Hypertriglyceridaemia and its multifaceted mechanisms driving atherosclerotic cardiovascular disease

Emerging evidence has shown that hypertriglyceridaemia (HTG) is a significant independent residual risk factor for atherosclerotic cardiovascular disease (ASCVD), even with optimal low density lipoprotein cholesterol (LDL-C) management. Although its direct causal role in atherogenesis remains debatable, recent mechanistic insights have unveiled novel proatherogenic pathways associated with HTG. This review critically synthesises and updates the evolving evidence linking HTG to atherosclerotic pathogenesis. Here, we describe multiple mechanisms by which HTG contributes to the initiation and progression of atherosclerotic plaques. These include promotion of subendothelial cholesterol retention, induction of vascular inflammation and endothelial dysfunction, acceleration of arterial aging, and promotion of prothrombosis. Integrating these contemporary insights, this review outlines a refined scientific framework that posits that HTG is a crucial modifiable residual risk factor for ASCVD. This paradigm enables more comprehensive risk stratification and informs the development of targeted therapies to complement conventional lipid-lowering treatments.