title: Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol.
abstract: Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceride-rich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events.
authors.affiliation: Departments of Medicine and Physiology and the Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Changting
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Departments of Medicine and Physiology and the Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Satya
authors.initials: S
authors.lastname: Dash
authors.affiliation: Departments of Medicine and Physiology and the Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.affiliation: Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Departments of Medicine and Physiology and the Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada gary.lewis@uhn.ca.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents