Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 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

Clinical trials that evaluate more aggressive cholesterol reduction in a broader range of patients at high risk for coronary heart disease (CHD) are needed to fill gaps in our understanding of the impact of lipid-lowering therapy on risks for clinical events and mortality. This paper briefly reviews results from recent landmark studies that have evaluated the benefits of aggressive lipid-lowering therapy in patients with, or at risk for, CHD. The Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study demonstrated that aggressive treatment with atorvastatin was significantly more effective than less aggressive therapy with pravastatin in slowing the progression of atherosclerosis in patients with symptomatic CHD. Results from two large-scale clinical end-point trials, the Heart Protection Study (HPS) and the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA), have shown that aggressive lipid-lowering treatment in patients with relatively low baseline levels of low-density lipoprotein cholesterol (LDL-C) significantly reduces CHD risk. Taken together, the results of these landmark trials not only support aggressive lipid lowering in patients at risk for CHD, but also suggest that greater LDL-C reductions may improve outcomes across a wide range of patients.
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PMID:The importance of aggressive lipid management in patients at risk: evidence from recent clinical trials. 1523 86

Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. They can exert strong effects on the human body that may be beneficial for athletic performance. A review of the literature revealed that most laboratory studies did not investigate the actual doses of AAS currently abused in the field. Therefore, those studies may not reflect the actual (adverse) effects of steroids. The available scientific literature describes that short-term administration of these drugs by athletes can increase strength and bodyweight. Strength gains of about 5-20% of the initial strength and increments of 2-5 kg bodyweight, that may be attributed to an increase of the lean body mass, have been observed. A reduction of fat mass does not seem to occur. Although AAS administration may affect erythropoiesis and blood haemoglobin concentrations, no effect on endurance performance was observed. Little data about the effects of AAS on metabolic responses during exercise training and recovery are available and, therefore, do not allow firm conclusions. The main untoward effects of short- and long-term AAS abuse that male athletes most often self-report are an increase in sexual drive, the occurrence of acne vulgaris, increased body hair and increment of aggressive behaviour. AAS administration will disturb the regular endogenous production of testosterone and gonadotrophins that may persist for months after drug withdrawal. Cardiovascular risk factors may undergo deleterious alterations, including elevation of blood pressure and depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol levels. In echocardiographic studies in male athletes, AAS did not seem to affect cardiac structure and function, although in animal studies these drugs have been observed to exert hazardous effects on heart structure and function. In studies of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to be strongly affected by AAS. Generally, AAS seem to induce increments of aggression and hostility. Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose and drug dependent. AAS dependence or withdrawal effects (such as depression) seem to occur only in a small number of AAS users. Dissatisfaction with the body and low self-esteem may lead to the so-called 'reverse anorexia syndrome' that predisposes to the start of AAS use. Many other adverse effects have been associated with AAS misuse, including disturbance of endocrine and immune function, alterations of sebaceous system and skin, changes of haemostatic system and urogenital tract. One has to keep in mind that the scientific data may underestimate the actual untoward effects because of the relatively low doses administered in those studies, since they do not approximate doses used by illicit steroid users. The mechanism of action of AAS may differ between compounds because of variations in the steroid molecule and affinity to androgen receptors. Several pathways of action have been recognised. The enzyme 5-alpha-reductase seems to play an important role by converting AAS into dihydrotestosterone (androstanolone) that acts in the cell nucleus of target organs, such as male accessory glands, skin and prostate. Other mechanisms comprises mediation by the enzyme aromatase that converts AAS in female sex hormones (estradiol and estrone), antagonistic action to estrogens and a competitive antagonism to the glucocorticoid receptors. Furthermore, AAS stimulate erythropoietin synthesis and red cell production as well as bone formation but counteract bone breakdown. The effects on the cardiovascular system are proposed to be mediated by the occurrence of AAS-induced atherosclerosis (due to unfavourable influence on serum lipids and lipoproteins), thrombosis, vasospasm or direct injury to vessel walls, or may be ascribed to a combination of the different mechanisms. AAS-induced increment of muscle tissue can be attributed to hypertrophy and the formation of new muscle fibres, in which key roles are played by satellite cell number and ultrastructure, androgen receptors and myonuclei.
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PMID:Effects of androgenic-anabolic steroids in athletes. 1524 88

The prevalence of hypertension in pediatric patients with renal transplant (Tx) has not changed for the last three decades, remaining at 50-80%. Long-standing and uncontrolled hypertension is associated with the development of end-organ damage including allograft dysfunction, early cardiomyopathy and premature atherosclerosis. Aggressive treatment of elevated BP is an essential part of Tx care with the goal to delay graft failure and prevent the development of symptomatic cardiovascular disease in young recipients of renal Tx.
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PMID:Hypertension and end-organ damage in pediatric renal transplantation. 1526 68

Cardiovascular disease and its clinical sequelae remain the leading causes of morbidity and mortality in many regions of the world. Dyslipidemia is a critical risk factor to intercept in both the primary and secondary prevention of acute cardiovascular events. The prospective, placebo-controlled clinical trials conducted with statins over the course of the past 15 years have conclusively demonstrated that these drugs significantly reduce risk for fatal and nonfatal myocardial infarction, ischemic stroke, unstable angina, and frequency of myocardial ischemia, as well as cardiovascular and all-cause mortality. Of considerable interest is the fact that, even under the exquisitely controlled circumstances of a clinical trial, endpoint reductions in these trials typically occur in the range of 20% to 35%. Understandably, much attention is now being focused on deriving the pharmacologic means by which to further increase the magnitude of endpoint reduction. Epidemiologic investigation has demonstrated that the relationship between cholesterol and risk for atherosclerotic disease is a continuous one. Consequently, it is reasonable to assume that more aggressive reductions of low-density lipoprotein (LDL) cholesterol might result in even greater reductions of cardiovascular event rates and atheromatous plaque progression than heretofore observed. Two recent clinical trials, Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT), prospectively tested and confirmed the validity of more aggressive LDL cholesterol lowering in high-risk patients with established coronary artery disease.
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PMID:Low-density lipoprotein reduction in high-risk patients: how low do you go? 1529

With so many statins available for clinical use in coronary artery syndromes, there has been much discussion about which is the best. Two recent trials have compared the clinical outcomes of intensive lipid lowering with atorvastatin 80 mg/day and standard lowering with pravastatin 40 mg/day. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial, patients with acute coronary artery syndromes were enrolled, and pravastatin lowered the low-density lipoprotein (LDL)-cholesterol to 2.46 mmol/l, whereas atorvastatin lowered it to 1.60 mmol/l. Associated with this, there was a lower rate of clinical events (myocardial infarction, revascularisation) over 2 years with atorvastatin than pravastatin (22.4 versus 26.3%, respectively). The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial also enrolled patients requiring angiography, and pravastatin lowered the LDL-cholesterol to 2.84 mmol/l, whereas atorvastatin lowered the LDL-cholesterol to 2.04 mmol/l. In the REVERSAL trial, atheroma volume progressed with pravastatin by 2.7% whilst remaining stable in the atorvastatin group (-0.4%) over 18 months. Thus, atorvastatin 80 mg/day causes a greater reduction in LDL-cholesterol than pravastatin 40 mg/day, and this is associated with a reduced progression of atheroma and reduced clinical events. As a consequence of these findings, the National Cholesterol Education Programme and European guidelines for LDL-cholesterol levels should be lowered.
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PMID:Atorvastatin versus pravastatin: intensive versus moderate lipid lowering. 1500 10

We had in view the effect of the oxidative aggression as determinant factor in atherogenic process associated with degenerative psychoorganic disturbances. It was studied a group of old people distributed in two subgroups: a) 51 old people with atherosclerosis (AS) and b) 57 old people with atherosclerosis associated with degenerative psychoorganic disturbances determined by chronic ethylism. The results were compared to those of a 40 healthy adults group. Concomitantly, it were evaluated the supervened modifications in the antioxidant defense systems of the organism, by determining both of some nonenzymatic defense system components (reduced glutathione, ceruloplasmine and transferrin) and of some enzymatic defense system components (superoxide dismutase, catalase and glutathione peroxidase). The obtained results emphasize an important aggression exerted by the lipid peroxides against the old people organism, aggression that is amplified by the chronic ethylism with appearance of the degenerative psychoorganic disturbances. Generally, the antioxidant defense capacity of the old people organism is depressed, especially in the group with atherosclerosis associated with degenerative psychoorganic disturbances engendered by excessive and chronic alcohol intake.
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PMID:Oxidative aggression in atherosclerosis associated to degenerative psychoorganic disturbances. 1552 47

Inflammation has a fundamental role in mediating all stages of atherosclerotic disease. The key role of oxidation in linking lipids and inflammation to atherosclerosis is compelling and supported by experimental evidence. However, the relevance of the antioxidant hypothesis for the treatment of patients with atherosclerosis has not been definitively proven. Probucol has reduced post-percutaneous coronary intervention (PCI) restenosis and progression of carotid atherosclerosis in clinical trials. The antioxidant/vascular protectant AGI-1067 has also been effective at preventing atherosclerosis in all tested animal models. The nonintervened reference coronary segments of the PCI vessel demonstrated improvements with AGI-1067 in the Canadian Antioxidant Restenosis Trial-1 (CART-1), evidence supportive of a clinical effect on slowing atherosclerosis progression. Results of randomized trials with the "antioxidant" vitamins have been disappointing, but there are potentially important problems associated with their use, including their potential pro-oxidant effects. Two important trials that test the antioxidant/anti-inflammatory hypothesis are ongoing with AGI-1067: CART-2, which assesses its value for the reduction of both atherosclerosis progression in non-PCI vessels and post-PCI restenosis; and Aggressive Reduction of Inflammation Stops Events (ARISE), which is evaluating the effects of AGI-1067 on hard cardiovascular outcomes.
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PMID:Antioxidants and atherosclerosis: emerging drug therapies. 1568 6

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.
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PMID:Are Canadian guidelines for cholesterol lowering in high-risk patients optimal? 1568 8

Data from studies on the benefits of statins in coronary artery disease patients in preventing recurrent primary and secondary cardiac endpoints, as well as ischemic strokes, imply the potential value of statins in recurrent ischemic stroke prevention without coronary artery disease symptoms or, by extension, primary ischemic stroke prevention. However, data on the latter are lacking, although the ongoing Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study is designed to answer that question. Until these data become available, clinicians are justified in using statins to avert recurrent ischemic strokes due to atherosclerosis, especially if elevated total cholesterol, increased low-density lipoprotein cholesterol, and/or reduced high-density lipoprotein cholesterol, as specified in the National Cholesterol Education Program Third Adult Treatment Panel, are present. This article reviews the pathophysiology of atherosclerosis, particularly the major components of atheromas of cholesterol, smooth muscle cells, inflammation, "foam cells," and connective tissue elements. Emphasis is placed on the first three and the results of statin trials in coronary artery disease, as well as the beneficial pleiotrophic effects of statins in ischemic strokes.
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PMID:Statins and stroke prevention. 1597 25


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