UMLS:C0004153 - FACTA Search

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)

During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
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PMID:Pathophysiology of coronary artery disease. 1598 62

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.
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PMID:Quest for novel cardiovascular biomarkers by proteomic analysis. 1608 68

Inflammation is pivotal in atherosclerosis, and C-reactive protein (CRP) is an inflammatory marker that predicts cardiovascular events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial compared the standard lowering of low-density lipoprotein (LDL)-cholesterol with pravastatin 40 mg/day, with the intense lowering of LDL-cholesterol with atorvastatin 80 mg/day on atheroma volume in patients with coronary artery disease, and showed that the atheroma progressed by 2.7% in the pravastatin group, and remained unchanged in the atorvastatin group. At 18 months follow-up, the CRP levels were reduced from a baseline level of 2.8 mg/l to 1.8 mg/l by atorvastatin, whereas pravastatin had little effect, and there was a good correlation between both the ultrasonographic progression of disease and the reduction in CRP levels. The Pravastatin or Atorvastatin Evaluation and Infection Therapy--Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial compared the long-term effects of the standard lowering of LDL-cholesterol with pravastatin, with the intense lowering of LDL-cholesterol with atorvastatin in patients with an acute coronary syndrome. The primary end point was the first of death, myocardial infarction, unstable angina requiring hospitalisation, revascularisation or stroke, and, at the end of 2 years, was greater in the pravastatin than the atorvastatin group (26.3 versus 22.4%, respectively). Patients with CRP levels of 2 mg/l had lower rates of recurrent myocardial infarction or death from coronary causes than patients with higher levels. Further analysis should be undertaken to assess cardiovascular risk at different levels of CRP, including assessing cardiovascular risk at different levels in men and women. Definitive results about the importance of lowering CRP levels are not likely to be obtained until the results of the Justification for Use of Statins in Primary Prevention, an Intervention Trial in Evaluating Rosuvastatin (JUPITER) study are published.
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PMID:Relating statin therapy to C-reactive protein levels. 1608 47

Recently, two large randomised clinical trials compared the effects of standard and intensive lipid-lowering treatment (Pravastatin 40 mg vs. Atorvastatin 40 mg b.i.d.) on patient prognosis after acute coronary syndromes--the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT), and on the atherosclerosis regression--the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL). Undoubtedly, the event-rate reduction and the atherosclerosis regression associated to intensive hypocholesterolemic treatment in these studies are impressive, however we would like to highlight some methodological concerns raised by both trials, more clinically oriented than planned to give rigorous answers to the scientist. The main problems of both studies are that they compare the effects of statins with different pleiotropic and pharmacokinetic properties and that the metabolic disorders that affect the studied patients have not been clearly described. Moreover, it is unclear if the cardiovascular disease history length was similar in the two treatment groups as well as the length and dosage of statin treatment of the about 25% of patients taking statins before the enrollment. Waiting for studies comparing the effects of low and high dosages of the same statin or the high dosage of two similarly potent and rapid lipid-lowering effect (as for instance atorvastatin and rosuvastatin), prudence has to be applied in the interpretation (and even more in the application) of these large and expensive study results, that have yet only confirmed the relevance of a more intensive lipid-lowering treatment in all patients affected by atherosclerosis-based coronary syndromes.
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PMID:REVERSAL and PROVE-IT: are clinically oriented trials really better than "pure" scientific studies? 1609 83

Statins reduce both atherogenic lipoproteins and high-sensitivity C-reactive protein (hsCRP). The optimal strategy for administration of lipid-lowering agents has evolved considerably during the past 2 years. Several studies have compared the effects of intensive versus moderate lipid lowering in secondary prevention of coronary events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was a double-blind, randomized trial comparing the effect that 2 different statins, administered for 18 months, had on atherosclerotic burden measured by intravascular ultrasound (IVUS). At 34 centers in the United States, 654 patients were randomized to moderate lipid lowering using pravastatin 40 mg or intensive treatment with atorvastatin 80 mg. IVUS was performed during baseline catheterization and repeated after 18 months of treatment. Efficacy parameters included changes in atheroma burden determined by IVUS, lipoprotein levels, and CRP levels. Baseline low-density lipoprotein (LDL) cholesterol (mean, 3.9 mmol/L [150.2 mg/dL]) levels were reduced to 2.8 mmol/L (110 mg/dL) in the pravastatin 40-mg group compared with 2.0 mmol/L (79 mg/dL) in the atorvastatin 80-mg arm (p <0.0001). CRP decreased 5.2% with pravastatin and 36.4% with atorvastatin (p <0.0001). Changes in atheroma burden showed a significantly lower progression rate in the intensive arm for all 3 prespecified IVUS efficacy measures. For all IVUS end points, progression occurred in the moderate-treatment cohort. However, plaque volume was unchanged in the intensive arm, indicating absence of progression. Post hoc analyses demonstrated that greater reductions in both lipid levels and hsCRP were associated with slower disease progression. The slowest progression occurred in patients with above-median reductions in both LDL cholesterol and CRP. For patients with coronary artery disease, intensive treatment with atorvastatin 80 mg reduced progression of coronary atherosclerosis compared with a more moderate regimen consisting of pravastatin 40 mg. Compared with baseline, intensively treated patients had no change in atheroma burden, whereas moderately treated patients showed progression. These differences are related to the greater reduction in atherogenic lipoproteins and CRP in intensively treated patients.
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PMID:Effect of intensive lipid lowering on progression of coronary atherosclerosis: evidence for an early benefit from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial. 1612 25

Statins have become a cornerstone of treatment for dyslipidaemia primarily due to their marked lowering of low-density lipoprotein cholesterol (LDL-C). Studies show that statin treatment typically reduces relative risk of cardiovascular disease by 24-37%, regardless of age, sex, prior history of coronary heart disease (CHD), or other co-morbid conditions. There is also a growing body of evidence that statins can be effective in people whose LDL-C is not considered elevated under current guidelines. In both the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Collaborative Atorvastatin Diabetes Study (CARDS), participants randomised to atorvastatin (10 mg/day) experienced at least a one-third reduction in major cardiovascular events, even though at baseline, their LDL-C was within the normal range. Other studies have also provided evidence that more intensive lipid-lowering regimens could provide additional clinical benefits. In the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, the first active-control clinical trial of CHD progression, an intensive lipid-lowering regimen using atorvastatin (80 mg/day) decreased atherogenic lipoproteins and atheroma volume in patients with established CHD, compared with a moderate regimen using pravastatin (40 mg/day). Furthermore, relative to baseline, there was no measurable atheroma progression in the atorvastatin group. While statin therapy does offer significant clinical benefit, 60-70% of major cardiovascular events are still not prevented, which underscores the need for alternative interventions. Targeting inflammatory mediators of atherosclerosis such as C-reactive protein (CRP), as well as combination therapy to simultaneously raise high-density lipoprotein cholesterol (HDL-C) and lower LDL-C, are among the promising new strategies for primary and secondary prevention of atherosclerotic disease. This article will summarise data concerning use of statins in patients without markedly elevated LDL-C. The issue of the ideal LDL-C target will also be considered before addressing future treatment options for dyslipidaemia.
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PMID:Statins and LDL-cholesterol lowering: an overview. 1613 36

Intravascular ultrasonography is a catheter-based technique used to provide 3-dimensional views of the vessel lumen as well as the size and distribution of atherosclerotic plaques. This imaging technique was used in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study, an 18-month, randomized, controlled, multicenter trial comparing the effects of intensive versus moderate lipid-lowering therapy on plaque progression in patients requiring coronary angiography. A total of 253 patients were randomized to atorvastatin 80 mg/day (intensive lipid lowering) and 249 patients were randomized to pravastatin 40 mg/day (moderate lipid lowering). Low-density lipoprotein (LDL) cholesterol levels decreased from a baseline mean of 150 mg/dL (3.9 mmol/L) in both groups to 79 mg/dL (2.0 mmol/L) in the atorvastatin group and 110 mg/dL (2.9 mmol/L) in the pravastatin group. High-sensitivity C-reactive protein (hs-CRP) levels decreased by 36.4% in the atorvastatin group versus 5.2% in the pravastatin group (P <0.001). For the primary end point of percent change in total atheroma volume, a significantly lower rate of progression from baseline was observed with atorvastatin (-0.4%) than with pravastatin (2.7%) (P = 0.02). Linear regression analysis showed an inverse relation between lipid reduction and plaque progression for both groups; however, at any given level of LDL cholesterol, the progression rate was lower with atorvastatin compared with pravastatin. Both regimens were well tolerated. The results show that intensive lipid lowering with atorvastatin 80 mg/day for 18 months halted the progression of coronary atherosclerosis, whereas more moderate lipid lowering with pravastatin 40 mg/day was associated with progression. The differences in the progression rate are likely to be a result of greater reduction in atherogenic lipoproteins and hs-CRP with intensive therapy.
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PMID:Halting the progression of atherosclerosis with intensive lipid lowering: results from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial. 1635 4

Relative changes in lumen size during progression and regression of coronary atherosclerosis remain largely unknown. We assessed these changes using serial intravascular ultrasound (IVUS). From the baseline IVUS interrogations of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, 210 focal coronary lesions with <50% angiographic stenosis were identified. Lesions were matched to the follow-up IVUS, performed after 18 months of treatment with atorvastatin 80 mg/day or pravastatin 40 mg/day. Changes in external elastic membrane (EEM) and lumen areas of lesions demonstrating progression and regression (i.e. increased and decreased atheroma area) were examined. In progressors (n=128), there was 1.34 mm(2) increase in EEM area for every 1mm(2) increase in atheroma area (r=0.72, p<0.0001). This resulted in 0.34 mm(2) increase in lumen area for every 1mm(2) increase in atheroma area (r=0.25, p=0.004). In contrast, there was no significant change in lumen area with regression of disease (n=82, r=-0.06, p=0.59). Progression of coronary atherosclerosis can be associated with a paradoxical increase in lumen cross-sectional area, whereas regression is not associated with any change in lumen area. Measurement of changes in lumen size may not be an accurate method to study progression and regression of atherosclerotic lesions with <50% stenosis.
Atherosclerosis 2006 Nov
PMID:Paradoxical increase in lumen size during progression of coronary atherosclerosis: observations from the REVERSAL trial. 1642 43

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 is supported by experimental evidence. However, the relevance of the antioxidant hypothesis for the treatment of patients with atherosclerosis has not been definitively proven. Results of randomized trials with 'antioxidant' vitamins have been disappointing, and there are potentially important problems associated with their use, including their potential pro-oxidant effects. Probucol has reduced postpercutaneous 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. Two trials test the antioxidant/anti-inflammatory hypothesis with AGI-1067; CART-2 assesses its value for the reduction of both atherosclerosis progression and post-PCI restenosis, and Aggressive Reduction of Inflammation Stops Events (ARISE), which is evaluating its effects on hard cardiovascular outcomes.
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PMID:Antioxidants: the good, the bad and the ugly. 1649 14

Patients with type 2 diabetes mellitus are at high risk for cardiovascular events and heart failure. The major serious complication of this disorder is large vessel atherosclerosis leading to myocardial infarction and stroke. Aggressive target setting for modifiable cardiovascular risk factors such as dyslipidemia, hypertension, and a procoagulant state, and judicious choice of efficacious therapies have been shown to produce significant reductions in cardiovascular events. The effectiveness of percutaneous coronary intervention (PCI) in diabetes is discussed, and the factors that may influence outcomes are explored. A major unresolved question is the potential role of tight glucose control for reducing macrovascular complications in patients with diabetes. With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest causes of mortality in diabetic patients. This article reviews the current and emerging therapeutic strategies for these purposes from the cardiologists' point of view.
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PMID:[Type 2 diabetes mellitus and cardiovascular diseases: evaluation, treatment and prevention strategies]. 1650 21

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