Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesteryl ester transfer protein (CETP) mediates neutral lipid transport in plasma, resulting in a net transfer of cholesteryl ester from high density lipoprotein to very low density lipoprotein. CETP gene expression is regulated by cholesterol, and plasma CETP level increases in patients with hyperlipidemia and with cholesterol feeding. Simvastatin, unlike cholestyramine, reduces hydroxymethylglutaryl coenzyme A reductase activity and may decrease a cellular pool of cholesterol, which is regulatory for CETP gene expression. The effects of simvastatin and cholestyramine on plasma lipids and CETP in 24 male and 19 female patients with primary hypercholesterolemia were compared. Following a four-week placebo period, patients were randomly assigned to receive either simvastatin or cholestyramine. Medication was increased in a stepwise fashion (from 10 to 40 mg for simvastatin and from 8 to 24 g for cholestyramine) as required at six-week intervals to maintain a low density lipoprotein cholesterol (LDL-C) level below 3.4 mmol/L. At the end of the 18-week study, the mean dose of simvastatin was 28.6 mg/day and of cholestyramine 19.3 g/day. Simvastatin was more effective than cholestyramine in lowering LDL-C (-36.8% versus -27. 2%; P=0.031) and triglycerides (-8.5% versus +12.5%; P=0.045). Plasma CETP level decreased by 14.8% following treatment with simvastatin (P=0.003) but did not change following cholestyramine treatment. This study demonstrates that, compared with cholestyramine, simvastatin results in more favourable improvements in the plasma lipoprotein profile and also lowers plasma levels of CETP.
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PMID:Comparative effects of simvastatin and cholestyramine on plasma lipoproteins and CETP in humans. 1051 34

Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is widely used to treat hyperlipidaemia. Although myalgias are recognized adverse effects, clinically significant elevations in serum creatine phosphokinase (CPK) levels are uncommon. We describe a case of rhabdomyolysis and acute renal failure associated with concomitant use of simvastatin and warfarin. Rhabdomyolysis and renal failure occurred 7 days after warfarin (5 mg day-1) was added to a chronic stable dose of simvastatin (20 mg day-1) and resolved abruptly after discontinuation of simvastatin. We recommend careful monitoring when warfarin is given to patients receiving simvastatin.
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PMID:Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. 1062 Jan 5

Sand rats develop obesity, insulin-resistance, hyperlipidemia and prediabetes, when given a standard laboratory chow diet. We have used this model to demonstrate the beneficial action of olea europea var. oleaster leaves to regulate unbalanced metabolism. 32 sand rats fed on hypercaloric diet during 7 months, were divided into 3 groups: controls (n=10), treated by plant (n=13) and treated by simvastatin (Zoco); hypocholesterolemic drug. The plant decoction prepared at 10% was given orally at the rate of 1.5 ml/100g during 3 months. Results show that the plant presents a hypocholesterolemic effect (42%) related to decreases in LDL and VLDL cholesterol. In addition, hypoglycemic (16%) and antihyperglycemic (40%) effects were observed accompanied by a 27% decrease in insulin. Chronic treatment with Zocor reduced total cholesterol (32%), LDL and VLDL cholesterol. Both of treatments produced no significantly reduction in plasma levels of triglycerides and HDL cholesterol. No noxions effect of this plant have been observed in usual doses.
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PMID:[Therapeutic effect of Olea europea var. oleaster leaves on carbohydrate and lipid metabolism in obese and prediabetic sand rats (Psammomys obesus)]. 1091 76

Mixed hyperlipidemia is characterized by both elevated total cholesterol and triglycerides. It is estimated to account for 10% to 20% of patients with dyslipidemia. This study assessed the lipid-altering efficacy and tolerability of simvastatin 40 and 80 mg/day as monotherapy. One hundred thirty patients (62 women [48%], 24 [16%] with type 2 diabetes mellitus, mean age 53 years) with mixed hyperlipidemia (baseline low-density lipoprotein [LDL] cholesterol 156 mg/dl [mean], and triglycerides 391 mg/dl [median) were randomized in a multicenter, double-masked, placebo-controlled, 3-period, 22-week, balanced crossover study, and received placebo, and simvastatin 40 and 80 mg/day each for 6 weeks. Compared with placebo, simvastatin produced significant (p <0.01) and dose-dependent changes in all lipid and lipoprotein parameters (LDL cholesterol 2.1%, -28.9%, and -35.5%; triglycerides -3.5%, -27.8%, and -33.0%; high-density lipoprotein cholesterol 3.3%, 13.1%, and 15. 7%; apolipoprotein B 3.8%, -23.1%, and -30.6%; and apolipoprotein A-I 4.0%, 8.2%, and 10.5% with placebo, and simvastatin 40 and 80 mg/day, respectively). The changes were consistent in patients with diabetes mellitus. One patient taking simvastatin 80 mg/day had an asymptomatic and reversible increase in hepatic transaminases 3 times above the upper limit of normal. Simvastatin 40 and 80 mg/day is effective in patients with mixed hyperlipidemia across the entire lipid and lipoprotein profile. The reductions in LDL cholesterol and triglycerides are large, significant, and dose dependent. The increase in high-density lipoprotein cholesterol was greater than that observed in patients with hypercholesterolemia, and appears dose dependent.
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PMID:Effects of simvastatin (40 and 80 mg/day) in patients with mixed hyperlipidemia. 1094 33

Recent studies have shown that statins are effective in reducing fasting low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels. However, it remains unknown if treatment with statins also lowers daily postprandial triglyceride concentrations, which may promote atherogenesis in type 2 diabetes subjects. Forty-one subjects with type 2 diabetes and combined hyperlipidemia who had stable glycemic control were randomly assigned to take simvastatin 20 mg (n = 27) or a placebo (n = 14) once daily for 12 weeks. The medication dosage was doubled after 4 weeks if a subject's LDL-C was not less than 130 mg/dL. Among these participants, 24 subjects (15 on simvastatin and 9 on placebo) agreed to take a meal tolerance test with isocaloric mixed meals (carbohydrate, 52%; fat, 33%, and protein, 15% of the daily caloric intake) and daytime hourly blood sampling from 8 AM to 4 PM. Simvastatin treatment reduced the fasting total cholesterol level from 237 +/- 5 to 178 +/- 6 mg/dL (-25%), the LDL cholesterol level from 150 +/- 6 to 87 +/- 5 mg/dL (-40%), and raised high-density lipoprotein-cholesterol (HDL-C) level from 36 +/- 2 to 40 +/- 2 mg/dL (+11%) (all P <.001). Fasting and daily ambient triglyceride concentrations from 8 AM to 4 PM decreased significantly in response to simvastatin administration (P <.001), but not to the placebo (P =.305). Simvastatin treatment not only decreased total cholesterol and LDL-C levels and increased HDL-C levels effectively, it also decreased fasting, as well as daily postprandial triglyceride concentrations, but had no effect on glycemic control in type 2 diabetes subjects with combined hyperlipidemia.
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PMID:Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia. 1123 Jul 91

Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.
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PMID:Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes. 1135 79

Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were compared in-patients undergoing renal transplantation. The study included 32 cases of renal transplantation recipients who randomized to the CsA treatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism. The serum lipid levels in both groups were significantly increased at 1 month after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions. In study 2, 1 month after renal transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition, there were significant decreases in very-low-density lipoprotein cholesterol (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin levels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects.
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PMID:Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus. 1158 21

The relationships between direct-to-consumer advertising expenditures and the monthly frequencies of diagnoses and prescriptions written associated with the products advertised are examined. The analyses utilized quasi-experimental time-series techniques. Data from the National Ambulatory Medical Care Survey and Competitive Media Reporting were used to calculate monthly levels of the dependent and independent variables. The dependent variables included monthly frequencies of diagnoses for the products' FDA-approved indications, medications prescribed within the advertised pharmaceutical class, and medications prescribed for the specific advertised agent. The independent variables included monthly expenditures for advertising each pharmaceutical class and each specific agent. Several significant monthly relationships were found. The diagnoses of hyperlipidemia (p = 0.008) and the number of prescriptions written for antilipemics (p = 0.003) were positively associated with the advertising expenditure for antilipemics. The number of prescriptions written for Claritin (p = 0.004) and Zocor (p < 0.001) was positively related to the advertising expenditure for their respective pharmaceutical classes; the amount of prescriptions written for Hismanal (p = 0.007), Seldane (p < 0.001), and Zantac (p = 0.004) was negatively related to the advertising expenditure for their respective pharmaceutical classes. The number of prescriptions written for Claritin (p = 0.005) and Zocor (p < 0.001) was positively related to the advertising expenditure for each specific product; the amount of prescriptions written for Hismanal (p = 0.049) was negatively associated with the amount of money spent specifically advertising the agent. No significant associations were found in antihypertensive drugs and drugs to treat benign prostatic hypertrophy. The results of the analyses suggest that the direct-to-consumer advertising expenditure is associated with physician diagnosing and physician prescribing for certain drugs and drug classes.
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PMID:Relationship between direct-to-consumer advertising and physician diagnosing and prescribing. 1181 66

Congenital analbuminaemia, a rare disorder associated with defective albumin synthesis, is characterised by hyperlipidaemia. Administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGRI) to analbuminaemic rats have demonstrated no significant effect on plasma lipids, however no published information regarding HMGRI treatment could be found in human subjects. The efficacy, safety and tolerability of Simvastatin was thus investigated in 2 South African patients with analbuminaemia, a 21 year old Caucasian male (H-B) and a 61 year old black male (A-K). In the case of A-K, the lipid profile responded predictably but H-B responded less that expected from general experience with Simvastatin. Both subjects, however, experienced a three- to five-fold increase in creatine kinase. The use of HMGRI's should thus be used cautiously in these patients and it may be advisable to reserve treatment for secondary prevention.
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PMID:The use of simvastatin in analbuminaemia. 1191 66

Low density lipoprotein receptor deficient (LDLR-KO) and apolipoprotein E deficient (apo E-KO) mice both develop hyperlipidemia and atherosclerosis by different mechanisms. The aim of the present study was to compare the effects of simvastatin on cholesterol levels, endothelial dysfunction, and aortic lesions in these two models of experimental atherosclerosis. Male LDLR-KO mice fed a high cholesterol (HC; 1%) diet developed atherosclerosis at 8 months of age with hypercholesterolemia. The addition of simvastatin (300 mg/kg daily) to the HC diet for 2 more months lowered total cholesterol levels by approximately 57% and reduced aortic plaque area by approximately 15% compared with the LDLR-KO mice continued on HC diet alone, P<0.05. Simvastatin treatment also improved acetylcholine (ACh)-induced endothelium-dependent vasorelaxation in isolated aortic rings, which was associated with an increase in NOS-3 expression by approximately 88% in the aorta measured by real time polymerase chain reaction (PCR), P<0.05. In contrast, in age-matched male apo E-KO mice fed a normal diet, the same treatment of simvastatin elevated serum total cholesterol by approximately 35%, increased aortic plaque area by approximately 15%, and had no effect on endothelial function. These results suggest that the therapeutic effects of simvastatin may depend on the presence of a functional apolipoprotein E.
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PMID:Anti-atherosclerotic effect of simvastatin depends on the presence of apolipoprotein E. 1194 94


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