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.