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)

Combined hyperlipidemia predisposes subjects to coronary heart disease. Two lipid abnormalities--increased cholesterol and atherogenic dyslipidemia--are potential targets of lipid-lowering therapy. Successful management of both may require combined drug therapy. Statins are effective low-density lipoprotein (LDL) cholesterol-lowering drugs. For atherogenic dyslipidemia (high triglycerides, small LDL, and low high-density lipoprotein [HDL]), fibrates are potentially beneficial. The present study was designed to examine the safety and efficacy of a combination of low-dose simvastatin and fenofibrate in the treatment of combined hyperlipidemia. It was a randomized, placebo-controlled trial with a crossover design. Three randomized phases were employed (double placebo, simvastatin 10 mg/day and placebo, and simvastatin 10 mg/day plus fenofibrate 200 mg/day). Each phase lasted 3 months, and in the last week of each phase, measurements were made of plasma lipids, lipoprotein cholesterol, plasma apolipoproteins B, C-II, and C-III and LDL speciation on 3 consecutive days. Simvastatin therapy decreased total cholesterol by 27%, non-HDL cholesterol by 30%, total apolipoprotein B by 31%, very low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL) cholesterol by 37%, VLDL + IDL apolipoprotein B by 14%, LDL cholesterol by 28%, and LDL apolipoprotein B by 21%. The addition of fenofibrate caused an additional decrease in VLDL + IDL cholesterol and VLDL + IDL apolipoprotein B by 36% and 32%, respectively. Simvastatin alone caused a small increase in the ratio of large-to-small LDL, whereas the addition of fenofibrate to simvastatin therapy caused a marked increase in the ratio of large-to-small LDL species. Simvastatin alone produced a small (6%) and insignificant increase in HDL cholesterol concentrations. When fenofibrate was added to simvastatin therapy, HDL cholesterol increased significantly by 23%. No significant side effects were observed with either simvastatin alone or with combined drug therapy. Therefore, a combination of simvastatin 10 mg/day and fenofibrate 200 mg/day appears to be effective and safe for the treatment of atherogenic dyslipidemia in combined hyperlipidemia.
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PMID:Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. 1268 35

Combined hyperlipidemia results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins in association with reduced lipoprotein lipase activity. Thus, this condition is typically characterized by concurrent elevations in total cholesterol and triglycerides with decreased high-density lipoprotein cholesterol. High levels of apolipoprotein B-containing lipoproteins, most prominently carried by low-density lipoprotein (LDL) particles, are an important risk factor for coronary heart disease. Statin therapy is highly effective at lowering LDL cholesterol. Despite the benefits of statin treatment for lowering total and LDL cholesterol, many statin-treated patients still have initial or recurrent coronary heart disease events. In this regard, combined therapy with statins and fibrates is more effective in controlling atherogenic dyslipidemia in patients with combined hyperlipidemia than either drug alone. Furthermore, statins and fibrates activate PPARalpha in a synergistic manner providing a molecular rationale for combination treatment in coronary heart disease. Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance so that there may also be additional beneficial metabolic effects of combined statin/fibrates therapy. However, there has been little published evidence that combined therapy is synergistic or even better than monotherapy alone in clinical studies. Therefore, there is a great need to study the effects of combination therapy in patients. When statins are combined with gemfibrozil therapy, this is more likely to be accompanied by myopathy. However, this limitation is not observed when fenofibrate, bezafibrate, or ciprofibrate are used in combination therapy.
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PMID:Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. 1765 32