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

Oxidative stress which results from an imbalance between reactive oxygen species production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pathologies such as accelerated atherosclerosis, amyloidosis and anemia. In order to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be responsible for the imbalance between pro- and antioxidative mechanisms. The inflammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species contributing by this way to worsen the prooxidant status of uremic patients. Two factors largely contribute to the stimulation of the NADPH oxidase: hemoreactivity of the membrane and trace amounts of endotoxins. The antioxidant system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant system mainly by losses of (a) hydrophilic unbound small-molecular-weight substances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compounds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatibility of the dialysis system mainly by using a dialyzer with low hemoreactivity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achieved by oral or perdialytic supplementation. Vitamin E could be bound on dialyzer membrane. Alternatively, hemolipodialysis consists in loading HD patients with vitamin C or E via an ancillary circuit made of vitamin E-rich liposomes. The presence of liposomes could also facilitate the removal of hydrophobic prooxidative substances.
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PMID:Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance. 1085 22

The proband is a 50 year-old woman born from a consanguineous marriage. She has been suffering from angina pectoris since the age of 38 and underwent coronary bypass surgery for three-vessel disease at 48. The presence of low plasma levels of total cholesterol and high density lipoprotein (HDL) cholesterol (2.4 and 0.1 mmol/l) and apo AI (<15 mg/dl), associated with corneal lesions and a mild splenomegaly suggested the diagnosis of Tangier disease. However, none of the other features of Tangier disease, including hepatomegaly, anemia and peripheral neuropathy, were present. The analysis of the dinucleotide microsatellites located in chromosome 9q31 region demonstrated that the proband was homozygous for the alleles of D9S53, D9S1784 and D9S1832. The mother and son of the proband, both with low levels of HDL cholesterol, shared one of the proband's haplotypes, whereas neither of these haplotypes was present in the normolipidemic proband's sister. The sequence of ATP-binding cassette transporter 1 (ABC1-1) cDNA obtained by reverse transcription-PCR (RT-PCR) of total RNA isolated from cultured fibroblasts showed that the proband was homozygous for a C>T transition in exon 13, which caused a tryptophane for arginine substitution (R527W). This mutation was confirmed by direct sequencing of exon 13 amplified from genomic DNA. It can be easily screened, as the nucleotide change introduces a restriction site for the enzyme Afl III. R527W substitution occurs in a highly conserved region of the NH2 cytoplasmic domain of ABC1 protein. R527W co-segregates with the low HDL phenotype in the family and was not found in 200 chromosomes from normolipidemic individuals.
Atherosclerosis 2001 Feb 15
PMID:A point mutation in ABC1 gene in a patient with severe premature coronary heart disease and mild clinical phenotype of Tangier disease. 1125 60

Plasma homocysteine (tHcy) is an important risk factor for atherosclerosis in dialysis patients. Few data were reported on the prevalence and severity of hyperhomocysteinemia in peritoneal dialysis (PD) patients. In addition, little attention was paid to the search of factors possibly involved in the pathogenesis of hyperhomocysteinemia in these patients. A cross-sectional study was performed in 107 stable PD patients. None of them was given folate or vitamin B12 supplementation before or during the study. Plasma tHcy, serum vitamin B12, serum and erythrocyte folate were measured by immunoenzymatic methods. Genetic analysis of the methylentetrahydrofolate-reductase thermolabile mutation (tMTHFR) was performed in 61 patients. 97% of patients had tHcy levels higher than normal. tHcy was not different between men and women, patients with or without malnutrition, with or without clinically evident atherosclerotic vasculopathy, with or without anemia. tHcy levels were significantly higher in homozygotes for the tMTHFR mutation than in patients carrying the wild type form. Significant univariate correlation was found between hyperhomocysteinemia and time since the start of dialysis, serum and erythrocyte folate and vitamin B12. The best fitted model equation was log tHcy = 108.53 + 0.1606 (duration of dialysis) -1.1053 (s-F) -0.7980 (age) 0.0215 (vitamin B12). Our results agree with those reported by other authors in hemodialysis patients. Despite the large number of PD patients with normal serum vitamin B12 and folate status, the relation between tHcy and vitamin B12 or folate suggests that the supplementation of these vitamins could be useful irrespective of their serum levels, especially in younger patients or in those treated for a long period of time with peritoneal dialysis.
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PMID:Homocysteine, vitamin B12, serum and erythrocyte folate in peritoneal dialysis patients. 1133 18

Patients with chronic uremia have a substantially elevated risk of death from cardiovascular disease than do the general population. Although uremic and nonuremic groups share some of the risk factors for cardiovascular mortality, such as older age, diabetes, and inflammation, other factors appear to affect cardiovascular mortality in the opposite direction. For example, being overweight and having hyperlipidemia are established risk factors in the general population, whereas lower body mass index and lower plasma cholesterol have been shown to be risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This paradoxical phenomenon is explained by two facts: (1) that malnutrition is a strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid levels are lowered in malnutrition. However, it is not known whether atherosclerosis is promoted by malnutrition or by low cholesterol level. Because the cardiovascular mortality rate is theoretically the product of event rate and fatality rate after an event, risk factors for cardiovascular mortality could fall into two categories: those raising the event rate and those affecting the fatality rate. Some factors could work both ways. Patients with ESRD show a significant increase in both event rate and fatality rate. Dyslipidemia is an independent factor affecting atherosclerotic arterial wall changes and cardiovascular events in ESRD. Other factors affecting the cardiovascular event rate in ESRD include diabetes and an elevated homocysteine level. In contrast, factors associated with poor survival after an event include diabetes and anemia. Malnutrition could be a factor causing the fatality rate to rise, although there is no direct evidence supporting this possibility. Further studies are needed to show the differential effects of a risk factor on event rate and fatality rate. Patients with ESRD would have a better chance of living longer by better management of the two categories of risk factors.
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PMID:Paradox of risk factors for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia? 1157 13

Anaemia is a frequent complication of many diseases but the mechanisms that link reduced blood oxygen content to the long-term consequences of anaemia are incompletely understood. The maintenance of oxygen supply to the tissues during anaemia involves complex cardiovascular adaptations, including an increase in cardiac output, reduced peripheral resistance and increased oxygen extraction from haemoglobin (Hb). In addition, hypoxia-inducible factors are associated with the transcriptional activation of genes involved in adaptive mechanisms that increase oxygen delivery and provide alternative metabolic pathways. The complex pathophysiology of chronic kidney disease alters the adaptations to anaemia in uraemic patients. The increased cardiac output induced by anaemia is associated with left ventricular hypertrophy and cardiac disease in renal patients. Alterations in endothelial cell function, common in renal disease, may diminish endothelium-induced vasodilatation, increase the risk of atherosclerosis and impair angiogenesis. Many potential reasons for erythropoietin-induced hypertension in uraemic patients have been postulated, including increased blood viscosity as haematocrit rises, a reversal of hypoxic vasodilatation, increased blood volume that is not compensated by haemodialysis, ultrafiltration and impaired nitric oxide synthesis, preventing vascular relaxation in response to increased blood viscosity. In view of this impaired vascular reactivity, rapid increases in haematocrit should be avoided during epoetin treatment. As the interaction between anaemia and uraemia is very complex, it is not possible to derive the optimal Hb concentration for individual patients by using simple physiological or pathophysiological models and there is a need for good randomized controlled clinical trials to address this issue.
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PMID:Anaemia in end-stage renal disease: pathophysiological considerations. 1159 Feb 49

Chronic inflammation is a common feature of end-stage renal disease (ESRD) that is gaining increasing attention as a major cause of morbidity and mortality. It is well established that ESRD per se carries a heightened risk of inflammatory disorders and other co-morbid conditions, but it should also be pointed out that dialysis treatment per se can bring additional risk factors for inflammation, such as impure dialysate or bio-incompatible membranes. Inflammation has recently been associated with atherosclerosis and malnutrition in ESRD, and this link has led to the development of the malnutrition, inflammation, atherosclerosis (MIA) hypothesis. This describes a syndrome whereby raised levels of pro-inflammatory cytokines (such as IL-1, IL-6 and TNF-alpha) are a common link between malnutrition, inflammation and atherosclerosis. Also, anaemia appears to be an important element linking elevated cytokine levels with poor patient outcomes. Several mechanisms for cytokine-induced anaemia have been proposed, including intestinal bleeding, impaired iron metabolism and suppression of bone marrow erythropoiesis and erythropoietin production. These effects suggest that pro-inflammatory cytokines may also be an important cause of lack of response to recombinant human erythropoietin (rh-Epo) therapy. In the light of this putative role of pro-inflammatory cytokines, anti-cytokine agents may prove useful to optimize efficacy of rh-Epo in anaemic chronic renal failure patients. Other potential therapeutic strategies include minimizing exposure to causes of inflammation from various co-morbid conditions, such as persistent infections and chronic heart failure.
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PMID:The role of inflammation in the anaemia of end-stage renal disease. 1159 Feb 55

The pathogenesis of anterior ischemic optic neuropathy (AION) primarily involves interference with the posterior ciliary artery blood supply to the prelaminar optic nerve. Uremic patients often have coexisting pathology such as hypotension (decreased blood delivery), or hypertension, atherosclerosis (increased resistance to blood supply), and anemia (low blood oxygen carrying capacity), predisposing them to AION. We describe a 49-year-old patient on dialysis for many years. He had long-standing hypotension, worsened during each dialysis treatment. He awoke one morning at age 48 complaining of blurred vision in the left inferior field. Based on the clinical course, funduscopic and fluorangiographic examination and visual field defects, AION was diagnosed. Nine months after the loss of vision in the left eye, vision in the right eye became blurred and worsened over the next 24 hours. The diagnosis of AION in the right eye was made. At the last examination ten months later, the patient, still amaurotic, was given a very poor prognosis for further recovery of the visual defects. Surprisingly, very few cases of AION have been reported in chronic uremic patients on dialysis: to the best of our knowledge, only 12 including ours. Most of these cases share some features, including hypotension above all and anemia as common risk factors. Neither the type of dialysis treatment (hemo-, peritoneal dialysis) nor sex seem to have any influence on the occurrence of AION. Uremic children can be affected. What is striking in the three published pediatric cases is that they all had polycystic kidney disease. Treatment of AION in all 12 cases consisted of a combination of steroids, i.v. saline, blood transfusions and rhEpo. AION was more frequently bilateral and irreversible, ending in permanent amaurosis. In conclusion, this study aims to stress that most cases of AION occurring in chronic uremic patients on dialysis have some common features, including hypotension above all and anemia as common risk factors.
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PMID:Anterior ischemic optic neuropathy and dialysis: role of hypotension and anemia. 1173 Feb 78

Angina pectoris is a clinical syndrome of discomfort in the chest, jaw, arm, or other sites which is associated with myocardial ischaemia. The nature of angina has many individual variations, and it is easier first to consider the typical syndrome. It is hard to better the descriptions of William Heberden: There is a disorder of the breast, marked with strong and peculiar symptoms, considerable for the danger belonging to it.... Those who are afflicted with it are seized, while they are walking, and more particularly when they walk soon after eating, with a painful and most disagreeable sensation in the breast.... the moment they stand still all this uneasiness vanishes. After it has continued some months, it will not cease so instantaneous upon standing still ... (most) whom I have seen, who are at least twenty, were men, and almost all above 50 years old, and most of them with a short neck, and inclining to be fat.... But the natural tendency of this illness be to kill the patients suddenly.... The os sterni is usually pointed to as the seat of this malady ... and sometimes there is with it a pain about the middle of the left arm. The usual cause of myocardial ischaemia is coronary atherosclerosis. Other diseases of the coronary arteries (emboli, spasm, vasculitis, Kawasaki disease, congenital anomalies), other cardiac diseases (hypertrophic cardiomyopathy, severe hypertension, severe aortic valve disease), and high output states (severe anaemia, thyrotoxicosis) are all uncommon or rare causes of angina. However, while angina is usually associated with atherosclerotic coronary artery disease, the converse is not always true. The condition of coronary atherosclerosis is very common (fatty streaks and more advanced plaques are almost universal in adults in industrialised countries) but it does not always cause myocardial ischaemia. Furthermore, myocardial ischaemia may present other than with angina - for each presentation there is a wide differential diagnosis.
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PMID:Clinical presentation and diagnosis of coronary artery disease: stable angina. 1175 1

Cardiovascular disease (CVD) is the major cause of death in renal transplant recipients (RTR). Several cohort studies have examined CVD in RTR, but none have addressed the development of congestive heart failure (CHF). CHF would hypothetically be a frequent and prognostically important event in RTR. A retrolective cohort study was, therefore, conducted in two Canadian centers to describe the incidence, risk factors for, and interrelationships between de novo CHF, de novo ischemic heart disease (IHD), and mortality in 638 consecutive adult RTR who were free of cardiac disease at 1 yr posttransplant. Detailed clinic and hospital records were available for 99% of patients. Median follow-up was 7 yr (range, 1 to 28 yr). De novo CHF occurred as frequently as de novo IHD (1.26 versus 1.22 events/100 patient-years, respectively) and appeared to carry a similar prognosis (relative risk for death, 1.78 [confidence interval, 1.21 to 2.61] for CHF versus 1.50 [1.05 to 2.13] for IHD). The incidence of CHF was considerably higher than that in the Framingham cohort, whereas the incidence of IHD was not, suggesting that renal transplantation might correspond more to a state of "accelerated heart failure" than to "accelerated atherosclerosis." Age, diabetes, gender, BP, and anemia were identified as independent risk factors for de novo CHF, whereas age, diabetes, gender, BP, and rejection were independent risk factors for de novo IHD. Optimal strategies for treatment of BP and anemia in RTR will need to be determined in randomized controlled trials.
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PMID:Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. 1191 70

Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated compounds, and antioxidant defense mechanisms. Most reports prove that oxidative stress is present in ESRD patients. Several studies tend to accreditate the hypothesis by which oxidative stress is a strong co-factor for the development of complications related to long-term HD such as atherosclerosis, amyloidosis, malnutrition, anemia, and infection. In order to evaluate the rationale for curative action against oxidative damage in chronic renal failure patients, we reviewed the putative factors involved in this process. Antioxidant systems are severely impaired in uremic patients and gradually altered with the degree of renal failure. Moreover, the inflammatory state caused by the hemoincompatibility of the dialysis system plays a critical role in the activation of NADPH oxidase, aggravating the pro-oxidant status of uremic patients. Prevention of ROS overproduction by improvement of dialysis biocompatibility, an important component of adequate dialysis, might be completed by antioxidant supplementation.
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PMID:Oxidative stress in hemodialysis patients: is NADPH oxidase complex the culprit? 1198 24


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