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

Although it is frequently stated that "atherosclerosis begins in childhood," it is not so frequently stated that only the first stage of atherosclerosis--the innocuous, highly reversible fatty streak--occurs in childhood. The more harmful second stage of atherosclerosis, the atheromatous plaque, does not appear until after puberty in boys and much later in girls. The purpose of this review is to emphasize the natural history of atherosclerosis, particularly as it pertains to children, and to consider its implications for the prevention of atherosclerosis. Present evidence supports the view that intervening in childhood (2-15 years) with low-fat, low-cholesterol diets or even worse, lipid-lowering drugs, to prevent plaque formation in adulthood is wasted effort. Furthermore, the data show that children respond more poorly to lipid-lowering diets than do adults, and that the emphasis on low-fat diets for children leads some parents to overdo the guidelines and unwittingly push their children into malnutrition. The program adopted by Health Canada on the advice of pediatricians in that country to taper fat intake from 40% of energy at 2 years of age to 30% of energy at the conclusion of linear growth (late adolescence) is a step forward.
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PMID:Atherogenesis in children: implications for the prevention of atherosclerosis. 1095 40

Despite the improvements in dialysis technology, the cardiovascular mortality rate is still unacceptably high among dialysis patients. It is obvious that traditional risk factors, such as hypertension, chronic heart failure (CHF), dyslipidemia and diabetes mellitus, may account for a large part of the increased cardiovascular mortality rate in these patients. However, based on recent research it could be speculated that other, non-traditional risk factors might also contribute to the high cardiovascular mortality rate in dialysis patients. Chronic inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature in dialysis patients and is associated with an increased cardiovascular morbidity and mortality. Indeed, elevated levels of pro-inflammatory cytokines (such as TNF-alpha, IL-1 and IL-6) may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms, which will be discussed in this review. Based on the strong associations observed between malnutrition, inflammation and atherosclerosis in patients with chronic renal failure (CRF) we have proposed that these features constitute a specific syndrome (MIA), which carries a high mortality rate. As elevated levels of pro-inflammatory cytokines may play a central part in the vicious circle of malnutrition, inflammation and atherosclerosis, further research is needed to investigate whether or not different anti-cytokine treatment strategies may improve survival in dialysis patients.
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PMID:Inflammatory and atherosclerotic interactions in the depleted uremic patient. 1111 78

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

Insulin resistance is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population. Insulin action is the consequence of insulin binding to its plasma membrane receptor and is transmitted through the cell by a series of protein-protein interactions. Two major cascades of protein-protein interactions mediate intracellular insulin action: one pathway is involved in regulating intermediary metabolism and the other plays a role in controlling growth processes and mitoses. The regulation of these two distinct pathways can be dissociated. Indeed, some data suggest that the pathway regulating intermediary metabolism is diminished in type 2 diabetes while that regulating growth processes and mitoses is normal.--Several mechanisms have been proposed as possible causes underlying the development of insulin resistance and the insulin resistance syndrome. These include: (1) genetic abnormalities of one or more proteins of the insulin action cascade (2) fetal malnutrition (3) increases in visceral adiposity. Insulin resistance occurs as part of a cluster of cardiovascular-metabolic abnormalities commonly referred to as "The Insulin Resistance Syndrome" or "The Metabolic Syndrome". This cluster of abnormalities may lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension or polycystic ovarian syndrome depending on the genetic background of the individual developing the insulin resistance.--In this context, we need to consider whether insulin resistance should be defined as a disease entity which needs to be diagnosed and treated with specific drugs to improve insulin action.
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PMID:Insulin resistance: definition and consequences. 1146 May 65

Cardiac valve calcification (VC) has long been regarded as a consequence of aging and abnormal calcium-phosphate metabolism in uremic patients. In view of the recent recognition of association among inflammation, malnutrition, and atherosclerosis, the possible role of inflammation and malnutrition in VC was investigated. Inflammatory markers (including C-reactive protein [CRP], fibrinogen, and basal metabolic rate) and nutritional status (assessed using serum albumin, subjective global nutrition assessment, and handgrip strength) were examined, in addition to calcium phosphate parameters and other traditional cardiovascular risk factors, including gender, smoking habits, BP, and lipid profile, in relation to VC in 137 patients who were on continuous ambulatory peritoneal dialysis. Compared with patients with no VC, patients with VC not only were older (60 [10] versus 54 [12] yr; P = 0.005), had higher plasma phosphate (1.89 [0.52] versus 1.64 [0.41] mmol/L; P = 0.003), and had higher parathyroid hormone (83 [40, 145] versus 38 [16, 71] pmol/L; P = 0.001) but also had higher CRP (4.5 [0.1, 13.4] versus 0.2 [0.1, 4.4] mg/L; P = 0.004), had higher fibrinogen (6.6 [1.9] versus 5.7 [1.3] g/L; P = 0.002), and had lower serum albumin (26 [4] versus 29 [3] g/L; P = 0004). Twenty-three percent of patients with VC versus 17% of patients with no VC were moderately to severely malnourished according to subjective global nutrition assessment (P = 0.05). Even after adjustment for patients' age, duration of continuous ambulatory peritoneal dialysis, diabetes, and calcium x phosphate product, cardiac VC remained strongly associated with CRP (odds ratio, 1.05; P = 0.026) and albumin (odds ratio, 0.85; P = 0.01). The data suggest that VC not only is a passive degenerative process but also involves active inflammation, similar to that seen in atherosclerosis. The presence of uncontrolled hyperphosphatemia and hyperparathyroidism further accelerates the progression of calcification. The data also indicate that VC and atherosclerosis should be considered as associated syndromes, sharing similar pathogenic mechanisms, namely active inflammation.
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PMID:Association of inflammation and malnutrition with cardiac valve calcification in continuous ambulatory peritoneal dialysis patients. 1151 87

Plasminogen activator (PA) inhibitor-1 (PAI-1) has been recognized as a surrogate marker of endothelial dysfunction in diseases associated with impaired angiogenesis, including atherosclerosis, diabetic vasculopathy, and nephropathy. To establish the necessary and sufficient components of the PA system [PAI-1, urokinase-type PA (uPA), or tissue-type PA (tPA), and plasminogen (Plg)] for angiogenesis, we examined angiogenic competence of vascular explant cultures obtained from mice deficient in PAI-1, tPA, uPA, and Plg. To gain insight into the requirement for different matrix-degrading systems during endothelial cell migration across plasmin-degradable basement membranes compared with profibrotic areas containing plasmin-nondegradable collagen, we contrasted vascular sprouting in collagen with Matrigel lattices. PAI-1(-/-) vessels showed an increased capillary sprouting in both collagen and Matrigel. Deficiency of uPA significantly reduced the rate of sprouting, whereas tPA(-/-) vessels showed a profound inhibition of capillary sprouting. The Plg(-/-) vessels failed to sprout, a defect that was restored not only by exogenous Plg, but also by the addition of PAs; a nonproteolytic effect of tPA was observed in Matrigel. Zymography revealed no differences in the activity of metalloproteinase (MMP)-2 and -9 in wild-type and PAI-1(-/-) vessels, but demonstrated reduced MMP-9 activity in all angiogenesis-deficient vessels. In summary, 1) PAI-1 by itself is a modest inhibitor of endothelial sprouting, 2) tPA and Plg are indispensable for angiogenesis in this model, 3) Plg is not the only substrate for PAs, and 4) the activity of MMP-9 is undetectable in explant cultures from tPA and Plg knockout mice.
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PMID:Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis. 1155 72

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

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

Recent clinical evidence has indicated that the level of soluble ICAM-1 (sICAM-1) is correlated with the severity of atherosclerosis and can predict future cardiovascular events. Here, using apolipoprotein E (APOE)-deficient mice, we investigated the level of sICAM-1 in parallel with endothelial ICAM-1 expression and aortic atherosclerosis. We also examined the effect of ICAM-1 deficiency during the progression of atherosclerosis using double knockout mice. The level of sICAM-1 increased significantly in parallel with the progression of atherosclerosis in APOE-deficient mice, while the sICAM-1 level remained constant in wild-type mice from 3 to 10 months of age. ICAM-1 staining was detected in virtually all endothelial cells, however, ICAM-1 was expressed strongly in the endothelium overlying atheromatous palque in APOE-deficient mice. Deficiency of ICAM-1 in APOE-deficient mice significantly reduced lesions after 5 and 10 months. The present study supported the notion that the level of sICAM-1 is closely related with the severity of atherosclerosis and cardiovascular events, and also suggested that inhibition of ICAM-1 can delay the progression of atherosclerosis.
Atherosclerosis 2002 Feb
PMID:Involvement of ICAM-1 in the progression of atherosclerosis in APOE-knockout mice. 1184 52

Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Hyperphosphatemia and an increased calcium-phosphate ion product have also been associated with an increased risk of death. Cardiovascular calcifications secondary to increases in phosphate and calcium load in dialysis patients might exert an important contribution to the excess cardiovascular mortality and morbidity in dialysis patients. Elevated serum levels of plasma C-reactive protein (CRP) are associated with the extent and severity of the atherosclerotic processes as well as with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. In patients affected by pre-dialytic renal failure increased levels of CRP and IL-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation--even in the predialytic phase of renal failure--of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could be at least in part due to the dialytic technique. We have shown that the increase of CRP in stable dialysis patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants. During conventional dialysis, a positive calcium balance and a concomitant inflammatory state may act as cofactors in the development of cardiovascular calcifications. We suggest that this hypothesis should be verified by clinical studies. A reevaluation of the ideal calcium levels in the dialysate is warranted: a neutral intradialytic calcium balance is probably more appropriate, although not easily attainable.
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PMID:Vascular calcifications as a footprint of increased calcium load and chronic inflammation in uremic patients: a need for a neutral calcium balance during hemodialysis? 1185 66


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