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)

The results of recently published studies on primary and secondary prevention of coronary heart disease with HMG-CoA reductase inhibitors--statins--support their use in patients with primary hypercholesterolaemia or mixed hyperlipidaemia, with or without atherosclerotic vascular disease. From a pharmacological point of view, statins inhibit HMG-CoA reductase, reduce the endogenous synthesis of cholesterol and increase the apoB/apoE lipoprotein clearance from plasma. Recent studies confirm that HMG-CoA reductase inhibitors may also decrease hepatic production of VLDL and LDL-cholesterol. However, they have different pharmacokinetic properties and variable effectiveness with potential clinical implications. These drugs are generally well tolerated with a similar profile of adverse effects (gastrointestinal effects, hepatic dysfunction and myopathy). The knowledge of their pharmacodynamic and pharmacokinetic properties can lead to a rational use and greater understanding of their potential benefits.
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PMID:[HMG-CoA reductase inhibitors: a brief review of their pharmacological properties and clinical efficacy in cardiovascular disease]. 1009 28

Although myopathy is considered an adverse effect of treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates in combined hyperlipidemia, the present study was performed to investigate whether combined hyperlipidemia itself is associated with skeletal muscle pathology and whether lipid-lowering intervention has beneficial effects. To investigate whether combined hyperlipidemia is associated with skeletal muscle pathology, 10 male patients and 15 normolipidemic controls underwent a 45-minute standardized bicycle ergometer test at a load of 2 W/kg lean body mass (parallel study). One- and 8-hour postexercise increments in the plasma level of the muscle proteins creatine kinase (CK), myoglobin (Mb), and fatty acid-binding protein (FABP) were assessed as parameters for (subclinical) skeletal muscle pathology. The 8-hour postexercise increments in CK and Mb and 1-hour postexercise increment in Mb were significantly higher in patients than in controls, thus indicating increased exercise-induced muscle membrane permeability in combined hyperlipidemia. To investigate the effects of lipid-lowering intervention on skeletal muscle in combined hyperlipidemia, 21 subjects with combined hyperlipidemia were randomized double-blindly to receive 6 weeks of treatment with fluvastatin 40 mg/d, gemfibrozil 600 mg twice daily, or combination therapy. All subjects underwent an ergometer test before and after treatment. Gemfibrozil treatment alone reduced the CK increments 8 hours postexercise by 47% and the FABP increments 1 and 8 hours postexercise by 83% and 101%, respectively (all P < .05). Combined treatment reduced Mb increments 1 hour postexercise by 54% and FABP increments 8 hours postexercise by 44% (all P < .05). A highly significant correlation existed between therapy-induced changes in plasma triglycerides and changes in postexercise increments of FABP and Mb. In conclusion, combined hyperlipidemia is associated with an increased exercise-induced release of muscle proteins, which is ameliorated by triglyceride-lowering intervention. As FABP is an indicator for ischemia-induced skeletal muscle pathology, a possible explanation is the impaired muscle blood flow during hypertriglyceridemia, which may be reversed by triglyceride-lowering intervention. The mechanism and clinical relevance of these findings remain to be investigated.
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PMID:Combined hyperlipidemia is associated with increased exercise-induced muscle protein release which is improved by triglyceride-lowering intervention. 1059 82

BACKGROUND: Pravastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It prevents mevalonate synthesis, reducing endogenous cholesterol production, and reduces cholesterol content in the liver, thus resulting in a down-regulation of low-density lipoprotein receptor production. Gemfibrozil reduces very low-density lipoprotein production and low-density lipoprotein-cholesterol level and increases very low-density lipoprotein catabolism. Therefore, it was suggested that combination therapy with both drugs could effect greater reduction of cholesterol levels as compared to pravastatin alone. The present study was carried out to evaluate the efficacy and safety of pravastatin as a monotherapy or in combination with gemfibrozil in the treatment of patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia. METHODS AND RESULTS: Forty-one patients were included in the study. All patients initially followed 6 weeks of hypolipidemic diet; subsequently they were randomized and received either 20 mg once daily of pravastatin alone (n = 13) or 20 mg of pravastatin together with 600 mg of gemfibrozil twice daily (n = 14). As a control, 14 patients were treated with diet only. The treatment lasted 24 months and clinical evaluation and laboratory tests were done at given time points. Both groups of treated patients showed an early reduction (3 months) of total (about 30% P <.01 vs controls), low-density lipoprotein (about 35%, P <.01 vs controls) and very low-density lipoprotein cholesterol levels (about 18%, P = NS). In contrast, high-density lipoprotein cholesterol levels increased significantly in patients treated with pravastatin and gemfibrozil (about 20%, P <.05 vs controls). Pravastatin treatment alone reduced the level of serum triglycerides as efficiently as in combination with gemfibrozil. Data showed a sustained normalization of lipid profile until 24 months. However, this effect was achieved in patients that had rather low levels of triglycerides. During the treatment we did not observe any difference in the incidence of possible drug-related side effects. Severe myopathy or rhabdomyolysis was not observed at the doses of the drugs used in our study. CONCLUSIONS: Therapy with pravastatin and in combination with gemfibrozil resulted in significant and sustained normalization of lipid profile in high-risk patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia.
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PMID:Long-term Treatment With Pravastatin Alone and in Combination With Gemfibrozil in Familial Type IIB Hyperlipoproteinemia or Combined Hyperlipidemia. 1068 38

HMG-CoA reductase inhibitors (lovastatin, simvastatin, fluvastatin, pravastatin) constitute a potent class of cholesterol-lowering agents, which are increasingly being used these days for primary and secondary prevention of atherosclerotic heart disease. Despite having good overall safety and efficacy profiles, these medications can still cause significant adverse effects including transient elevation of hepatic transaminases, myopathy, and rhabdomyolysis. Preclinical studies have demonstrated a potential of neoplasia in rats. However in clinical trials HMG-CoA reductase inhibitors have not been found to be neoplastic in humans. The dosage used in humans is also significantly lower and therefore it is expected to have a good safety margin. But this may not be entirely true considering the mechanism of neoplastic transformation, which is thought to be different in humans as compared to other species. We report a patient, who developed follicular adenoma with prominent Hurthle cell changes after being on simvastatin for three months but not during one year of pravastatin therapy. In elderly female patients with hyperlipidemia requiring pharmacologic treatment, especially those with a prior history of multinodular goiter, one should consider using an agent which has not been shown to cause thyroid tumors even in animal models. Patients should continue to be followed with frequent periodic thyroid palpation in addition to the usual biochemical monitoring required while on these agents.
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PMID:Development of thyroid follicular adenoma on simvastatin therapy. 1084 48

Combination therapy for hyperlipidemia, especially combined hyperlipidemia, may have advantages over single drug therapy, affording better improvement in lipoprotein risk factors and possibly better prevention of atherothrombotic events. Although preliminary experience has been gained using treatment combinations of niacin with statins, and fibrates with statins, few studies have focused on angiographic or clinical outcomes. Both of these treatment combinations increase the risk of drug-induced myopathy and rhabdomyolysis. Current estimates of myopathy incidence are much lower than original estimates, but the relative safety of combined therapy might depend upon employing low or moderate statin doses. Safety depends critically upon educating the patient to respond appropriately to muscle symptoms, to intercurrent illness, and to concurrent use of certain other medications. Other useful drug combinations include those derived by addition of fish oil, bile acid binding resins, or stanol esters, as well as nonstatin combinations such as niacin-resin or fibrate-niacin.
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PMID:Combination drug therapy for combined hyperlipidemia. 1098 Aug 49

The long-term efficacy and safety of fluvastatin monotherapy was compared with that of the combination of fluvastatin and fenofibrate in 104 patients with coronary heart disease and combined hyperlipidemia in an open, randomised, parallel group, clinical study of 78 weeks duration. Combined hyperlipidemia was defined as LDL-cholesterol 4.1 mmol/l and higher and triglycerides between 2.5 and 4.5 mmol/l after 8 weeks of dietary intervention. The patients were treated with either fluvastatin 40 mg daily or with the combination of fluvastatin (20 mg daily) and micronized fenofibrate 200 mg daily. Mean values of total and LDL-cholesterol decreased by 19.3% and 29.7% respectively after fluvastatin treatment and by 21.5% and 29.1% respectively after the combination of fluvastatin and fenofibrate treatment. The differences between the treated groups were not significant. Mean values of HDL-cholesterol increased significantly more after the combination of fluvastatin and fenofibrate than after fluvastatin monotherapy (26% vs. 9.9%). The mean values of triglycerides decreased significantly more after the combination treatment than after fluvastatin monotherapy (-40.2% vs. -19.7%). The treatment in both groups was well tolerated and no signs of myopathy were observed in any patient. The study was discontinued in 1 patient due to the increase of liver enzymes. The most frequently observed side effects were minor gastrointestinal symptoms, which were more frequent in patients treated by the combination of fluvastatin and fenofibrate. Thus our results demonstrate that the combination of fluvastatin and fenofibrate is an effective and safe treatment option for patients with coronary heart disease and mild to moderate combined hyperlipidemia if a more radical lowering of triglycerides and increase of HDL-cholesterol is desired.
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PMID:[Long-term treatment of combined hyperlipidemia with a combination of fluvastatin and fenofibrate]. 1104 81

Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.
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PMID:Features of carnitine palmitoyltransferase type I deficiency. 1128 80

Statins are competitive inhibitors of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase and are the most commonly used drugs to treat hyperlipidaemia. Muscle toxicity is an adverse effect reported with a low incidence and rarely associated with acute renal failure due to rhabdomyolysis. We describe two patients with chronic renal failure treated with pravastatin and simvastatin who suffered rhabdomyolysis and acute renal failure. One patient started pravastatin several days after cessation of bezafibrate and developed acute renal failure without needing dialysis. The other was treated with simvastatin three years ago and suffered rhabdomyolysis when renal function was impaired after indomethacin was prescribed for backache. He needed hemodialysis because of acute cardiac failure and died from a respiratory infection while on mechanical ventilation. Myopathy was reversible in both patients. We recommend starting statins with the lower doses in chronic renal failure and monitoring muscle enzymes when renal function changes or when new drugs with potential interactions are prescribed.
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PMID:[Rhabdomyolysis and acute renal failure secondary to statins]. 1198 93

We conducted a population-based cohort study to estimate the risk of myopathy associated with use of lipid-lowering drugs. Using data from general practices in the United Kingdom in 1991 through 1997, we identified three cohorts of individuals 40 to 74 years of age. One cohort comprised 17,219 persons who had received at least one prescription for lipid-lowering drugs in the period; a second cohort consisted of patients with a hyperlipidemia diagnosis who had not been prescribed lipid-lowering drugs (N = 28,974); and a third cohort comprised 50,000 individuals from the general population with no diagnosis of hyperlipidemia. The incidence rate of myopathy in the cohort of users of lipid-lowering drugs was 2.3 per 10,000 person-years [95% confidence interval (95% CI) = 1.2-4.4], which exceeded the incidence rates observed in the nontreated hyperlipidemia cohort [0 per 10,000 person-years (95% CI = 0.0-0.4)] and the general population [0.2 per 10,000 person-years (95% CI = 0.1-0.4)]. The relative risks of myopathy in current users of fibrates and statins compared with nonusers were 42.4 (95% CI = 11.6-170.5) and 7.6 (95% CI = 1.4-41.3), respectively. Potential risk factors other than drug use could not explain our findings in the nested case-control analysis. We conclude that use of lipid-lowering drugs is associated with a substantially greater risk of myopathy, which is most pronounced for fibrates. The absolute risk of myopathy in users of lipid-lowering drugs is, however, small.
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PMID:Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. 1150 77

Since the adoption of highly active antiretroviral therapy (HAART) in the mid-1990s, certain metabolic toxicities have been increasingly recognized. These include a fat redistribution syndrome (lipohypertrophy, lipoatrophy), hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and osteonecrosis). Metabolic complications are principally reported with protease inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with all classes of antiretroviral therapy. In this review, we summarize the epidemiology, pathogenesis and management of these various toxicities.
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PMID:The metabolic toxicities of antiretroviral therapy. 1151 63


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