods used to assess the development of atherosclerosis in the clinic as well as addressing novel biomarkers of atherosclerosis, such as low-density lipoprotein receptor-1. Experimental models of diabetes-associated atherosclerosis are discussed, such as the streptozocin-induced diabetic apolipoprotein E knockout mouse. Results of major clinical trials with inhibitors of putative atherosclerotic pathways are presented. Other topics covered include the role of HMG-CoA reductase inhibitors and fibric acid derivatives with respect to their lipid-altering ability, as well as their emerging pleiotropic anti-atherogenic actions; the effect of inhibiting the renin-angiotensin system by either ACE inhibition or angiotensin II receptor antagonism; the effect of glycemic control and, in particular, the promising role of thiazolidinediones with respect to their direct anti-atherogenic actions; and newly emerging mediators of diabetes-associated atherosclerosis, such as advanced glycation end products, vascular endothelial growth factor and platelet-derived growth factor. Overall, this review aims to highlight the observation that various pathways, both independently and in concert, appear to contribute toward the pathology of diabetes-associated atherosclerosis. Furthermore, it reflects the need for combination therapy to combat this disease.
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PMID:Diabetes mellitus-associated atherosclerosis: mechanisms involved and potential for pharmacological invention. 1648 46


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