Drug treatment of combined hyperlipidemia.
Combined hyperlipidemia is increasing in frequency and is the most common lipid disorder associated with obesity, insulin resistance and diabetes mellitus. It is associated with other features of the metabolic syndrome including hypertension, hyperuricemia, hyperinsulinemia and highly atherogenic subfractions of lipoprotein remnant particles including small dense low density lipoprotein-cholesterol. This review examines the mechanisms by which combined hyperlipidemia arises and the various drugs including fibric acid derivatives, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and nicotinic acid which can be used either as monotherapy or in combination to manage it and to improve prognosis from atherosclerotic disease in diabetes mellitus, insulin resistant states and primary combined hyperlipidemia. The therapeutic approach to combined hyperlipidemia involves determination of whether the cause is hepatocyte damage or metabolic derangements. Combined hyperlipidemia due to hepatocyte damage should be treated by attention to the primary cause. In the case of metabolic dysfunction because of imbalance in glucose and fat metabolism, therapy of diabetes mellitus and obesity should be optimised prior to commencement of lipid lowering drugs. Both fibric acid derivatives and HMG-CoA reductase inhibitors can be used in the treatment of combined hyperlipidemia with fibric acid derivatives having greater effects on triglycerides and HMG-CoA reductase inhibitors on LDL-C though both have effects on the other cardiovascular risk factors. There is some evidence of benefit with both interventions in mild combined hyperlipidemias and large scale trials are underway. Fibric acid derivatives and HMG-CoA reductase inhibitor therapy can be combined with care, provided that gemfibrozil is avoided, fibric acid derivatives are given in the mornings and shorter half -life HMG-CoA reductase inhibitors are used at night. Combined hyperlipidemia emergencies occur with predominant hypertriglyceridemia in pregnancy or as a cause of pancreatitis. Therapy in the former should aim to reduce chylomicron production by a low fat diet and intervention to suppress VLDL-C secretion using omega-3 fatty acids. In the latter case, fluid therapy alone and medium chain plasma triglyceride infusions usually reduce levels satisfactorily though apheresis may be required. Blood glucose levels also need aggressive management in these conditions. Combined hyperlipidemia is likely to become an increasing problem with the increase in the prevalence of obesity and diabetes mellitus and needs aggressive management to reduce cardiovascular risk.
Wierzbicki
A S
AS
Department of Chemical Pathology, St. Thomas' Hospital, London, UK. Anthony.Wierzbicki@kcl.ac.uk
Mikhailidis
D P
DP
Wray
R
R
D000208:Acute Disease; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy* / Q000209:etiology; D007333:Insulin Resistance; D008107:Liver Diseases / Q000150:complications; D009765:Obesity / Q000150:complications; D010195:Pancreatitis / Q000150:complications; D011247:Pregnancy; D011248:Pregnancy Complications
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002995:Clofibric Acid; C006012:fenofibric acid; D011345:Fenofibrate