Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular risk in the dialysis population is exceedingly high, and there is now convincing evidence that inflammation is strongly linked to atherosclerosis in this population. The source of inflammation in dialysis patients still remains undefined. Bacterial contamination during the extracorporeal circulation and bioincompatibility explain only a very small part of the high prevalence of inflammation [as defined by raised C-reactive protein (CRP)] in these patients. In the general population, several infectious agents have been implicated as likely culprits of atherosclerosis, and Chlamydia pneumoniae is the most suspected. In dialysis patients, the presence of a high titre of anti-C. pneumoniae antibodies is associated with the severity of atherosclerosis. The CREED database (Cardiovascular Risk Extended Evaluation in Dialysis patients) has on file 278 patients tested for C. pneumoniae and followed-up for 4 years. Interestingly, in this database, the risk for cardiovascular death is approximately 4 times higher in the group of patients (n=50) seropositive for Chlamydia and with raised CRP than in those with no evidence of Chlamydia infection and normal CRP. Yet seropositivity to Chlamydia did not significantly increase the risk associated with raised CRP. These data suggest that raised CRP and C. pneumoniae seropositivity is a high risk situation, but it remains very uncertain as to whether Chlamydia infection per se contributes to the high cardiovascular risk of dialysis patients.
Nephrol Dial Transplant 2002
PMID:Atherosclerosis in dialysis patients: does Chlamydia pneumoniae infection contribute to cardiovascular damage? 1214 73

Inflammation is thought to play a central role in the aetiology and outcome of atherosclerosis. C-reactive protein (CRP) is a prominent product of the inflammatory response syndrome and a marker of overall and cardiovascular death in the general population and in dialysis patients. CRP is 5- to 10-fold higher in haemodialysis patients than in healthy controls and clearly is multifactorial in origin. A number of endogenous factors have been identified in vitro [angiotensin II, lipopolysacharide, modified low-density lipoprotein (LDL), advanced glycation end-products, homocysteine, viral infections] which all are able to trigger a nuclear factor (NF)-kappaB-mediated inflammatory, interleukin-6-driven, response via the generation of oxygen free radicals (oxidative stress). In addition, exogenous factors (dialysate endotoxin, vascular access, cuprophane dialyser material) have been identified in clinical studies which are also responsible, at least in part, for high serum CRP levels. Some of these factors function by themselves as non-traditional cardiovascular risk factors. Whether CRP is simply a marker of cardiovascular disease and mortality or whether it is in the causal pathway of the disease remains an open question. Recent data are in favour of a direct involvement in the pathogenesis of disease, since binding of CRP to degraded LDL enhances complement activation and induces the expression of tissue factor.
Nephrol Dial Transplant 2002
PMID:C-reactive protein a marker for all-cause and cardiovascular mortality in haemodialysis patients. 1254 10

End-stage renal disease (ESRD) is characterized by an exceptional mortality rate, much of which is the result of cardiovascular disease (CVD). Although traditional risk factors are common in ESRD patients, they may not be sufficient alone to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is observed commonly in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury by several pathogenetic mechanisms. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation and atherosclerosis (MIA) would improve survival in dialysis patients. Recent evidence has demonstrated strong associations between inflammation and both increased oxidative stress and endothelial dysfunction in ESRD patients. As there is as yet no recognized, or even proposed, treatment for ESRD patients with chronic inflammation, it would be of obvious interest to study the long-term effect of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as the outcome in these patients.
Nephrol Dial Transplant 2002
PMID:Inflammation in end-stage renal failure: could it be treated? 1254 10

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Although traditional risk factors are common in ESRD patients, they alone may not be sufficient to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor which is commonly observed in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury by several pathogenetic mechanisms. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. Recent evidence has demonstrated strong associations between inflammation and both increased oxidative stress and endothelial dysfunction in ESRD patients. As there is not yet any recognized, or even proposed, treatment for ESRD patients with chronic inflammation, it would be of obvious interest to study the long-term effect of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in these patients.
Semin Dial
PMID:Inflammation in end-stage renal disease: sources, consequences, and therapy. 1235 37

Epidemiological and clinical studies have shown that damage to large arteries contributes to the high cardiovascular mortality in patients with end-stage renal disease (ESRD). Atherosclerosis is the most frequent cause of arterial damage. Occlusive lesions from atherosclerotic plaques (calcification) decrease the conduit function of arteries and reduce the elasticity of capacitance arteries (stiffening), affecting their dampening function. Arterial calcification and aortic stiffness are independent predictors of cardiovascular risk in the general population, and independent predictors of all-cause and cardiovascular mortality in ESRD patients. Successful treatment to reduce blood pressure (BP) and reverse aortic stiffness has a significant, BP-independent effect on survival in ESRD patients. However, response to such treatment may be limited in patients with microinflammation and raised levels of C-reactive protein.
Nephrol Dial Transplant 2002
PMID:Impairment of arterial function in chronic renal disease: prognostic impact and therapeutic approach. 1238 50

The majority of patients starting dialysis already have signs of advanced atherosclerosis, and the risk factors for cardiovascular morbidity and mortality seen in patients with end-stage renal disease (ESRD) develop with the disease progression. Therefore, the predialysis period is the ideal time to start therapeutic interventions. Traditional risk factors alone may not adequately predict cardiovascular disease (CVD) outcome in patients with ESRD. Inflammation has been identified as playing a key role in atherosclerotic CVD. Pro-inflammatory cytokines are pivotal to the inflammation that is associated with malnutrition and atherosclerosis in ESRD. Malnutrition may worsen patient outcome by aggravating existing inflammation and heart failure, accelerating atherosclerosis and increasing susceptibility to infection. Atherosclerosis is itself a major risk factor for CVD mortality. Moreover, inflammation is associated with congestive heart failure. Strong associations between malnutrition, inflammation and atherosclerosis in this patient population suggest the presence of a syndrome we have called malnutrition, inflammation, and atherosclerosis (MIA), which is associated with an exceptionally high mortality rate.
Nephrol Dial Transplant 2002
PMID:The malnutrition, inflammation, and atherosclerosis (MIA) syndrome -- the heart of the matter. 1238 54

Inflammatory status is observed in patients with chronic renal failure (CRF). The relationship between oxygen free radical production and dialysis could play an important role in protein oxidation. Carbonyl protein plasma level is an important tool in the study of protein stress, and it is related to the arterial intima thickness in the atherosclerosis process. We studied protein oxidative stress in 21 peritoneal dialysis (PD) patients and 42 hemodialysis (HD) patients as compared with 32 undialyzed patients with CRF. Carbonyl protein plasma levels were measured in nanomoles per milligram protein by the ELISA method (Winterbourn et al). Dialysis patients had a higher protein carbonyl content than did CRF patients (0.1265 +/- 0.04 nmol/mg vs. 0.1594 +/- 0.03 nmol/mg, p < 0.0002). Patients on PD had a lower level than patients on HD (0.1452 +/- 0.03 nmol/mg vs. 0.1665 +/- 0.04, p < 0.004). Glucose administration in PD is known to be able to increase glucose degradation products (GDPs) and advanced glycosylation end-products (AGEs) with high carboxylic and oxidative stress. In our study, the carbonyl protein level was higher in HD patients than in PD patients, perhaps because more protein oxidative stress is associated with hemodialysis technique or because the PD patients had greater residual renal function.
Adv Perit Dial 2002
PMID:Protein oxidative stress in dialysis patients. 1240 79

Oxidized low-density lipoprotein (Ox-LDL) has been related with progression of atherosclerosis. Some studies reported increased Ox-LDL levels in hemodialysis (HD) patients. The levels of Ox-LDL in peritoneal dialysis (PD) patients have not yet been clarified. We measured Ox-LDL in PD patients and investigated the related factors. We measured plasma Ox-LDL, total cholesterol (TC), triglycerides (TG), and LDL-cholesterol (LDL-c) levels in 18 PD patients (mean age: 55.5 +/- 9.8 years; mean duration of dialysis: 2.7 +/- 1.4 years) and in 24 HD patients as controls. We compared Ox-LDL levels in patients with diabetes mellitus (DM) and ischemic heart disease (IHD). And we looked at the correlation between Ox-LDL levels and adequacy of PD. Levels of Ox-LDL were significantly higher in the PD patients (2.24 +/- 1.14 ng/microgram LDL protein) than in the HD patients (1.43 +/- 0.90 ng/microgram LDL protein), and other lipids were higher in the PD patients. The Ox-LDL did not correlate with other lipids. The Ox-LDL levels of the PD patients with DM or IHD were higher than those of non DM or non IHD patients. The adequacy of PD did not correlate with Ox-LDL. Patients on PD, especially those with DM or IHD, showed elevated Ox-LDL levels. Special attention should be paid to the level of Ox-LDL and atherosclerosis in PD patients.
Adv Perit Dial 2002
PMID:Correlation between oxidized low-density lipoprotein and other factors in patients on peritoneal dialysis. 1240 17

Atherosclerosis is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Oxidative stress plays a role in the pathogenesis of uremic atherosclerosis. Although antioxidant substances (vitamins A and E) are elevated in the plasma of dialysis patients, intracellular and clinical signs of hypovitaminosis are frequently found. Recently, the importance of vitamin/carrier complexes as a marker of vitamin bioavailability has been demonstrated. In the present study, we analyzed vitamin A and E bioavailability, measured as vitamin/carrier complexes, and the relationship of those measurements with clinical atherosclerosis status in PD patients. We studied 45 patients (15 men, 30 women), who were divided into four groups according to clinical atherosclerotic score (CAS). Five cases were scored as CAS grade 1 (low CAS); 9 as CAS-2; 18 as CAS-3; and 13 as CAS-4. Vitamins A and E and their carriers [prealbumin and retinol binding protein (vitamin A), and cholesterol and triglycerides (vitamin E)] were determined. Plasma levels of vitamin A were low in 5 patients, normal in 7 patients, and high in 33 patients. By correcting the values for the carrier levels, we created three groups: 24 patients showed low vitamin A/carrier complex (5 from the low plasma vitamin A group, 6 from the normal-value group, and 13 from the high-value group); 11 patients were in the group with normal vitamin A/carrier (1 from the normal plasma vitamin A group, and 10 from the high-value group); and 10 patients were in the group with high vitamin A/carrier. The vitamin A/carrier complex showed a statistically significant, negative linear correlation with CAS and with serum iron. Low vitamin E plasma levels were found in 1 patient, normal levels in 28 patients, and high levels in 16 patients. When those values were corrected using the carrier values, three groups were also created. The group with low vitamin E/carrier complex contained 24 patients (1 from the low-value group, 22 from the normal-value group, and 1 from the high-value group). The group with normal vitamin E/carrier complex contained 21 patients (15 from the group with high vitamin E values, and 6 from the normal-value group). By univariate logistic regression analysis, significant associations between CAS and vitamin E plasma levels, vitamin E/carrier, age, and serum albumin were found. In the multiple logistic regression analysis, we confirmed that vitamin E/carrier complex, age, and serum albumin showed independent associations with CAS, but not with vitamin-only plasma levels. Our results in PD patients show a vitamin/carrier complex disorder that results in elevated vitamin mobilization from pool and target cells. Our results and the findings of other researchers about intracellular vitamin A and E deficiencies may change the traditional concept of hypervitaminosis A and E in uremic patients.
Adv Perit Dial 2002
PMID:True deficiency of antioxidant vitamins E and A in dialysis patients. Relationship with clinical patterns of atherosclerosis. 1240 20

Anorexia and protein malnutrition, occasionally associated with obesity, are frequently observed in peritoneal dialysis (PD) patients. Both are recognized risk factors for cardiovascular (CV) morbidity and mortality. Leptin is produced by adipocytes and regulates body-fat mass through a satiety central effect. Leptin accumulates in the uremic state. We analyzed the relationship between plasma leptin levels, nutritional status, obesity, CV risk factors, and atherosclerosis in PD patients. Leptin was determined using a polyclonal antibody [radioimmunoassay: Linco Research, St. Louis, MO, U.S.A.]. The normal range was 1-7.8 ng/mL. We studied 38 PD patients. Mean leptin levels were 59.1 +/- 57.5 ng/mL (elevated in 32 patients). Women (n = 21) showed higher leptin levels than did men (80.4 +/- 60 ng/mL vs. 32.3 +/- 43.3 ng/mL, p < 0.01), in spite of both groups having a similar body mass index (BMI). A statistically significant direct correlation was found between leptin and BMI (r = 0.7, p < 0.01) and triceps skin-fold measurement (r = 0.77, p < 0.01). Leptin levels and renal creatinine clearance (CCr) showed no significant correlation. Independent of BMI, higher leptin levels were associated with parameters considered to be CV risk factors (Framingham study), such as serum triglycerides < 150 mg/dL (n = 29) as compared with > 150 mg/dL (44.2 +/- 53.2 ng/mL vs. 80 +/- 58.4 ng/mL, p < 0.05), cholesterol < 250 mg/dL (n = 28) as compared with > 250 mg/dL, (50 +/- 55.6 mg/dL vs. 84.7 +/- 57.7 mg/dL, p < 0.05), uric acid < 7 mg/dL (n = 28) as compared with > 7 mg/dL (47 +/- 53.7 mg/dL vs. 93.1 +/- 56.6 mg/dL, p < 0.05), and the presence or lack of presence of left ventricular hypertrophy [68.8 +/- 60 (n = 30) vs. 29.5 +/- 23.7 (n = 5), p < 0.05]. The patients were classified into two groups according to a clinical atherosclerosis score (CAS). Nineteen patients had low CAS scores, and they showed higher plasma leptin values than did the other patients (82.4 +/- 65.7 ng/mL vs 35.8 +/- 36.6 ng/mL, p < 0.05). Twelve patients with anorexia had lower leptin values than did patients with normal appetite (19.2 +/- 15.8 ng/mL vs. 91.3 +/- 58.8 ng/mL, p < 0.001). In non obese patients (BMI < 25 and CCr < 3 mL/min, n = 14), leptin had a statistically significant direct linear correlation with markers of nutrition, including albumin (r = 0.63, p < 0.05), transferrin (r = 0.4, p < 0.05), cholesterol (r = 0.65, p < 0.05), and triglycerides (r = 0.6, p < 0.05). Finally, plasma leptin levels were notably increased in the PD population, indicating increased production (possibly by chronic hyperinsulinism), or uremic retention, or both. By multivariate analysis, we confirmed the association between leptin levels and sex, leptin and BMI, and leptin levels > 40 ng/mL and sex and LVH. All of those features suggest that plasma leptin levels could be considered a marker of CV risk and food intake in non obese PD patients without inflammation.
Adv Perit Dial 2002
PMID:Leptin as a marker of nutrition and cardiovascular risk in peritoneal dialysis patients. 1240 21


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