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

The anaemia of chronic kidney disease (CKD) is efficiently corrected with a combination of recombinant erythropoietin (rhEPO) and intravenous iron supplementation. Recently, patients with severe cardiac failure and anaemia have also been shown to benefit from this treatment. However, iron excess may lead to the production of free radicals and has been incriminated in the pathogenesis of atherosclerosis and increased risk of infection, the two major causes of death in end-stage renal disease. The exact risk of excess iron supplementation has not been defined and, in the absence of sensitive and specific indicators of iron overload, the risk remains difficult to quantify. There is increasing epidemiological evidence incriminating iron overload as a risk factor in CKD, but direct evidence is still hard to obtain. The precise role of iron is complicated further by the complex inter-relationships between iron metabolism and the inflammatory process characteristic of CKD. The recent discovery of the antimicrobial peptide, hepcidin, may shed light on these inter-relationships. New methods for quantifying non-transferrin-bound (or labile plasma) iron may help in the future to identify patients at risk for toxicity from excess iron supplementation.
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PMID:Intravenous iron supplementation in the anaemia of renal and cardiac failure--a double-edged sword? 1602 27

In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non-transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with caution but its use should not be feared whenever indicated.
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PMID:Intravenous iron therapy: well-tolerated, yet not harmless. 1628 58

Endothelial dysfunction (ED) in peritoneal dialysis patients plays pivotal role in progression of atherosclerosis and hemostasis disturbances. Malnutrition is one of the most important complication of PD. Both ED and malnutrition cause higher rate of cardiovascular events in these patients. 32 PD patients were analyzed. Endothelial function was assessed by measurements of serum level of vWF:Ag; t-Pa:Ag; TM:Ag. Nutritional status assessment included: body mass index-BMI, MAMC measurements; and serum albumin, total protein, prealbumin, transferrin, cholesterol, insulin, insulin like growth factor-1 (IGF-1). There were higher levels of vWF:Ag but lower of t-PA:Ag and TM:Ag after 12 month of observation. Serum levels of prealbumin, insulin, cholesterol were stable, but there were lower levels of albumin, IGF-1, and higher of transferrin at the end of the follow up. There were no differences in anthropometric indices during the follow up. We found statistically significant linear correlations: t-Pa:Ag vs prealbumin; t-Pa:Ag vs cholesterol; TM:Ag vs albumin. In the course of 12 months observation of peritoneal dialysis patients we found deterioration of endothelial function, expressed by evaluated endothelial antigens. Some correlations found in our study might express close relationship between endothelial function markers and nutritional status.
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PMID:[Endothelial dysfunction in peritoneal dialysis patients and its relationship to nutrition]. 1714 96

Iron could promote free radical formation, which may lead to injury of the arterial wall and atherosclerosis. Blood donation may reduce cardiovascular risk by lowering body iron status. We collected data on blood donation history and intima-media thickness of the common carotid artery (CIMT) in 819 subjects (50-70 years), who were recruited from municipal and blood bank registries in The Netherlands. Serum iron parameters were assessed, including non-transferrin bound iron (NTBI) that has recently been found in conditions of iron overload. Serum ferritin was lower in current donors (n=443; 44 microg/L) than in ex-donors (n=120; 114 microg/L) and never-donors (n=256; 124 microg/L, P for trend <0.001). For NTBI, values were 2.33, 2.54, and 2.51 micromol/L, respectively (P<0.05). CIMT was slightly reduced in frequent donors (i.e., > or =49 times during life or > or =2 times per year), although not statistically significant. CIMT was not significantly related to NTBI. Frequent blood donation, resulting in lowered body iron, might give some protection against accelerated atherosclerosis.
Atherosclerosis 2008 Feb
PMID:Blood donation, body iron status and carotid intima-media thickness. 1733 86

Intravenous iron is widely used to maintain adequate iron stores and prevent iron deficiency anemia in patients with chronic kidney disease, yet concerns remain about its long-term safety with respect to oxidative stress, kidney injury, and accelerated atherosclerosis, which are the subjects of this review. Three parenteral iron formulations are available for use in the United States: Iron dextran, iron gluconate, and iron sucrose. Iron dextran, especially the high molecular form, has been linked with anaphylactoid and anaphylactic reactions, and its use has been declining. A portion of intravenous iron preparations is redox-active, labile iron available for direct donation to transferrin. In vitro tests show that commonly available intravenous iron formulations have differing capacities to saturate transferrin directly: Iron gluconate > iron sucrose > iron dextran. Intravenous iron treatment produces oxidative stress, as demonstrated by increases in plasma levels of lipid peroxidation products (malondialdehyde), at a point that is much earlier than the time to peak concentration of catalytically active iron, suggesting a direct effect of iron sucrose on oxidative stress. Furthermore, iron sucrose infusion produces endothelial dysfunction that seems to peak earlier than the serum level of free iron. Intravenous iron sucrose infusion also has been shown to produce acute renal injury and inflammation as demonstrated by increased urinary albumin, enzyme (N-acetyl-beta-glucosaminidase), and cytokine (chemokine monocyte chemoattractant protein-1) excretions. Although the long-term dangers of intravenous iron are unproved, these data call for examination of effects of intravenous iron on the potential for long-term harm in patients with chronic kidney disease.
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PMID:Acute injury with intravenous iron and concerns regarding long-term safety. 1769 72

Transferrin is a plasma protein with the primary role of transporting iron through the body and delivering it to the cells that utilize it. Because free ionic iron is very toxic by creating free radicals, the importance of transferrin lies in its antioxidant properties. Atherosclerosis, a pathological process affecting arterial walls, is a chronic inflammatory response in which oxidative stress caused by free radicals is a key factor in its pathogenesis. We postulate therefore that the plasma protein transferrin acts protectively in these events, by holding iron in containment and reducing oxidative stress. Furthermore, it is possible that a disturbance in transferrin function and homeostasis is a direct factor triggering and exacerbating atherosclerosis. Decreased transferrin levels, increased transferrin saturation, defective transferrin binding of iron, or other disorders may lead to increased oxidative stress and lipid peroxidation involved in the pathology of atherosclerosis. Some oxidative stress-related diseases have been linked to such systemic transferrin abnormalities, and we hypothesize that similar disruptions could account for an unfavorable microenviroment in the evolvement of atherosclerotic plaques. If confirmed, this proposed mechanism would significantly improve our understanding of the disease.
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PMID:The role of transferrin in atherosclerosis. 1795 19

Epidemiological studies and experimental data suggest iron involvement in atherosclerosis. The relation between iron and atherosclerosis is complex and remains contradictory. In thalassemia patients, non transferrin bound iron (NTBI) and free hemoglobin (Hb) are present in plasma and may accelerate atherogenesis, but its progression may be inhibited by iron chelators. The mechanism whereby iron may stimulate atherogenesis has been intensively investigated. Non transferrin bound iron and sera from subjects with hemochromatosis induced endothelial activation with expression of vascular adhesion molecules and endothelial inflammatory chemokines. Such events could be inhibited by iron chelators and oxygen radical scavengers with intracellular activity. Iron chelators may be effective in preventing vascular damage in patients with high concentrations of NTBI as found in thalassemia.
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PMID:Can iron chelators influence the progression of atherosclerosis? 1827 90

Cardiovascular disease caused by accelerated atherosclerosis is the major determinant of morbidity and mortality in chronic kidney disease patients. Vitamin D and its analogs provide survival benefit for hemodialysis (HD) patients. Vitamin D exerts its effects through the vitamin D receptor (VDR) that is coded for by a gene showing several polymorphisms that, in turn, are associated with a variety of diseases and differential responses to vitamin D. In this study, we evaluated the association between 4 VDR polymorphisms (ie, those identified by the restriction enzymes BsmI, ApaI, TaqI, and FokI) and iron indices (serum iron, transferrin, transferrin saturation, and ferritin) in 88 hemodialysis patients routinely treated with vitamin D. The absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f, respectively. Our results show that in HD patients with transferrin saturation <20%, the F allele was more frequent than in HD patients with transferrin saturation >20% (P = .03). This relationship may provide a link between VDR alleles and iron and nutritional markers, which are highly predictive variables of cardiovascular morbidity and mortality in hemodialysis patients.
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PMID:Iron indices and vitamin D receptor polymorphisms in hemodialysis patients. 1833 45

Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.
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PMID:Relationship between serum nickel and homocysteine concentration in hemodialysis patients. 1846 90

Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups. We examined cardiovascular disease risk factors and iron and liver biomarkers, as well as morbidity and mortality associated with the C282Y and H63D variants of HFE in the Atherosclerosis Risk in Communities (ARIC) study, which is a population-based cohort of nearly 16,000 U.S. white and black men and women who were 45-64 years old at baseline. Subjects were followed for an average of 15 years for death, incident coronary heart disease, stroke, and heart failure, and an average of 8 years for incident diabetes. The prevalence of C282Y homozygosity was 0.42% (45/10,800) in whites, which is similar to other North American population-based studies. C282Y homozygotes had significantly lower mean low-density lipoprotein (LDL) cholesterol and fibrinogen as well as higher mean levels of iron (ferritin, transferrin saturation) and liver biomarkers (alanine aminotransferase, Hepascore) compared with HFE wild-type subjects. Rates of all-cause mortality, cardiovascular disease, and diabetes were similar across HFE genotypes. These prospective, population-based data indicate higher serum iron indices and possible mild liver dysfunction or disease in some C282Y homozygotes, but they provide little evidence that HFE C282Y or H63D mutations are related to all-cause mortality, cardiovascular disease, or diabetes. Reduced LDL in C282Y homozygotes may be because of effects of excess iron on cholesterol metabolism and lipoprotein formation in the liver.
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PMID:HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study. 1859 31


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