Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Elevated plasma intermediate density lipoprotein (IDL) is one of the features of uremic dyslipidemia which is potentially atherogenic. We examined the effects of pravastatin, an HMG-CoA reductase inhibitor, on IDL levels as well as other lipoprotein parameters in 19 uremic patients treated with hemodialysis (HD, n = 11) or continuous ambulatory peritoneal dialysis (CAPD, n = 8). The patients were administered 5 mg/day pravastatin for the initial 4 weeks and 10 mg/day for the subsequent 12 weeks. In the analysis of the total subjects, IDL-cholesterol was reduced by 31% as well as low density lipoprotein (LDL)-cholesterol. Cholesterol in very low density lipoprotein (VLDL) also decreased whereas that in high density lipoprotein (HDL) did not. Significant decrease of serum triglycerides was due mainly to reduced IDL- and LDL-triglycerides. Apolipoprotein (apo) A-I did not change, whereas apo A-II, B, C-II, C-III, E, and B/A-I ratio were significantly lowered. Pravastatin did not affect measured activity of lecithin: cholesterol acyltransferase, post-heparin plasma lipoprotein lipase or hepatic triglyceride lipase. HD and CAPD patients responded almost equally to the treatment. IDL elevation was present independent of serum total cholesterol, and it was lowered by pravastatin even in non-hypercholesterolemic subjects. There was no critical adverse effect besides transient and asymptomatic increase of serum creatine kinase level. We conclude that pravastatin can be a safe and effective approach to the management of dyslipidemia in uremic patients who have an elevated level of IDL.
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PMID:Reduction of intermediate density lipoprotein by pravastatin in hemo- and peritoneal dialysis patients. 760 82

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.
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PMID:Currently available hypolipidaemic drugs and future therapeutic developments. 859 27

Hyperlipidemia occurs frequently after heart transplantation, and accelerated coronary artery disease remains the major cause of morbidity and mortality in patients who survive more than 1 year after heart transplantation. However, the risks and benefits of lipid-lowering therapy after heart transplantation remain poorly defined, and national guidelines for lipid-lowering drug therapy do not specifically address treatment of dyslipidemia in transplant recipients. Since the initial reports in the 1980s of rhabdomyolysis in heart transplant patients receiving high-dosage lovastatin, results of 11 post-transplantation series that used lovastatin, simvastatin, or pravastatin at lower dosages as drug monotherapy have been published. These studies have shown an overall 1% incidence of rhabdomyolysis, defined as creatine kinase > 10 times the upper limit of normal plus muscle symptoms. One randomized, controlled prospective trial has investigated the effects of lipid-lowering pharmacotherapy on patient outcome in cardiac transplant recipients. At 1-year follow-up in this nonblinded, single-center trial, patients treated with pravastatin (20 or 40 mg/day) initiated within 2 weeks of transplantation had a significant reduction in mortality rate and a significantly lower incidence of transplant arteriopathy. A number of important issues remain unanswered regarding treatment guidelines in patients with hyperlipidemia after heart transplantation. In January 1995 we began the Heart Transplant Lipid Registry, with 12 participant centers, to gather data prospectively on the efficacy and safety of lipid-lowering drugs in the treatment of dyslipidemia after heart transplantation.
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PMID:Treatment of hyperlipidemia after heart transplantation and rationale for the Heart Transplant Lipid Registry. 880 37

Little is known of the risk factors of recurrent myocardial infarction (MI) among Japanese patients who have survived their first MI. The risk factors for the second MI were studied in 808 of 1,042 consecutive patients who recovered from an acute MI in Iwakuni National Hospital. Multivariate logistic regression analysis revealed that only 3 of 21 variables measured were closely related with the recurrence of MI during a follow-up period of 3.2 +/- 4.3 years: (1) transient atrial fibrillation (relative risk (RR) 3.16), (2) previous cerebrovascular accident (RR 3.05), and (3) dyslipidemia (RR 2.19). Of the parameters of dyslipidemia, a low ratio of high-density lipoprotein-cholesterol (HDL-C) to low-density lipoprotein-cholesterol (LDL-C) alone indicated subsequent MI. None of age, gender, location of the infarction, hypertension, diabetes mellitus, pulmonary congestion (Killip's class > or = 2), peak serum creatine kinase activity, serum total-cholesterol, HDL- and LDL-cholesterol levels, nor smoking habit on admission was a statistically significant predictor for the second MI. The result suggests that more intensive treatment is needed for patients with the 3 risk factors.
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PMID:Risk factors indicating recurrent myocardial infarction after recovery from acute myocardial infarction. 1238 Oct 77

The significant age-adjusted decline in cardiovascular mortality that has occurred over the past three decades is multifactorial. However, the advent of statin therapy has markedly facilitated the optimization of dyslipidemia in patients at risk for coronary events. Statin therapy has proven to be effective in reducing morbidity and mortality in large-scale primary and secondary prevention trials. As with all therapies, the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co A) reductase inhibitors is not without clinical risks. Myopathy, albeit uncommon, was one of the earliest clinical problems associated with statin therapy. Recent data from the large-scale statin mega-trials have clarified the quantitative clinical risk-benefit relationship of reductase inhibitors relative to the induction of muscle toxicity. Histopathologic studies have clarified the potential role of statins in the syndrome of myalgias and normal creatine kinase levels. However, the precise mechanism of statin-associated muscle toxicity remains unclear and is potentially related to genetically mediated muscle enzyme defects, drug interactions, intracellular depletion of metabolic intermediates, and intrinsic properties of the statins per se.
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PMID:Statins and myotoxicity. 1257 93

The safety and tolerability of rosuvastatin were assessed (as of August 2003) using data from 12,400 patients who received 5 to 40 mg of rosuvastatin in a multinational phase II/III program, which represented 12,212 patient-years of continuous exposure to rosuvastatin. An integrated database was used to examine adverse events and laboratory data. In placebo-controlled trials, adverse events, irrespective of causality assessment, occurred in 57.4% of patients who received 5 to 40 mg of rosuvastatin (n = 744) and 56.8% of patients who received placebo (n = 382). In fixed-dose trials with comparator statins, 5 to 40 mg of rosuvastatin showed an adverse event profile similar to those for 10 to 80 mg of atorvastatin, 10 to 80 mg of simvastatin, and 10 to 40 mg of pravastatin. Clinically significant elevations in alanine aminotransferase (>3 times the upper limit of normal) and creatine kinase (>10 times the upper limit of normal) were uncommon (<or=0.2%) in the groups that received rosuvastatin and comparator statins. Myopathy (creatine kinase >10 times the upper limit of normal with muscle symptoms) that was possibly related to treatment occurred in <or=0.03% of patients who took rosuvastatin at doses <or=40 mg. A positive finding of proteinuria with dipstick testing at rosuvastatin doses <or=40 mg was comparable to that seen with other statins, and the development of proteinuria was not predictive of acute or progressive renal disease. No deaths in the program were attributed to rosuvastatin, and no rhabdomyolysis occurred in patients who received 5 to 40 mg of rosuvastatin. Rosuvastatin was well tolerated by a broad range of patients who had dyslipidemia, and its safety profile was similar to those of the comparator statins investigated in this extensive clinical program.
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PMID:Safety of rosuvastatin. 1546 70

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) play a prominent role in the treatment of dyslipidemia. Overall, statins are well tolerated, with a low occurrence of adverse effects. More serious reactions to statins have been reported, although they are rare (e.g., rhabdomyolysis 0.3-13.5 cases/million statin prescriptions). Combination therapy to treat dyslipidemia has become common in many patients; however, it can also increase the risk of serious adverse effects. We report the case of a patient who experienced muscle pain and elevated creatine kinase levels 16 days after the addition of ezetimibe to his atorvastatin therapy for hypercholesterolemia. Twelve days after stopping the ezetimibe, his muscle pain resolved and his serum creatine kinase level returned to baseline. This case report raises questions regarding the safety of high-dose atorvastatin and ezetimibe combination therapy and suggests that caution and careful monitoring may be warranted.
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PMID:Myopathy associated with atorvastatin-ezetimibe combination therapy. 1725 23

Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B; high triglycerides, low high-density lipoprotein (HDL) cholesterol and apoA1; and high lipoprotein(a) (lp[a]). We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacin(ER)) formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels > or = 130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg) and niacin(ER) (500 mg) combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg) and niacin(ER) (1000 mg). An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10%) were lost to follow-up and 4 (3%) withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL) at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 +/- 27, 206.3 +/- 27, 189.8 +/- 31, and 174.9 +/- 27 mg/dL; LDL cholesterol 153.4 +/- 22, 127.3 +/- 21, 109.2 +/- 27, and 95.1 +/- 23 mg/dL; triglycerides 171.1 +/- 72, 159.5 +/- 75, 149.2 +/- 45, and 135.2 +/- 40 mg/dL; HDL cholesterol 45.6 +/- 7, 48.9 +/- 7, 51.6 +/- 9, and 53.9 +/- 10 mg/dL; lp(a) 48.5 +/- 26, 40.1 +/- 21, 35.4 +/- 21, and 26.9 +/- 19 mg/dL; and apoA1/apoB ratio 0.96 +/- 0.7, 1.04 +/- 0.4, 1.17 +/- 0.5, and 1.45 +/- 0.5 (p < 0.01). The percentage of decline in various lipids at 4, 12, and 24 weeks was: total cholesterol 11.8%, 18.8%, and 25.2%; LDL cholesterol 17.0%, 28.8%, and 38.0%; triglyceride 6.8%, 12.8%, and 21.0%; lp(a) 17.5%, 26.9%, and 44.5% respectively (p < 0.01). HDL cholesterol and apoA1/apoB increased by 7.2%, 13.1%, and 18.2%; and 7.9%, 21.9%, and 51.6% respectively (p < 0.01). Target LDL levels (< 100 mg/dL in subjects with manifest coronary heart disease or diabetes; < 130 mg/dL in subjects with > 2 risk factors) were achieved in 92 (80.7%) patients. No significant changes were observed in systolic or diastolic blood pressure, blood creatinine, transaminases, or creatine kinase. A fixed dose combination of lovastatin and niacin(ER) significantly improved cholesterol lipoprotein lipids as well as lp(a) and apoA1/apoB levels in Asian Indian dyslipidemic patients. Satisfactory safety and tolerability profile in this population was also demonstrated.
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PMID:Evaluation of efficacy and safety of fixed dose lovastatin and niacin(ER) combination in asian Indian dyslipidemic patients: a multicentric study. 1731 73

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme paucity of adipose tissue from birth, and early onset of metabolic complications related to insulin resistance. Mutations in three genes, 1-acylglycerol 3-phosphate-O-acyltransferase 2 (AGPAT2), Berardinelli Seip Congenital Lipodystrophy 2 (BSCL2), and Caveolin-1 (CAV1) are associated with the three subtypes of this disorder, CGL1, CGL2 and CGL3, respectively. We report two siblings of Hispanic origin who displayed characteristic features of CGL such as generalized loss of subcutaneous fat from birth, acanthosis nigricans, acromegaloid habitus, umbilical prominence, hepatosplenomegaly, hypoleptinemia, dyslipidemia, and insulin resistance. However, no disease causing variants were detected in the DNA sequence of AGPAT2, BSCL2 or CAV1 genes. Further, whole body magnetic resonance imaging (MRI) in the two siblings revealed marked loss of subcutaneous, intraabdominal and intrathoracic fat like in other patients with CGL, but preservation of bone marrow fat which is invariably lost in all patients with CGL1 and CGL2, but not in the patient reported with CGL3. They also had generalized muscle weakness during infancy and early childhood associated with a nearly fivefold increase in serum creatine kinase (CK) levels, but with normal muscle biopsy and electrophysiologic studies. Both patients were also found to have atlantoaxial dislocation requiring surgical intervention. Thus, this pedigree represents a novel subtype of CGL characterized by generalized loss of body fat but with preservation of bone marrow fat, congenital muscular weakness and cervical spine instability. The genetic basis of this novel subtype remains to be determined.
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PMID:Novel subtype of congenital generalized lipodystrophy associated with muscular weakness and cervical spine instability. 1869 12

Dyslipidemia is an important complication affecting kidney transplant recipients. Statins, the first-line therapy, are often insufficient. Ezetimibe may be effective in combination with statin therapy. We performed a retrospective study to determine the safety and efficacy of ezetimibe treatment in addition to statin therapy among 27 stable renal transplant patients with uncontrolled hypercholesterolemia. We obtained fasting lipid profiles at 3 and 6 months before ezetimibe therapy, while the patients were receiving statins at maximum tolerated doses. Statin doses were stable during the study. All patients received ezetimibe (10 mg) once daily. Fasting lipid profile, kidney function, liver enzymes, creatine kinase, and immunosuppressive drug levels were obtained at baseline as well as at 3 and 6 months post-ezetimibe initiation. Combination therapy resulted in median reductions in total cholesterol of 29% (interquartile range [IQR] 12-39; P = .0001) and 28% (IQR 9-38; P = .0001); in low-density lipoprotein cholesterol of 34% (IQR 16-61; P = .0001) and 44% (IQR 24-56; P = .0001); and in triglycerides of 14% (IQR 4-31; P = .01) and 19% (IQR 1-37; P = .006) at 3 and 6 months post-ezetimibe therapy, respectively. There were no significant differences in high-density lipoprotein cholesterol, renal function, proteinuria, creatine kinase, amylase, liver function, body mass index, or drug levels. There were no adverse drug reactions that mandated treatment withdrawal. When combined with statin therapy ezetimibe seemed to be a safe and effective treatment for uncontrolled dyslipidemia among renal transplant patients.
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PMID:Ezetimibe in the treatment of uncontrolled hyperlipidemia in kidney transplant patients. 1910 Apr 21


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