The metabolic and pharmacologic bases for treating atherogenic dyslipidaemia.

Abstract

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.

• Authors: Dick C Chan, P Hugh R Barrett, Gerald F Watts
• Journal: Best practice & research. Clinical endocrinology & metabolism (Best Pract Res Clin Endocrinol Metab) Vol. 28 Issue 3 Pg. 369-85 (Jun 2014) ISSN: 1878-1594 [Electronic] Netherlands
• PMID: 24840265 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Lipoproteins

Topics

• Atherosclerosis (complications, genetics, metabolism, therapy)
• Cardiovascular Diseases (blood, etiology, prevention & control)
• Diet
• Dyslipidemias (complications, genetics, metabolism, therapy)
• Genetic Predisposition to Disease
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Life Style
• Lipoproteins (drug effects, metabolism)
• Metabolic Syndrome (metabolism, therapy)
• Risk Factors