[Residual risk: The roles of triglycerides and high density lipoproteins]

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Lipid Metabolism

Background:

• Statins significantly reduce cardiovascular events but leave residual risk.
• High triglycerides and low HDL cholesterol are implicated in residual cardiovascular risk.
• The roles of triglycerides and HDL in cardiovascular disease are complex and often inversely correlated.

Purpose of the Study:

• To re-evaluate the importance of triglycerides versus HDL cholesterol in residual cardiovascular risk.
• To identify specific conditions where high triglycerides are atherogenic.
• To explore novel therapeutic targets for managing residual cardiovascular risk.

Main Methods:

• Analysis of clinical trial data on statin efficacy and residual risk.
• Review of genetically-epidemiological studies on lipoprotein metabolism.
• Examination of intervention studies with cholesteryl ester transfer protein inhibitors.
• Investigation into the role of apolipoprotein C3 in triglyceride and remnant metabolism.

Main Results:

• The importance of HDL cholesterol may have been overestimated, while triglycerides have been underestimated.
• High triglycerides are atherogenic primarily when associated with cholesterol-enriched remnants (e.g., familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus).
• Inhibiting apolipoprotein C3 expression normalizes triglyceride and remnant concentrations.

Conclusions:

• Managing residual cardiovascular risk requires a nuanced understanding of lipid metabolism.
• Targeting triglyceride-rich lipoproteins and their remnants is a promising therapeutic avenue.
• Inhibition of apolipoprotein C3 represents a novel and potentially effective strategy for cardiovascular risk reduction.