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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #10 2025

Graphical abstract Dyslipidaemia

FCS, familial chylomicronaemia syndrome; FH, familial hypercholesterolaemia; HDL, high-density lipoprotein; LDL, low-density lipoprotein;
remnant-C, remnant cholesterol; TG, triglyceride; TRL, triglyceride-rich lipoprotein.

The PRO argument posits that plasma TG serves as a crucial, higher odds ratio for CVD compared to LDL-C per unit change.
easily measured biomarker for the abundance of TRLs and This differential risk implies that properties beyond just the
their remnants in circulation. Although TG itself is not retained cholesterol content of the particle must account for their
in atherosclerotic plaques, measuring plasma TG is considered stronger association with CVD risk, for example the presence
a suitable surrogate for TRL abundance. The PRO argument of apolipoprotein C3 (APOC3) which triggers inflammation.
emphasises that TRLs are structurally heterogeneous and Therefore, relying solely on remnant-C as the causal risk factor
interact with the arterial wall through multiple, complex could overlook the full, integrated atherogenic impact driven by
pathogenic mechanisms, which are not fully captured by the diverse composition and inflammatory actions of TRLs.
cholesterol content alone. This complexity includes the release
of proinflammatory mediators (free fatty acids [FFAs]) during TG In contrast, the CONTRA argument maintains that remnant-C is
hydrolysis in the arterial intima, altering endothelial function and the causal factor for ASCVD. This view is based on pathological
contributing to plaque vulnerability. analysis showing that atherosclerotic plaques accumulate
cholesterol, which cannot be degraded by arterial cells.
Another crucial component is evidence from genetic studies, However, when TRL remnants enter the arterial intima, their TG
which suggests that TRL/remnant particles are about four content is rapidly degraded into FFAs and monoacylglycerol,
times more atherogenic than LDL particles. Genetic variations which do not contribute to plaque volume. Therefore, elevated
predicting elevated TRL/remnant-C are associated with a plasma TG is highly correlated with remnant-C but not the true
cause of cholesterol accumulation.

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