UMLS:C0004153 - FACTA Search

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

Apolipoprotein (Apo) E has an important role in triglyceride (TG)-rich lipoprotein metabolism, and the genotype of Apo E is associated with premature coronary artery disease. Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) develop various abnormalities of lipid metabolism and are prone to develop accelerated atherosclerosis. To investigate the distribution of Apo E genotype, and to evaluate the influence of Apo E polymorphism on lipid metabolism in CAPD patients, we measured Apo E genotypes, serum lipid, and lipoprotein levels in 54 CAPD patients (M:F = 1:1). The most common genotype of Apo E in the CAPD patients was E 3/3, found in 68.5%. The frequencies of the other genotypes were E 2/3, found in 14.8%, and E 4/3, found in 16.7%. No genotypic differences in Apo E were seen in the patients with regard to the presence of diabetes, the level of parathyroid hormone, or the transport characteristics of the peritoneal membrane. When comparing lipid levels by Apo E genotype, the total cholesterol and TG levels of E 2/3 patients were significantly higher than those of E 3/3 or E 4/3 patients. The differences in high-density or low-density lipoprotein cholesterol levels by Apo E genotype were not significant. In comparing lipoprotein levels by Apo E genotype, the Apo B and lipoprotein (a) levels of E 2/3 patients were significantly lower than those of E 3/3 or E 4/3 patients. In conclusion, the Apo E 3/3 genotype seems to be the most common genotype in CAPD patients, and the Apo E 2/3 genotype appears to be associated with high cholesterol and TG levels. These results demonstrate the need for further prospective studies in these subjects aimed at elucidating the impact of genetic variation at the Apo E locus on the development of atherosclerosis.
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PMID:Influence of apolipoprotein E genotype on lipid and lipoprotein levels in continuous ambulatory peritoneal dialysis patients. 1068 11

Vascular calcification is a common feature in chronic dialysis patients, but their clinical significance is debated and the role of kidney transplantation (TP) in the natural history of their development has received scanty attention. We will describe a case of dramatic worsening of vascular calcifications during TP in a young patient in spite of early and successful parathyroidectomy (PTX), and will discuss other causes which might be putatively linked to vascular damage during the time of TP. A 37-year-old man on regular dialytic treatment (RDT) for 11 years, received his first cadaveric transplantation in January 1993. He underwent PTX 6 months after TP because of the lack of decreasing in parathyroid hormone values despite normal graft function. Although PTX was effective, a dramatic worsening was evident in large as well as in medium and small-sized arteries during the following three years of TP. In February 1997, few months after starting dialysis again because of the recurrence of his primary membranoproliferative glomerulonephritis (MPGN), the patient experienced myocardial infarction followed by aorto-coronary bypass (right coronary artery and anterior descending coronary artery) and leg "claudicatio". Though a role for parathyroid hormone in vascular disease has been commonly accepted, the case here reported clearly shows that blunting parathyroid gland activity may be unable to avoid the worsening of a process of vascular disease during the time of TP. Many other factors--linked to the time of TP--may be involved in vascular diseases, such as nephrotic syndrome, dyslipidemia, hypertension and drugs. In the case of our patient, a clear cut risk factor for his progressive atherosclerosis can be designated hyperlipidema and other disturbancies secondary to a nephrotic syndrome due to relapse of MPGN, together with persistent hypertension. This is the first case report in the English literature which clearly demonstrates that TP may add fuel to the fire of vascular disease also in young people and even in the absence of parathyroid hyperactivity, perhaps on the basis of a favorable genetic background. Furthermore, the history of our patient demonstrates that vascular calcifcation heralds major cardiovascular diseases.
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PMID:Dramatic worsening of vascular calcifications after kidney transplantation in spite of early parathyroidectomy. 1114 Aug 10

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

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 +/- 0.2 ng/ml) as compared with controls (1.5 +/- 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 +/- 0.2 ng/ml vs. polysulfone 3.8 +/- 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca x P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.
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PMID:Serum levels of macrophage colony-stimulating factor and aortic calcification in hemodialysis patients. 1179 63

Biological interactions between the bone and the blood vessels are gradually being clarified. To investigate the relationship between bone mineral density and atherosclerosis in hemodialysis patients, we examined the bone mineral density and the intima-media thickness of the carotid artery in 83 dialysis patients with non-diabetic nephropathy (44 men and 39 women) aged from 23 to 83 years. The duration of hemodialysis ranged from 2 to 344 months. The bone mineral density of the radius was measured by dual-energy X-ray adsorptiometry, and the ratio of this value to the standard value for the same age and gender was calculated ( Z-score). As an index of atherosclerosis, the intima-media thickness of the carotid artery was measured by high resolution B-mode ultrasonography. Then the relationship between the Z-score and various factors was examined using Spearman's rank correlation analysis and multiple regression analysis. The Z-score showed a negative correlation with the duration of hemodialysis, the carotid intima-media thickness, and the levels of alkaline phosphatase, intact parathyroid hormone, and low-density lipoprotein cholesterol by Spearman's rank correlation analysis. In addition, the Z-score showed a positive correlation with the lipoprotein (a) level and a negative correlation with the duration of hemodialysis, intima-media thickness, intact parathyroid hormone, and low-density lipoprotein cholesterol by multiple regression analysis. These findings suggest that the decrease of bone mineral density in hemodialysis patients is correlated with secondary hyperparathyroidism and hyperlipidemia, which are factors known to promote atherosclerosis, and thus bone density changes might be related to the progression of atherosclerosis, or vice versa.
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PMID:Bone mineral density may be related to atherosclerosis in hemodialysis patients. 1459 55

Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by Pi, parathyroid hormone and by 1,25-dihydroxyvitamin D. Recent studies of inherited and acquired hypophosphatemia [X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and tumor-induced rickets/osteomalacia (TIO)], which exhibit similar biochemical and clinical features, have led to the identification of novel genes, PHEX and FGF23, that play a role in the regulation of Pi homeostasis. The PHEX gene, which is mutated in XLH, encodes an endopeptidase, predominantly expressed in bone and teeth, but not in kidney. FGF-23 may be a substrate of this endopeptidase and may therefore accumulate in patients with XLH. In the case of ADHR mutations in the furin cleavage site, which prevent the processing of FGF-23 into fragments, lead to the accumulation of a "stable" circulating form of the peptide which also inhibits renal Pi reabsorption. In the case of TIO, ectopic overproduction of FGF-23 overwhelms its processing and degradation by PHEX, leading to the accumulation of FGF-23 in the circulation and inhibition of renal Pi reabsorption. Mice homozygous for severely hypomorphic alleles of the Klotho gene exhibit a syndrome resembling human aging, including atherosclerosis, osteoporosis, emphysema, and infertility. The KLOTHO locus is associated with human survival, defined as postnatal life expectancy, and longevity, defined as life expectancy after 75. In considering the relationship of klotho expression to the dietary Pi level, the klotho protein seemed to be negatively controlled by dietary Pi.
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PMID:Inorganic phosphate homeostasis and the role of dietary phosphorus. 1525 67

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis in patients with normal renal function. Plasma homocysteine (Hcy) is increased in patients with chronic renal failure (CRF) and could be linked to their high cardiovascular (CV) morbidity and mortality. We prospectively studied 77 patients (47 males and 30 females aged 62.85 +/- 1.53 yrs) who had been on maintenance hemodialysis (HD) (4 hr/x3/week) for 65.5 +/- 7.23 months. Patients were followed-up for 44 months. At baseline, blood samples were taken for hemoglobin (Hb), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, serum calcium, serum phosphates, parathyroid hormone (PTH), Hcy, vitamin B12, serum and erythrocyte folate and methylentetrahydrofolate-reductase (t-MTH-FR) genotype determination. Plasma Hcy levels of patients were divided into four quartiles. The univariate analysis demonstrated a significant relationship between Hcy and diastolic blood pressure (BP) (r=0.45; p=0.003), and both plasma (r=-0.30; p=0.03) and erythrocyte (r=-0.48; p=0.01) folate levels and CV score (r=0.39; p=0.007). Kaplan-Meier analysis showed that the mortality rate due to CV events was statistically significantly higher in the 4th Hcy quartile (68%; 12 patients) vs. the 3rd quartile (12%; two patients), the 2nd quartile (28%; four patients) and the 1st quartile (14%; two patients) (log-rank test p=0.02). Cox's regression analysis for CV survival showed that Hcy was a positive CV mortality predictor (beta=0.02; hazard ratio=1.031; 95% confidence interval (95% CI): 1.013-1.050; p=0.001), while LDL cholesterol and albumin related negatively to CV mortality (LDL cholesterol: beta=-0.02; hazard ratio=0.095; 95% CI: 0.0957-0.0997; p=0.035; albumin: beta=-2.35; hazard ratio=0.097; 95% CI: 0.011-0.847; p=0.026). Our results show that Hcy is a strong independent mortality predictor in HD patients with a 3% increase in mortality for each 1 micromol/L increase in plasma Hcy concentration. This agrees with previous findings confirming the role of Hcy in predicting CV risk factors in uremic patients.
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PMID:Plasma homocysteine levels and cardiovascular mortality in patients with end-stage renal disease. 1536 61

Patients with end-stage renal disease have markedly increased risk for death from cardiovascular disease. Renal failure is associated with multiple metabolic and endocrinologic abnormalities, and these alterations are involved in advanced atherosclerosis and high cardiovascular risk. Increased insulin resistance index by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance, was an independent predictor of cardiovascular mortality in nondiabetic patients on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading to the atherogenic lipoprotein profile characterized by increased triglyceride-rich remnant lipoproteins such as intermediate-density lipoprotein, an independent factor of increased aortic stiffness. Non-high-density lipoprotein cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other apoB-containing lipoproteins, is an independent factor associated with increased arterial thickness and a predictor of cardiovascular death in hemodialysis patients. The risk for cardiovascular death in hemodialysis patients is associated closely with hypertension and malnutrition, but not with obesity. The constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition in renal failure suggests the presence of another type of metabolic syndrome promoting cardiovascular disease. In addition, vitamin D deficiency and abnormalities in calcium, phosphate, and parathyroid hormone levels increase the death risk from cardiovascular disease in renal failure. It is expected that treatment of these metabolic and endocrinologic alterations would improve the survival of patients with renal failure.
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PMID:Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure: another form of metabolic syndrome. 1549 Apr 3

Etidronate, an analogue of first generation of bisphosphonates, has inhibitory actions on mineralization and hydroxyapatite crystal formation, which is therefore used as a drug to treat ectopic ossification in cases with total hip arthroplasty and spinal cord injury. The effect of bisphosphonates to prevent calcification could be associated with the physical property to attach tightly to hydroxyapatite crystals in bone matrix. A recent investigation suggested that bisphosphonates might prevent arterial calcification through a mechanism associated with the enhanced production of parathyroid hormone-related peptide from vascular smooth muscle cells. A derivative of bisphosphonates to inhibit vascular calcification in atherosclerosis is expected and should be developed in the near future.
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PMID:[Regulation of calcification by bisphosphonates]. 1557 56

Chlamydial infection has been suspected in the pathogenesis of ischemic heart disease. However, it remains undetermined if persistent chlamydial infection is related to cardiovascular mortality in regular hemodialysis (HD) patients. We measured Chlamydia pneumoniae (Cp) antibody seropositivity in 154 HD subjects (age 59 +/- 11 years, time on HD 13 +/- 7 years, male/female = 101/53), and prospectively examined an association between Cp antibody status and cardiovascular death for 56 months of follow-up. Seropositivity for Cp IgA and IgG antibodies at the entry of the study was 50.6 and 60.8%, respectively. There was no significant difference in age, time on HD, serum albumin, C-reactive protein (CRP) and interleukin-6 (IL-6) between those positive and negative for IgA antibodies. During follow-up over 56 months, 31 patients (20.1%) expired, 16 (55.2%) of them of cardiovascular causes. Serological IgA and IgG antibody positivity did not influence mortality, while multiple Cox proportional hazards analysis revealed that diabetes, ischemic changes on electrocardiogram, log-transformed CRP and intact parathyroid hormone were independent determinants of cardiovascular death. These observations suggest that serological Cp antibody status does not affect long-term cardiovascular mortality in chronic HD patients.
Atherosclerosis 2006 Sep
PMID:Association between seroprevalence of anti-chlamydial antibodies and long-term cardiovascular mortality in chronic hemodialysis patients. 1628 59

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