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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrovascular impairment of peripheral arteries in diabetes mellitus corresponds with such an impairment in atherosclerosis. Furthermore, peripheral angiopathy, microangiopathy, and polyneuropathy resulting from microangiopathy develop in diabetes. Impairment of microcirculation worsens peripheral blood flow. Infection and insufficient trophism worsen state. A wide range of factors participate in development of vascular disease in diabetes with adverse influence both on veins and reactions coming under rheology, haemocoagulation, and immune reactions. In type II diabetes an average interval of arterial impairment is 9-10 years, in type I diabetes approximately 17-22 years. A relative risk of non-traumatic amputation of a lower limb in diabetics is several times higher than in non-diabetics. A prevention of lower limbs impairment in diabetics is the most efficient method of reducing risk of amputation. An intervention therapy, endovascular intervention or angiosurgery are indicated in patients with clinical problems. A state of distal bed is an important factor for success of interventions. As a pivotal drug treatment in intervention and traditional methods is considered an effective antiaggregation treatment. A diabetic peripheral arterial disease is a complex disease requiring a wide view and considering various and changing pathophysiological mechanisms.
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PMID:[Diabetic peripheral arterial disease]. 1504 Jan 54

By the turn of the last century, flying in the face of over a hundred years of research and clinical observation to the contrary, medicine abandoned the link between infection and atherogenesis; not because it was ever proven wrong, but because it did not fit in with the trends of a medical establishment convinced that chronic disease such as heart disease must be multifactorial, degenerative and non-infectious. Yet it was the very inability of 'established' risk factors such as hypercholesterolemia, hypertension and smoking to completely explain the incidence and trends in cardiovascular disease that resulted in historically repeated calls to search out an infectious cause, a search that began more than a century ago. Today, half of US heart attack victims have acceptable cholesterol levels and 25% or more have none of the "risk factors" associated with heart disease, including smoking, high blood pressure or obesity, most of which are not inconsistent with being caused by infection. Even the case of the traditionalist's latest 2003 JAMA assault to 'debunk' what they call the "50% risk factor myth" falls woefully short under scrutiny. In one group 30% died of heart disease with a cholesterol of at least 240 mg/dl, a condition which also existed in 21% who did not die during the same period. And the overlap was obvious throughout the so-called risk categories. Under such scrutiny, lead author Greenland conceded that if obesity, inactivity and elevated cholesteriol in the elderly are included, just about everyone has a risk factor and he likened the dilemma of people who do or do not wind up with heart disease akin to the susceptibility of people who are exposed to tuberculosis but do not get the disease. In Infections and Atherosclerosis: New Clues from an old Hypothesis? Nieto stressed the need to extend the possible role of infectious agents beyond the three infections which have in recent years been the focus of research: Cytomegalovirus (CMV) Chlamydia pneumoniae and Helicobactor pylori. Mycobacterial disease shares interesting connections to heart disease. Not only is tuberculosis the only microorganism to depend on cholesterol for its pathogenesis but CDC maps for cardiovascular disease bear a striking similarity to those of State and regional TB case rates. Ellis, Hektoen, Osler, McCallum, Swartz, Livingston and Alexander-Jackson all saw clinical and laboratory evidence of a causative relationship between the mycobacteria and heart disease. And Xu showed that proteins of mycobacterial origin actually led to experimental atherosclerosis in laboratory animals Furthermore present day markers suggested as indicators for heart disease susceptibility such as C-Reactive Protein (CRP), interleukin-6 and homocysteine are all similarly elevated in tuberculosis. It therefore behooves us to explore the link between heart disease and typical and atypical tuberculosis.
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PMID:Heart disease: the greatest 'risk' factor of them all. 1508 5

Statins, as compared to placebo, have proven their efficacy in reducing cardiovascular events in patients with or without cardiovascular disease and in a large range of cholesterol levels. Two new head-to-head randomised trials comparing intensive treatment with atorvastatin 80 mg/day with moderate treatment with pravastatin 40 mg/day were recently completed. The mechanistic "Reversing Atherosclerosis with Aggressive Lipid Lowering" (REVERSAL) trial randomised 502 patients with stable coronary disease. Atorvastatin 80 mg (leading to a mean LDL cholesterol of 79 mg/dl) was superior to pravastatin 40 mg (mean LDL of 110 mg/dl) in terms of limiting the progression of atheroma assessed with the use of intravascular ultrasonography after 18 months of follow up (p = 0.02). These differences may be related to the greater reduction in atherogenic lipoprotein (-46% versus -26%, p < 0.001) and C-reactive protein (-36% versus -5%, p < 0.001) in patients treated with atorvastatin as compared to pravastatin. In the clinical "Pravastatin or Atorvastatin Evaluation and Infection Therapy" (PROVE-IT) trial, 4162 patients with acute coronary syndromes were randomised to either atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months. Again, atorvastatin (mean LDL of 62 mg/dl) was superior to pravastatin (mean LDL of 95 mg/dl), resulting in a 16% percent lower risk of the primary end point, a composite of major cardiovascular events (p = 0.005). Thus, both REVERSAL and PROVE-IT support the concept "the lower, the better". However, they do not allow to disentangle the independent and interdependent effects of statins on LDL cholesterol and the process of arterial inflammation. What so ever, the results suggest that the target LDL cholesterol level may be lower than recommended in the current guidelines in high-risk patient so that a sea change in the prevention and management of atherosclerotic vascular disease may occur very soon.
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PMID:[Clinical study of the month. REVERAL and PROVE-IT: confirmation of the concept " the lower, the better" for cholesterol therapy in patients with coronary heart disease]. 1513 6

Current international guidelines recommend that the goal of treatment with lipid-lowering therapy in patients with established coronary artery disease (CAD) should be a low-density lipoprotein cholesterol level of < 100 mg/dl. The question that remains to be answered is whether more aggressive lowering of low-density lipoprotein cholesterol levels below this target offers additional benefit and whether it can be tolerated. Two recently published related studies addressed this question by comparing intensive lipid lowering with atorvastatin (Lipitor, Pfizer) 80 mg/day with a moderate lipid-lowering regimen of pravastatin (Pravachol, Bristol-Myers Squibb) 40 mg/day. The first study, the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) compared the effect of the two regimens on coronary artery atheroma burden and progression using intravascular ultrasound in patients with symptomatic CAD. The second study, the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) was a clinical outcome trial in patients recently hospitalised with acute coronary syndromes. This article reviews the implications of these two studies in the management of patients with CAD. In addition, other ongoing trials and future directions are explored.
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PMID:Intensive lipid-lowering therapy in coronary artery disease: implications of the REVERSAL and PROVE-IT trials. 1517 57

Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of MEF2 in vascular inflammation and that of p38 in the activation of MEF2, we infected cultured rat vascular smooth muscle cells (VSMCs) with an adenovirus construct expressing a dominant-negative mutant of MEF2A (MEF2ASA) or mitogen-activated protein kinase kinase 6 (MEK6AA), and examined their effects on the expression of monocyte chemoattractant protein-1 (MCP-1), which is known to play important roles in vascular inflammation. We also examined the role of MEF2 in vivo using a rat model of transluminal wire-induced injury of the femoral artery. Angiotensin II (Ang II)-induced expression of MCP-1 mRNA was significantly inhibited by infection with adenoviruses encoding MEF2ASA (AdMEF2ASA) or MEK6AA. Ang II-induced increase of MCP-1 promoter activity was also significantly suppressed by overexpression of MEF2ASA or MEK6AA. Ang II stimulated the transactivating function of MEF2A and this activation was inhibited by overexpression of MEK6AA. Infection with AdMEF2ASA suppressed MCP-1 expression in the femoral artery after the transluminal mechanical injury. AdMEF2ASA infection also inhibited macrophages infiltration and neointimal formation in the wire-injured femoral arteries. These results suggested that MEF2 activation via the p38-dependent pathway mediates vascular inflammation via stimulation of MCP-1 expression in VSMCs and macrophages infiltration.
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PMID:Myocyte enhancer factor 2 mediates vascular inflammation via the p38-dependent pathway. 1517 40

Infections, such as by Chlamydophilia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori, have been shown to be involved in atherogenesis. Herpes simplex virus I (HSV-1) could infect vascular endothelial cells, and it has been shown that, when endothelial cells were activated with oxidized LDL (oxLDL), a number of cellular events are occurred, leading to endothelial cell dysfunction. Since LOX-1 is a major receptor for oxLDL on endothelial cells and its expression was increased in atherosclerosis, we investigated whether HSV1 infection can lead to the increase expression of LOX-1 in endothelial cells. LOX-1 mRNA expression determined by RT-PCR and LOX-1 promoter activity measured by luciferase assay were increased in endothelial cells following HSV-1 infection. This suggests that one of the mechanisms by which HSV-1 is involved in atherogenesis maybe the enhanced uptake of oxLDL via the increased expression of LOX-1 in endothelial cells.
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PMID:Herpes simplex virus 1 induced LOX-1 expression in an endothelial cell line, ECV 304. 1527 8

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

The metabolic effects of obesity have made this highly prevalent disease one of the most common risk factors for diabetes, hypertension, and atherosclerosis, the leading causes of end-stage renal failure. However, obesity per se, as defined by body mass index, is less predictive of the development of these diseases than is the presence of a constellation of obesity-related abnormalities now known as the metabolic syndrome. Recognition of this syndrome, which can readily be identified in clinical settings using defined threshold values for waist circumference, BP, fasting glucose, and dyslipidemia, allows for earlier intervention in these high-risk patients. Systemic insulin resistance has been implicated as one possible factor that links visceral obesity to adverse metabolic consequences; however, the mechanism whereby adipose tissue causes alterations in insulin sensitivity remains unclear. Infection and inflammation are commonly associated with insulin resistance, and visceral obesity is associated with a chronic, low-grade inflammatory state, suggesting that inflammation may be a potential mechanism whereby obesity leads to insulin resistance. Moreover, adipose tissue is now recognized as an immune organ that secretes numerous immunomodulatory factors and seems to be a significant source of inflammatory signals known to cause insulin resistance. Therefore, inflammation within white adipose tissue may be a crucial step contributing to the emergence of many of the pathologic features that characterize the metabolic syndrome and result in diabetes and atherosclerosis. This review describes the role of proinflammatory cytokines and hormones released by adipose tissue in generating the chronic inflammatory profile associated with visceral obesity.
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PMID:The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. 1550 32

Infection with Chlamydia pneumoniae has been suggested to play a role in the development and maintenance of atherosclerosis. However, the course of C. pneumoniae infection is not clarified. Thus, both the persistence of C. pneumoniae DNA in blood and the tendency to recurrence have not been studied. We determined the prevalence of C. pneumoniae DNA in the white cells of the peripheral blood in 98 dialysis patients and in 52 healthy subjects. Blood samples were collected approximately 6 times from each subject during a period of 1 y with an interval of approximately 2 months and analysed with a polymerase chain reaction. C. pneumoniae DNA was detectable in 47 out of 150 subjects at least once during a y. Reinfection was a rare phenomenon and the presence of C. pneumoniae DNA in blood was of less than 2 months' duration in almost all patients. There was a significant association between the presence of C. pneumoniae DNA during 1 y and the presence of atherosclerosis in the legs of dialysis patients (OR=3.50, p=0.03). Additionally, a significant association was found between the presence of C. pneumoniae DNA and an abnormal electrocardiogram (ECG) (OR=3.16, p=0.01). These findings may support the hypothesis of an association between infection with C. pneumoniae and the presence or development of atherosclerosis.
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PMID:Repetitive measurements of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in healthy control subjects and dialysis patients: a prospective study. 1551 96


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