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

Cholesterol embolic disease is a devastating complication of atherosclerosis. Universally recommended treatment is lacking thus far. Recent data suggest that a therapeutic protocol aimed at specifically combating three causes of mortality, recurrent bouts of cholesterol embolism, cardiac failure, and cahexia, were associated with a favorable clinical outcome. As for drug therapy, corticosteroid has been reported to be beneficial in reducing local and general inflammatory responses. Concerning apheresis, combined therapy consisting of plasma exchange and low to intermediate-dose corticosteroid therapy has been shown to be effective in multivisceral cholesterol embolism. Low density lipoprotein (LDL) apheresis has been reported to be beneficial for cholesterol embolism-induced damage to the skin and brain.
Ther Apher Dial 2003 Aug
PMID:Apheresis in the treatment of cholesterol embolic disease. 1288 28

Hypercholesterolemia affects not only the coronary artery, but also the aortic root, particularly the aortic valve. Aortic stenosis is critical in the prognosis for most patients with homozygous familial hypercholesterolemia (FH) and some heterozygous FH patients who result in aortic valve replacement (AVR). Histopathological examination of their valves shows lipid deposition, inflammatory cell infiltration and calcification in the aortic cusps. These pathological findings are common in non-FH patients with AVR. In homozygous FH patients, the aortic valves are injured by extreme hypercholesterolemia in a relatively short period of time, whereas in heterozygous FH patients with additional risk factors, the damage to the valves occurs over an intermediate time period. In the non-FH population with several risk factors, an underlying raised serum cholesterol level results in gradual impairment over a number of years. Aortic valvular dysfunction caused by hypercholesterolemia, which we termed hypercholesterolemic valvulopathy is recognized to be a life-threatening complication as the primary clinical characteristic of malignant atherosclerosis.
Ther Apher Dial 2003 Aug
PMID:Hypercholesterolemic valvulopathy: an aspect of malignant atherosclerosis. 1288 29

Homozygous familial hypercholesterolemia (FH) and heterozygous FH, with or without elevation of Lp(a), or isolated massive elevation of Lp(a) with clinically relevant coronary heart disease are indications for low-density lipoprotein (LDL) apheresis, as long as maximal conventional lipid lowering drug therapy does not lead to a LDL cholesterol level below 100 mg/dL. Reduction of lipoproteins and Lp(a), of oxidation of LDL, improvement of disturbed vasomotion, the procoagulatory state and disturbed hemorheology associated with atherosclerosis, as well as the stabilization of plaques and the decrease of cytokines and adhesion molecules have been induced by apheresis and are thought to favorably influence regression of artherosclerosis. Several intervention studies point in this direction.
Ther Apher Dial 2003 Jun
PMID:Indication of low-density lipoprotein apheresis in severe hypercholesterolemia and its atherosclerotic vascular complications: dextran sulfate cellulose low-density lipoprotein apheresis. 1292 11

Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) is a selective and careful apheresis procedure. Through the application of heparin and lowering the pH value, lipoproteins and fibrinogen are reduced by 50-60%. In addition, adhesion molecules (ICAM-1, VCAM-1, p-selectin) which play a key role in the development and progression of atherosclerosis, are also markedly reduced. A PET scan performed 20 h after LDL apheresis shows the improvement of coronary vasodilation capacity. This is supposed to be mainly due to the marked reduction of LDL cholesterol and fibrinogen with consecutive improvement of endothelial dysfunction and rheology.
Ther Apher Dial 2003 Jun
PMID:Heparin-induced extracorporeal low-density lipoprotein precipitation. 1292 14

End-stage renal disease (ESRD) is characterized by a high mortality rate, which is mainly caused by cardiovascular disease. In patients with ESRD, high levels of pro-inflammatory cytokines and increased oxidative stress are common features and may contribute to the development of malnutrition, anaemia, resistance to recombinant human erythropoietin (epoetin) and atherosclerosis. The onset of inflammation is multi-factorial and is a predictor of poor outcome in ESRD. Although the inflammation may reflect the underlying cardiovascular disease, the acute-phase response may also contribute to both oxidative stress and progressive vascular injury. The acute-phase response in these patients may be influenced by a number of factors, and possibly the dialysis procedure itself. Inflammation and the acute-phase response interact with the haematopoietic system at several levels, resulting in reduced erythropoiesis, accelerated destruction of erythrocytes and blunting of the reactive increase in erythropoietin in response to reduced haemoglobin levels. In patients with ESRD, epoetin resistance has been linked with inflammation, which is often associated with a state of functional iron deficiency. Patients with ESRD are thought to have a reduced capacity in their control of oxidative stress and there is evidence that suggests that a relationship may exist between inflammation, oxidative stress and the treatment of anaemia with epoetin. Controlled trials are needed before evidence-based recommendations for the management of inflammation-induced anaemia and resistance to epoetin can be defined.
Nephrol Dial Transplant 2003 Nov
PMID:Anaemia and inflammation: what are the implications for the nephrologist? 1460 95

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.
Adv Perit Dial 2003
PMID:Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients. 1476 71

Nitric oxide (NO), previously thought of as a noxious gas, is now recognized as an important mediator of vascular responsiveness. Soon after its discovery, it was realized that the actions of NO are similar to the previously described endothelium-derived relaxing factor (EDRF). It is synthesized in the vascular endothelium utilizing the enzyme nitric oxide synthase (NOS) and diffuses in the adjacent vascular media, where it has a vasodilatory action. Opposing actions of NO and vasoconstrictor agents (such as endothelin-1, angiotensin IotaIota, and others) maintain the vascular tone of the renal arteries. The same balance at the level of the macula densa maintains glomerular filtration rate (GFR) during varying levels of salt excretion. Lack of NO can result in disruption of this fine balance, with resultant vasoconstriction and disease progression, hypertension, and accelerated atherosclerosis. In addition, hypertension may result from positive salt balance that occurs when macula densa NOS is inhibited. While most investigators report low levels of NO in uremic subjects, the levels in hemodialysis (HD) patients have not been characterized adequately. This is primarily because HD patients are exposed to both stimulatory and inhibitory factors for NO synthesis. Retention of inhibitors of NOS tends to decrease NO levels, whereas production of NO will be increased by cytokines generated during blood-dialyzer interaction. There is less disagreement, however, over the finding of elevated levels in those with dialyzer reactions and dialysis-induced hypotension. Recent developments in the isolation of inducible and constitutive forms of NOS makes understanding of its pathophysiologic effects more complete. Newer treatment directed at inhibiting only the inducible forms of NOS (sparing the constitutive forms) may soon be found useful for the treatment and prevention of hypotension and dialyzer reactions in HD patients.
Semin Dial
PMID:Nitric oxide and hemodialysis. 1514 49

The association of high body mass index (BMI) with better survival in chronic kidney disease (CKD) is considered a "risk factor paradox" or "reverse epidemiology." Since malnutrition is a powerful predictor of death and cardiovascular disease is its leading cause, it has been suggested that malnutrition and atherosclerosis must be associated. Thus the current paradigm is that malnutrition is a risk factor for atherosclerosis and obesity is protective in CKD patients. We recently showed that high-BMI patients with inferred high body fat have an increased prevalence of atherosclerosis and subsequent cardiovascular and all-cause mortality. Prior cross-sectional studies also showed that high BMI in CKD is associated with higher C-reactive protein (CRP) levels and increased coronary calcification on electron beam computed tomography (CT) scan. These apparently conflicting data on better survival but increased inflammation and atherosclerosis in high-BMI CKD patients could be explained as follows. It is hypothesized that nutrition exerts a much stronger influence on survival than atherosclerosis in CKD. Malnutrition strongly augments the hazard of death from coexistent diseases, while better nutrition has the opposite effect. Thus the risk of death is highest in malnourished patients (low muscle and low fat mass) and lowest in well-nourished patients (high BMI, high muscle mass). Obesity (high BMI, high fat mass) is associated with inflammation and atherosclerosis. The risk of death from obesity and atherosclerosis is increased, but not so much as occurs with malnutrition. Therefore high body fat patients have intermediate survival. Thus it is postulated that an association of obesity, inflammation, and atherosclerosis (OIA syndrome) might exist in CKD.
Semin Dial
PMID:The body mass index paradox and an obesity, inflammation, and atherosclerosis syndrome in chronic kidney disease. 1514 50

Familial hypercholesterolemia is an autosomal-dominant inherited disorder caused by mutations in the low-density lipoprotein (LDL) receptor gene. The homozygous form is characterized by high-serum LDL cholesterol concentrations, xanthoma formation and premature atherosclerosis. Recently, another molecular defect that also results in severely elevated LDL cholesterol levels was identified: autosomal recessive hypercholesterolemia. This inherited disorder is caused by a mutation in a putative LDL receptor adaptor protein. In our lipid clinic, three sisters with phenotypic homozygous hypercholesterolemia were recently diagnosed as having autosomal recessive hypercholesterolemia. They presented in 1990 with massive tuberous xanthomas at the knees, thighs, elbows and buttocks. LDL receptor and apolipoprotein B gene defects were excluded through mutation analysis. From 1992 onward they underwent LDL-apheresis on a weekly basis. To date the clinical outcome is very satisfying with no evidence of coronary heart disease or aortic valve lesions and almost complete regression of xanthomatosis.
Ther Apher Dial 2004 Aug
PMID:Autosomal recessive hypercholesterolemia in three sisters with phenotypic homozygous familial hypercholesterolemia: diagnostic and therapeutic procedures. 1527 77

The uraemic syndrome is a complex condition that results from the retention of "waste" compounds that normally would be excreted into the urine or catabolized by the kidneys. In addition, inflammation has been implicated in symptoms associated with uraemia, including its role in the malnutrition-inflammation-atherosclerosis syndrome. Regarding vascular disease, traditional risk factors such as hypertension and gender do not seem to have the same significance in the uraemic population compared with patients without renal failure, and so the possibility has been raised that the uraemic toxins that result in the uraemic syndrome could play a role in this process. In this review, various questions are addressed regarding the involvement of cytokines in uraemia and the effects of dialysis membranes and fluids in patients receiving haemodialysis or peritoneal dialysis on cytokine levels. The effects of non-dialysis-related factors on levels of cytokines, mortality rates and other uraemic disorders are also discussed. It is concluded that cytokines are undoubtedly retained in uraemia, and that the loss of renal excretion almost certainly plays a key role in this process. Many cytokines have a pro-inflammatory role, probably resulting in a number of clinical events that are related to the increased morbidity and mortality of uraemic and haemodialysis patients. Any adjustment of the subtle balance between pro- and anti-inflammation by medical interventions should be conducted carefully because of an enhanced risk of serious infectious episodes. Bioincompatibility of dialysis techniques probably enhances the generation of cytokines as well as other uraemic toxins.
Nephrol Dial Transplant 2004 Aug
PMID:Interleukin/cytokine profiles in haemodialysis and in continuous peritoneal dialysis. 1528 59


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