The metabolic and pharmacologic bases for treating atherogenic dyslipidaemia.
Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is characterized by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed high-density lipoprotein (HDL) and increased small dense low-density lipoprotein (LDL) particle concentrations. Dysregulation of lipoprotein metabolism in the metabolic syndrome may be due to a combination of overproduction of very-low density lipoprotein (VLDL) apoB, decreased catabolism of apoB-containing particles, and increased catabolism of HDL apoA-I particles. These abnormalities are due to a global metabolic effect of insulin resistance and visceral obesity. Lifestyle modifications (dietary restriction and increased exercise) and pharmacological treatments favourably alter lipoprotein transport by decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL apoA-I, as well as by increasing the clearance of LDL-apoB. The safety and tolerability of combination drug therapy based on statins is important and merits further investigation. There are several pipeline therapies for correcting triglyceride-rich lipoprotein and HDL metabolism. However, their clinical efficacy, safety and cost-effectiveness remain to be demonstrated.
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Dick C
DC
Chan
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia.
P Hugh R
PH
Barrett
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Lipid Disorders Clinic, Royal Perth Hospital, Perth, Australia. Electronic address: gerald.watts@uwa.edu.au.
Gerald F
GF
Watts
D050197:Atherosclerosis / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D004032:Diet; D050171:Dyslipidemias / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D020022:Genetic Predisposition to Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008019:Life Style; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism / Q000628:therapy; D012307:Risk Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins
Cardiovascular disease; Hypertriglyceridaemia; Lifestyle modification; Low-HDL-cholesterol; Metabolic syndrome; Pharmacological treatment; Treatment target