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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased plasma levels of fibrinogen and C-reactive protein (CRP), as well as leukocytosis, are now established as risk factors for the thromboembolic complications of vascular disease. Chronic inflammation or infection associated with an acute-phase response--notably, periodontal disease and smoking-induced lung damage--are likewise known to increase cardiovascular risk. A common etiologic factor in these conditions may be interleukin-6 (IL-6), acting on hepatocytes to induce acute-phase reactants that increase blood viscosity and promote thrombus formation. Recent evidence that hypertrophied adipocytes release IL-6, and that hyperglycemia evokes IL-6 production by endothelium, may explain why plasma fibrinogen is increased in visceral obesity and poorly controlled diabetes. IL-6 is released by a range of tissues in response to stimulation by the monocyte-derived cytokines interleukin-1 and tumor necrosis factor; by suppressing production of these cytokines, fish oil, alpha-linolenic acid, and pentoxifylline can reduce IL-6 synthesis. Moderate ethanol consumption, as well as sex-hormone replacement, also appear to inhibit IL-6 production or activity. These practical protective measures may be of particular value to patients with pre-existing atheroma and elevated plasma levels of acute-phase reactants. Since IL-6 plays a crucial physiological role in osteoclast generation and activation, these measures may also aid preservation of bone density.
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PMID:Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline. 1041 55

C-reactive protein (CRP) is a member of the pentraxin family of proteins, which are characterised by a cyclic pentameric structure and radial symmetry. The five identical 24-kDa protomers consist of 206 amino acids, and are noncovalently linked. CRP binds to a range of substances such as phosphocholine, fibronectin, chromatin, histones, and ribonucleoprotein in a calcium-dependent manner. It is a ligand for specific receptors on phagocytic leukocytes, mediates activation reactions on monocytes and macrophages, and activates complement. Plasma CRP is the classical acute-phase protein, increasing 1,000-fold in response to infection, ischemia, trauma, burns, and inflammatory conditions. A growing number of studies suggest that CRP is an independent risk factor for atherosclerotic vascular disease. Plasma CRP concentrations in the highest quartile are associated, depending on the subject group, with 1.5- to 7-fold increases in relative risk. In the high-risk endstage renal failure population, a raised CRP is associated with up to 5.5-fold increased relative risk of CVD and 4.6-fold increased relative risk of death. This review examines the relationships between CRP, cardiovascular disease, and mortality, with special reference to renal disease.
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PMID:Review: Biology and relevance of C-reactive protein in cardiovascular and renal disease. 1080 56

Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.
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PMID:Reversing heart disease in the new millennium--the Fleming unified theory. 1095 14

Atherosclerosis remains the leading cause of morbidity and mortality in Western countries. Recent evidence has demonstrated that atherosclerosis is not simply a disease of lipid deposition. Inflammation plays a major role in the initiation, progression, and destabilization of atheromas. High-sensitivity C-reactive protein (hs-CRP) is a circulating acute-phase reactant that reflects active systemic inflammation. Large prospective trials have shown hs-CRP to be a strong predictor of future cardiovascular events. Increased hs-CRP concentration is in fact associated with higher cardiovascular events in individuals with and without clinical evidence of atherosclerotic disease. The relative risk associated with hs-CRP is independent of other cardiovascular disease risk factors. Assays for hs-CRP measurement are currently available but must be standardized because patients' results will be interpreted by using population-based cutpoints. A risk-stratifying algorithm incorporating hs-CRP and total cholesterol to high-density lipoprotein cholesterol ratio has been proposed. Further research into the mechanisms and pharmacological treatment of vascular disease will provide novel management strategies in the very near future.
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PMID:High-sensitivity C-reactive protein and atherosclerosis: from theory to therapy. 1116 6

In uremic patients, the morbidity and mortality of cardiovascular disease are substantially higher than in the general population. This has led to the formulation of an 'accelerated atherogenesis' hypothesis in uremic patients and has been commonly linked with the metabolic alterations associated with uremia. Advancement in the understanding of the pathogenesis of atherosclerotic vascular disease now suggests a central contribution of inflammation to atherogenesis, with involvement of a number of key mediators and markers of the inflammatory process. Recent epidemiological data have documented associations between C-reactive protein (CRP), the prototypical acute phase response protein, and cardiovascular disease in general population. Given the lipoprotein binding and complement activation functions of CRP and its localization in atherosclerotic vessels, there is a strong likelihood that CRP may be involved in the atherosclerotic process. The uremic state is associated with an altered immune response, which is associated with elevated proinflammatory cytokine levels. CRP concentrations are increased in a significant proportion of end-stage renal disease patients and have been associated with certain clinical outcome measures, including all-cause and cardiovascular mortality. This review outlines the evidence linking CRP with atherosclerosis and proposes that elevated CRP concentrations may be involved in the initiation and progression of accelerated atherosclerosis in uremia.
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PMID:End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link? 1116 22

In the past year, evidence from epidemiological studies in patients with renal disease has confirmed associations between both elevated plasma total homocysteine concentrations and the inflammatory marker C-reactive protein with an increased risk of arteriosclerotic vascular disease. However, it remains to be determined whether lowering total homocysteine or reducing inflammation will prevent 'hard' clinical outcome events such as stroke, myocardial infarction, and vascular death. Randomized trials of homocysteine lowering are currently ongoing and should further clarify the nature of the observed association between elevated total homocysteine and cardiovascular risk in patients with or without renal disease, and whether it is causal and modifiable. There are currently no known therapeutic interventions that specifically lower C-reactive protein levels in individuals or the prevalence of elevated C-reactive protein in the population but randomized trials of anti-inflammatory therapy (e.g. using selective cyclo-oxygenase-2 inhibitors) aimed at preventing cardiovascular disease are currently being planned.
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PMID:Associations of homocysteine, C-reactive protein and cardiovascular disease in patients with renal disease. 1134 1

C-reactive protein (CRP) is a protein whose concentration in serum is increased in response to inflammatory stimuli. Increased levels serve to identify organic disease, monitor disease activity and assist differential diagnosis. High values are observed early in bacterial infections, active rheumatoid disease, Crohn's disease, acute myocardial infarction and after major trauma. In patients with ischaemic chest pain, a raised CRP value on hospital admission is associated with an adverse prognosis. In apparently healthy individuals, a raised CRP value indicates an increased risk of developing atherosclerotic vascular disease, but also increased benefit from aspirin prophylaxis and treatment of hyperlipidaemia.
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PMID:C-reactive protein. 1140 13

Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor alpha) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition-decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
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PMID:The microinflammatory state in uremia: causes and potential consequences. 1142 86

Patients with insulin-dependent diabetes mellitus (IDDM) are well known to be at high risk of vascular disease, and dysfunction of vascular endothelium is considered as an early step in the development of diabetic complications. Because of the involvement of autoimmunity in the pathogenesis of IDDM, our aim was to assess, in 45 IDDM patients without clinically evident vascular complications, whether early signs of endothelial cell dysfunction were correlated to alterations of the immune system. IDDM patients were characterized by significantly increased serum levels of C-reactive protein, of polymorphonuclear cells-derived elastase, of endothelin-1 (ET-1) and of thrombomodulin, while plasma concentrations of fibronectin (FNT) were significantly decreased, with a statistically significant inverse correlation between ET-1 and FNT values. The presence of circulating immune complexes (CIC) was investigated in 36 out of our 45 IDDM patients, and values above the cut-off were found in 17 (47.2%) of them. One-third of all patients showed values above the cut-off for IgG-aCL. In IDDM patients, at variance from the control group, the levels of ET-1 were directly correlated to those of von Willebrand factor, of anticardiolipin beta(2)-GPI and of CIC, with an inverse correlation with plasma FNT. An association between antiphospholipid antibodies and endothelial dysfunction and/or activation is therefore suggested, pointing to a synergism, in the early phases of IDDM vascular disease, between generation of autoantibodies and endothelial activation.
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PMID:Autoantibodies and endothelial dysfunction in well-controlled, uncomplicated insulin-dependent diabetes mellitus patients. 1150 Jan 97

As renal function declines, the prevalence of both malnutrition and cardiovascular disease increase. Both malnutrition and vascular disease correlate with the levels of markers of inflammation both in patients treated with dialysis and in those not yet on dialysis. While it is possible that the markers of inflammation (increased levels of C-reactive protein (CRP) or interleukin-6 (IL-6)) are a result of inflammation arising from the atherosclerotic process, changes in endothelial cell gene expression, in plasma protein composition and in lipoprotein structure that arise from inflammation are likely to be atherogenic. The causes of inflammation are likely to be multifactorial. CRP levels are associated with cardiovascular risk in the general population and decrease following treatment with HMG-CoA reductase inhibitors. It is speculated that use of these agents or directly suppressing inflammation may have use in treating the inflammatory-malnutrition syndrome in dialysis patients.
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PMID:Role of inflammation and its treatment in ESRD patients. 1180 62


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