Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current medical practice recommends the use of alternatives to estrogen-replacement therapy for the treatment of menopausal sequelae in younger women with breast cancer, although this clinical recommendation is undergoing reappraisal. Until prospective randomized studies addressing hormone use in this population are available, estrogen use in breast cancer patients will remain controversial. Because estrogen-replacement therapy is not the standard of practice and there is limited information available on nonestrogen therapies, women with breast cancer who are menopausal may not be prescribed or counseled about nonestrogen options. The efficacy, safety, and extent of use of most nonestrogen treatment modalities (other hormonal preparations, nonhormonal drugs, homeopathic preparations, and non-drug treatments) are not well documented and, unlike estrogen, many are selective in their benefit and do not share estrogen's universal impact. The use of several nonestrogen approaches for the prevention and treatment of osteoporosis has been promising. Traditional recommendations to maintain skeletal integrity, such as weight-bearing exercise; a diet rich in calcium and limited in caffeine, alcohol, and protein; avoidance of smoking; and measures to minimize trauma have been expanded to include the use or investigation of drugs (either alone or in combination). These drugs include progestins, vitamin D metabolites, injectable and intranasal synthetic salmon calcitonin, bisphosphonates, sodium fluoride, parathyroid hormone, growth factors, tamoxifen, etc. Strict control of the known risk factors, such as smoking, dyslipidemia, and hypertension as well as exercise, weight control, and the use of tamoxifen, are employed for the prevention and treatment of cardiovascular complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonhormonal alternatives for the management of early menopause in younger women with breast cancer. 799 60

Cardiovascular complications account for more than 50% of death in hemodialysis patients. Strong and independent predictors of mortality or cardiovascular complications are low levels of serum albumin, high plasma C-reactive protein and lipoprotein(a), plasma proteins that are described to function as negative or positive acute phase reactants. Further prominent and known risk factors that contribute to the increased incidence of atherosclerosis in hemodialysis patients are disorders in lipoprotein metabolism and elevated plasma fibrinogen concentrations. The latter has also been described to increase following acute or chronic inflammation. The main metabolic abnormality of the lipoprotein profile is a delayed catabolism of triglyceride-rich apoB-containing lipoproteins caused by a decreased activity of lipolytic enzymes. Inhibition of lipoprotein lipase activity by cytokines or parathyroid hormone impedes conversion of very-low-density lipoprotein to low-density lipoprotein, resulting in remnant accumulation and hypertriglyceridemia. Another acute phase condition, namely, acute myocardial infarction, results in a similar pattern of dyslipidemia and coagulation disorder. In summary, the acute phase response deeply influences serum lipids and lipoproteins as well as other atherogenic acute phase proteins in hemodialysis patients. Appreciation of acute phase lipoprotein changes is essential for accurate diagnosis of dyslipidemias, proper design of future clinical studies, and correct interpretation of published data.
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PMID:Inflammation, dyslipidemia and vascular risk factors in hemodialysis patients. 935 Jun 81

To determine the influence of parathyroid hormone (PTH) on lipid disturbances of uremia, the lipid profile was determined in 34 hemodialysis (HD) patients, comparing lipid parameters among subjects classified according to their intact PTH level. Furthermore, the effect of correction of severe secondary hyperparathyroidism on serum lipids was evaluated in 7 patients after parathyroidectomy. Total cholesterol, high-density lipoproteins (HDL), triglycerides, apolipoproteins A-I and B-100 (Apo B and Apo B), lipoprotein(a) and the ratios of cholesterol/HDL and Apo A/Apo B were analyzed. There was no correlation between serum lipids and PTH levels in the total group. Lipid profile was similar among patients classified according to their PTH level. No correlations were observed in either group between lipids and PTH. Lipid profile did not change in the seven patients with severe secondary hyperparathyroidism after parathyroidectomy. In conclusion, there was no relationship between PTH and lipids and risk ratios in HD patients. Lipid profile did not change in patients with severe secondary hyperparathyroidism after parathyroidectomy. These findings suggest that PTH does not play a significant role in the dyslipidemia of renal failure.
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PMID:Relationship between serum parathyroid hormone levels and lipid profile in hemodialysis patients. Evolution of lipid parameters after parathyroidectomy. 961 94

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

To determine whether an "atherogenic" diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an interaction between calcium phosphate and phospholipids at the kidney level. The biological significance of these findings for the etiology of idiopathic calcium urolithiasis in humans is uncertain, but the presented animal model may be helpful when designing clinical studies.
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PMID:Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction. 1122 20

Studies in the uremic rat indicate that insulin resistance and glucose intolerance leading to dyslipidemia are associated with a hyperparathyroid-induced increase in cytosolic calcium ([Ca++i]). These alterations are reversed with verapamil, but recur after discontinuation of the drug, suggesting that increased [Ca++i] is responsible for the metabolic derangement. To our knowledge, no similar studies have been conducted in humans. We retrospectively examined, over 12-year period, the effects of factors that lower [Ca++i] on total serum cholesterol and triglycerides in 176 peritoneal dialysis (PD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on the morbidity and mortality outcome related to atherosclerotic vascular disease. Diabetic patients were excluded from the study, because their dyslipidemia and vascular disease are mediated via a different mechanism. The patients were classified into four groups. Group I [high parathyroid hormone (PTH) in the absence of calcium channel blockers (CCBs), n = 56] represented the highest [Ca++i]. Group II (high PTH in the presence of CCBs, n = 43) and group III (lower PTH in the absence of CCBs, n = 37) represented intermediate [Ca++i]. Group IV (lower PTH in the presence of CCBs, n = 40) represented the lowest [Ca++i]. High PTH was defined as > or = 3.0 times normal; lower PTH, as < 3.0 times normal. Lower [Ca++i] was achieved through the use of CCBs, or through lower PTH, or both. Lower PTH was achieved by parathyroidectomy or calcitriol administration. The four groups showed no differences in age, sex, race, weight, dialysis duration, or primary disease. Group I showed a mean serum cholesterol of 358 +/- 27 mg/dL and serum triglycerides of 469 +/- 41 mg/dL. Group II showed mean serum cholesterol of 198 +/- 21 mg/dL and serum triglycerides of 147 +/- 17 mg/dL. Group III showed a mean serum cholesterol of 205 +/- 20 mg/dL and serum triglycerides of 174 +/- 16 mg/dL. Group IV showed mean serum cholesterol of 184 +/- 10 mg/dL (p = 0.008) and serum triglycerides of 103 +/- 8 mg/dL (p = 0.005). The cardiovascular morbidity and mortality incidences were: group I, 64%; group II, 27%; group III, 31%; and group IV, 20% (p = 0.002). We conclude that, in non diabetic PD patients, dyslipidemia is related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++i]. Lowering [Ca++i] by decreasing the parathormone level (via parathyroidectomy or calcitriol administration), or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long-term morbidity and mortality related to atherosclerotic vascular disease.
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PMID:Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular morbidity and mortality in peritoneal dialysis patients. 1151 Feb 92

In renal failure, parathyroid hormone (PTH) is not only involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa; it is also a permissive factor in the genesis of hypertension, cardiovascular damage, and dyslipidemia. The allosteric activator of the calcium sensing receptor NPSR-568 (R-568) has been shown to reduce the serum intact PTH (iPTH) concentration in uremic rats. It was the purpose of this study in subtotally nephrectomized (SNX) rats to compare pharmacologic abrogation of secondary hyperparathyroidism by R-568 with parathyroidectomy (PTX). The effects on progression of renal failure, BP, and lipid and structural parameters of kidney and heart were studied. Four groups of male SD-rats were studied: (1) sham-operated + vehicle-treated rats (controls); (2) SNX + vehicle-treated rats (SNX); (3) parathyroidectomized SNX + vehicle-treated rats (SNX+PTX); and (4) SNX + calcimimetic R-568-treated rats (SNX+R-568). R-568 (50 micro mol/kg per d) was administered by gavage. Eight weeks after SNX, serum creatinine concentration, urinary albumin excretion, BP, and serum LDL-cholesterol concentration were significantly lower in both R-568-treated and parathyroidectomized SNX compared with vehicle-treated SNX. In addition, structural abnormalities of the kidney (glomerulosclerosis, tubulointerstitial changes) and the heart (interstitial fibrosis, capillary length density, arteriolar wall thickness) were significantly less pronounced than in vehicle-treated SNX. It is concluded that in experimental renal failure abrogation of hyperparathyroidism by administration of a calcimimetic or PTX similarly attenuates progression of renal failure. Furthermore, it interferes with the development of cardiovascular risk factors and cardiac remodeling.
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PMID:Beneficial effects of calcimimetics on progression of renal failure and cardiovascular risk factors. 1266 Mar 30

Cardiovascular calcification is a common consequence of diabetes. High fat diets induce diabetes and arterial calcification in male low density lipoprotein receptor (LDLR) -/- mice; calcification occurs via Msx2 signaling that promotes the osteogenic differentiation of arterial myofibroblasts. We studied regulation of arterial osteogenesis by human parathyroid hormone (PTH) (1-34) (also called teriparatide) in LDLR -/- mice fed diabetogenic diets for 4 weeks. LDLR -/- mice were treated with vehicle or 0.4 mg/kg of PTH(1-34) subcutaneously five times/week. Gene expression was determined from single aortas and hind limb RNA by fluorescence reverse transcription-PCR. Valve calcification was determined by histological staining of cardiac sections using image analysis to quantify valve leaflet mineralization. PTH(1-34) increased bone mineral content (by dual energy x-ray absorptiometry) in LDLR -/- mice, with induction of osseous osteopontin (OPN) expression and serum OPN levels (>150 nM); PTH(1-34) did not significantly change serum glucose, lipids, body weight, or fat mass. PTH(1-34) suppressed aortic OPN and Msx2 expression >50% and decreased cardiac valve calcification 80% (8.3 +/- 1.5% versus 1.4 +/- 0.5%; p < 0.001). Of the known circulating regulators of vascular calcification (OPN, osteoprotegerin, and leptin), PTH(1-34) regulated only serum OPN. We therefore studied actions of PTH(1-34) and OPN in vitro on cells induced to mineralize with Msx2. OPN (5-50 nM) reversed Msx2-induced mineralization. PTH(1-34) inhibited mineralization by 40% and down-regulated Msx2 in aortic myofibroblasts. PTH(1-34) inhibits vascular calcification and aortic osteogenic differentiation via direct actions and potentially via circulating OPN. PTH(1-34) exerts beneficial actions at early stages of macrovascular disease responses to diabetes and dyslipidemia.
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PMID:Teriparatide (human parathyroid hormone (1-34)) inhibits osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice. 1450 75

The reduction of cardiovascular disease risk in kidney failure involves treatment of modifiable risk factors and provision of proven interventions to patients with established disease. Volume status management is key to blood pressure control. Statins are the agents of choice for the treatment of dyslipidemia. Target hemoglobin levels should be achieved using intravenous iron and erythropoietic agents. Combinations of calcium and noncalcium-containing phosphorus binders and vitamin D and its analogues should be used to attain target parathyroid hormone, phosphorus, and calcium phosphorus product levels. beta Blockers and aspirin are recommended in patients with ischemic heart disease and angiotensin-converting enzyme inhibitors (or angiotensin II receptor blockers), and beta blockers are recommended in patients with heart failure with reduced ejection fraction. In patients who require revascularization, studies suggest a survival benefit of coronary artery bypass graft surgery over percutaneous transluminal coronary angioplasty and coronary artery stenting.
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PMID:Treating the Patient with Kidney Failure to Reduce Cardiovascular Disease Risk. 1521 21

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


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