Hypertriglyceridaemia and its multifaceted mechanisms driving atherosclerotic cardiovascular disease​​

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Atherosclerosis Research

Background:

• Hypertriglyceridaemia (HTG) is recognized as a significant independent residual risk factor for atherosclerotic cardiovascular disease (ASCVD).
• Despite optimal low-density lipoprotein cholesterol (LDL-C) management, HTG persists as a critical concern for cardiovascular health.
• Novel mechanistic insights highlight proatherogenic pathways linked to HTG, prompting a re-evaluation of its role in atherogenesis.

Purpose of the Study:

• To critically synthesize and update the evolving evidence linking HTG to atherosclerotic pathogenesis.
• To elucidate the multiple mechanisms through which HTG contributes to the initiation and progression of atherosclerotic plaques.
• To propose a refined scientific framework positioning HTG as a crucial modifiable residual risk factor for ASCVD.

Main Methods:

• Literature review and synthesis of emerging evidence on HTG and ASCVD.
• Analysis of mechanistic insights into proatherogenic pathways associated with HTG.
• Integration of contemporary findings to develop a refined scientific framework.

Main Results:

• HTG promotes subendothelial cholesterol retention, a key step in atherogenesis.
• HTG induces vascular inflammation and endothelial dysfunction, contributing to plaque development.
• HTG accelerates arterial aging and promotes a prothrombotic state, further increasing ASCVD risk.

Conclusions:

• HTG is a crucial modifiable residual risk factor for ASCVD, acting through multiple proatherogenic mechanisms.
• A refined understanding of HTG's role enables more comprehensive cardiovascular risk stratification.
• Targeted therapies addressing HTG are essential to complement conventional lipid-lowering treatments for ASCVD prevention.