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

The association between dietary and lifestyle factors and intermittent claudication was investigated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort comprised 26,872 male smokers aged 50-69 years who were free of claudication at study entry. At baseline (1985-1988), subjects completed a diet history questionnaire. During a median follow-up period of 4 years (ending in spring 1993), 2,578 men reported symptoms of claudication on the Rose questionnaire, which was administered annually. Smoking status was assessed every 4 months. Smoking, systolic blood pressure, serum total cholesterol, and diabetes mellitus were positively associated with risk for claudication, whereas serum high density lipoprotein cholesterol, education, and leisure time exercise were inversely associated with risk. Dietary carbohydrates, fiber, and n-6 polyunsaturated fatty acids were inversely associated with risk for claudication, as were some dietary and serum antioxidants: dietary vitamin C (highest quartile vs. lowest: relative risk (RR) = 0.86; 95% confidence interval (CI): 0.77, 0.97), dietary gamma-tocopherol (RR = 0.89; 95% CI: 0.79, 1.00), dietary carotenoids (RR = 0.82; 95% CI: 0.73, 0.92), serum alpha-tocopherol (RR = 0.88; 95% CI: 0.77, 1.00), and serum beta-carotene (RR = 0.77; 95% CI: 0.68, 0.86). Smoking cessation reduced subsequent risk for claudication (RR = 0.86; 95% CI: 0.75, 0.99). The authors conclude that classical risk factors for atherosclerosis are associated with claudication. High intakes of antioxidant vitamins may be protective. Further research is needed before antioxidants can be recommended for the prevention of intermittent claudication.
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PMID:Prospective study of diet, lifestyle, and intermittent claudication in male smokers. 1079 62

To explore the relationship between disorders of endogenous fibrinolysis and thrombosis in patients with lower extremity ischemia, we measured the activity of tissue plasminogen activator (tPAac) and plasminogen activator inhibitor (PAlac) and the antigens of tissue plasminogen activator (tPAa) and inhibitor (PAla) in plasma from 420 patients treated for lower extremity ischemia. Values and ratios observed were compared with those in healthy volunteers. Additionally, values and ratios in the patients were examined with respect to the severity of ischemia and site of atherosclerotic occlusion or stenosis (pelvic compared with femoropopliteal or crural). Patients with lower extremity ischemia had higher plasma concentrations of PAla (p<0.01) and PAlac (p<0.0001) than healthy volunteers. In patients with rest pain or gangrene, the ratio of tPAac to PAlac was higher than in patients with claudication (p<0.05). The elevation of tPAac in patients with the more severe form of lower extremity ischemia is probably the feedback protective reaction on prothrombotic mechanisms of the organism suffered from severe atherosclerosis. Results did not vary according to the site of occlusion or stenosis. Our study found defects in endogenous fibrinolysis in patients with lower extremity ischemia. A defect in fibrinolysis may contribute to the development of thrombosis in native arteries and bypasses.
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PMID:Endogenous fibrinolysis in patients with lower extremity ischemia. 1094 87

Intermittent claudication is a symptom complex associated with atherosclerosis of the aorta and lower extremities. It is a clinical marker of systemic atherosclerosis, and therefore, management cannot be considered isolated from treatment of underlying risk factors of atherosclerosis. The focus of the management is twofold. The first is to reduce morbidity and mortality from cardiovascular events, including myocardial infarction and stroke. The second focus is to improve the functional status of patients who have impairment of daily activities secondary to symptoms of claudication through pharmacologic and rehabilitative means, that is, exercise. Exercise is the cornerstone of therapy. A conservative approach is favored in patients who have mild and moderate symptoms of claudication. Intervention with percutaneous techniques or surgery is generally reserved for patients who have severe impairment of lifestyle or threatened tissue.
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PMID:Diagnosis and medical management of patients with intermittent claudication. 1110 62

Atherosclerosis (and its evolution towards thrombotic accidents) is now considered to be an inflammatory disease in which the interaction among endothelium, leukocytes and platelets plays a determining role. However, large scale epidemiological studies only indirectly reveal the leukocyte activation through somewhat simplistic markers, such as elastase or leukocyte counts. Interestingly, these markers seem to be independent predictors of ischemia distal to the atheromatous lesion. This leukocyte activation is usually associated with more classical hemorheological disturbances affecting blood viscosity and fibrinogen which, on multivariate analysis, also appear to be determinants of atheromatous lesions and their ischemic and thrombotic consequences, statistically independent of the "classical risk factors". Leukocyte activation probably plays an important role in these hemorheological disturbances, because it is associated with the production of leukocyte secretory products (proteolytic enzymes, free radicals, cytokines) which can alter the red cells and make them more aggregable and more rigid, and can increase the production of fibrinogen. These interactions remain incompletely understood, as illustrated by the still unclear role of NO which, depending on the experimental conditions, can have antiatherogenic or proatherogenic effects. The production by the leukocyte of substances leading to hyperviscosity is amplified by hypoxia, while the improvement in claudication distance resulting from walking exercise is associated with a joint fall of the "classical" factors of viscosity and of leukocyte activation markers. All this suggests that leukocyte activation and hyperviscosity are closely interdependent phenomena in the course of atheromatous disease and that, despite the complexity of these interactions, relatively simple and reasonably priced biological markers of this process will become available to the clinician.
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PMID:[Hemorheological aspects of leuko-platelet activation in atheromatous diseases: clinical applications]. 1114 97

Intermittent claudication is the most common symptom in patients with peripheral arterial disease (PAD). As such, it is mandatory for clinicians to treat both the PAD-specific symptoms (to decrease functional impairment and thereby improve quality- of-life, as well as to decrease rates of amputation) and the underlying systemic atherosclerosis (and thereby reduce cardiovascular ischemic events, especially myocardial infarction and stroke). Most patients with claudication can successfully decrease their exertional limb symptoms via a combination of exercise (preferably supervised) and pharmacotherapeutic interventions (eg, cilostazol). Endovascular revascularization currently serves as an effective therapy for patients with high-grade stenoses of the proximal limb arterial segments, (eg, the distal aorta, common iliac artery, or external iliac artery, and occasionally the proximal common femoral artery). Surgical revascularization usually is reserved for patients who present with severe aortoiliac disease in whom long-term patency is likely to be achieved (eg, aortobifemoral or femoral-femoral bypass) and who have a low cardiovascular perioperative ischemic risk. Patients who undergo successful revascularization also are likely to benefit from exercise rehabilitation programs. All patients with PAD, of any severity, must successfully normalize atherosclerosis risk factors and use antiplatelet therapies. Such interventions include complete smoking cessation, glycemic control, normalization of blood pressure (less than 130/90 mm Hg), and lowering of low-density lipoprotein (LDL) cholesterol to less than 100 mg/dL. Antiplatelet agents (eg, clopidogrel, aspirin) should be prescribed to decrease rates of cardiovascular ischemic events in all patients with PAD, unless otherwise contraindicated.
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PMID:Intermittent Claudication. 1134 62

Transcatheter endovascular procedures are increasingly used to treat symptomatic peripheral atherosclerosis. This two-part review identifies the existing evidence supportive of the application of transcatheter treatments for peripheral atherosclerotic lesions. The first part addresses the treatment of obstructive lesions that cause limb claudication and critical ischemia, renovascular hypertension and azotemia, and mesenteric ischemia. Studies were identified via a search of MEDLINE (January 1993 through April 1999) and reference lists of identified articles. When multicenter prospective randomized trials or other high-quality studies were unavailable, a preference was given to studies with at least 50 patients per treated group and a minimum mean follow-up duration of 6 months. Data presented in tables are proportionally weighted averages from included studies. For each application, the authors assessed the quality of evidence (QOE; efficacy, safety, and, where available, cost-effectiveness) and made recommendations with appropriate caveats. There is higher QOE supporting the more established treatments such as lower limb percutaneous transluminal angioplasty (PTA) with stent placement and thrombolysis. Treatments such as renal artery PTA and stent placement and mesenteric and brachiocephalic PTA are in wide use, but high QOE supporting general application is lacking. Blanket recommendations based on established efficacy and cost-effectiveness cannot be made. However, the use of transcatheter therapies can be supported in specific circumstances based on an expected reduction in procedure-related morbidity and/or mortality rates. It is hoped that the identification of deficiencies in the literature will inform and inspire critically needed research in this area.
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PMID:Transcatheter interventions for the treatment of peripheral atherosclerotic lesions: part I. 1138 19

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.
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PMID:Medical management of peripheral arterial disease. 1140 4

Intermittent claudication (IC), the symptom of exercise-induced muscle ischemia of peripheral arterial disease (PAD), afflicts and limits the activities of a significant number of patients. Incidence and prevalence of IC depends on the population studied and the diagnostic instruments used. In large studies, prevalence has ranged from 3% to 10%, with a sharp increase in those aged > or =70 years. Over the next 20 years, the total number of patients affected is expected to increase significantly due to anticipated demographic changes. Analysis of the natural history of IC demonstrates that the risk of cardiovascular morbidity and mortality far exceeds that of severe limb ischemia or limb loss. In fact, only 2% to 4% of all patients with IC will require a major amputation in their lifetime. However, life expectancy is approximately 10 years less than that of an age-matched cohort. By now, PAD is well recognized as a marker of systemic atherosclerosis. The cornerstone of patient evaluation is a history and physical examination, including a detailed atherosclerotic risk-factor assessment. In the differential diagnosis of IC, clinicians should consider etiologies such as arthritis, spinal stenosis, radiculopathy, venous claudication, or inflammatory processes. In >80% of all patients, it is possible to locate the responsible arterial segment by combining the location and severity of pain with a pulse examination. Noninvasive diagnostic studies help determine the level of disease, may unmask a hemodynamically significant stenosis, and are useful in follow-up. Arteriography is reserved for patients in whom the decision for revascularization has been made. Knowing the anatomic detail of a lesion allows the clinician to determine whether and what type of intervention is feasible. Standard therapy for all patients should be directed at both peripheral and systemic atherosclerosis, beginning with risk-factor modification in the form of smoking cessation, optimal diabetes control, and lipid normalization. The benefits of supervised exercise rehabilitation include significantly increased walking distance and enhanced quality of life. Platelet inhibition has been shown to reduce the risk of ischemic stroke, myocardial infarction, and vascular death and should be prescribed for all but those in whom it is medically contraindicated. Symptom-specific pharmacotherapy with a broad range of medications has yielded disappointing results in the past. However, recent studies have demonstrated that patients receiving the novel agent cilostazol experienced increases in walking distance and improvements in quality of life.
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PMID:Intermittent claudication: magnitude of the problem, patient evaluation, and therapeutic strategies. 1143 94

The Minnesota Regional Peripheral Arterial Disease Screening Program was designed to define the efficacy of community PAD detection efforts, to assess the disease-specific and health-related morbidity, to assess PAD awareness rates, and to determine the magnitude of atherosclerosis disease risk factors and the intensity of their management. The target population was recruited via mass media efforts directed at individuals over 50 years of age and those with leg pain with ambulation. Screening sessions included assessments of the ankle-brachial index, blood pressure, fasting lipid profile, and use of validated tools to detect symptomatic claudication (by the Modified WHO-Edinburgh Claudication Questionnaire), walking impairment (Walking Impairment Questionnaire - WIQ), quality of life (MOS SF-36), PAD awareness, and the intensity of PAD medical therapeutic interventions. PAD was defined as any ankle-brachial index < or =0.85 or a history of lower extremity revascularization. The program evaluated 347 individuals and identified 92 subjects with PAD and 255 subjects without PAD, yielding a detection rate of 26.5%. Individuals with PAD were older, tended to have higher blood pressures, and had a significant walking impairment and an impaired health-related quality of life compared with the non-PAD subjects. Current rates of tobacco use were low. Lipid-lowering, estrogen replacement, anti-platelet, and antihypertensive medications and exercise therapies were underutilized in the PAD cohort. Peripheral arterial disease awareness was low in these community-identified patients. This Program demonstrated that individuals with PAD can be efficiently identified within the community, but that current standards of medical care are low. These data can assist in the future development of PAD awareness, education, and treatment programs.
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PMID:The Minnesota Regional Peripheral Arterial Disease Screening Program: toward a definition of community standards of care. 1153 Sep 70

Considering the morphological findings in egyptian mummies at the beginning of the 20th century, atherosclerotic lesions were also apparent in pharaoh mummies more than 3500 years ago. Hippokrates (469-377 b.c.) described the sudden (cardiac) death, whereas Erasistratos had documented the typical claudication intermittens symptoms of peripheral arterial disease approximately 300 b.c. Later on in 1575, Fallopius observed severe pathological findings in arteries which he has characterized as a 'degeneration to bones', suggesting the presence of calcified atherosclerotic lesions. The relation between coronary lesions and the symptoms of angina pectoris was postulated in 1799 by Parry, however, only more than 80 years later angina pectoris was interpreted as a result of myocardial ischemia by Potain. During that time, the term 'arteriosclerosis' was firstly created by Lobstein in his 'Lehrbuch der pathologischen Anatomie', published in 1835. With the beginning of the last century, the pathophysiological aspects of plaque development were investigated in more detail by a number of researchers. In this context, people such as Saltykow, Chalatow and Anitschkow are important to notice. In 1914, Anitschkow firstly described the role of cholesterol accumulation in the vessel wall for the development of atherosclerosis. He used a cholesterol-fed rabbit model, which is the most important model of experimental atherosclerosis up to now. He also firstly described the 'Cholesterinesterphagozyten', which today commonly are known as foam cells, derived from macrophages. Using the cholesterol-fed rabbit model as well, already in 1942, Ludden et al. could demonstrate the atheroprotective effect of estrogen experimentally, a finding, which got later confirmed in the primate model and epidemiological studies. In the last three decades our knowledge has expanded by a large number of findings, based on morphological, immunohistological and molecular methods. In this context, one major contribution was the discovery of the LDL-receptor and its importance for the development of atherosclerosis by Brown and Goldstein, and the setting up of the 'response to injury hypothesis' by Ross and Glomset. At the present, we understand atherosclerosis as a complex (and at least in part as a physiological) phenomenon, beginning in the early childhood. The pathological aspect, making it to a disease, is depending on individual growth dynamics and plaque localization. The following key processes during the development of atherosclerosis are identified: 1) Endothelial injury, 2) intimal cholesterol accumulation and monocyte invasion with subsequent foam cell formation, 3) migration and proliferation of smooth muscle cells with expression of extracellular matrix 4) local thrombus formation with secondary organization 5) calcification and/or plaque rupture 6) final occlusion due to plaque rupture/thrombus formation. The classical concept of cardiovascular risk factors does only partially explain the origin of atherosclerosis. For the future, further mechanism(s) need to be identified and studied (genomic pathways, hormonal aspects, infective components, etc.) probably opening an effective therapeutical strategy to prevent and treat atherosclerotic diseases.
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PMID:The discovery of the pathophysiological aspects of atherosclerosis--a review. 1168 58


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