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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #11 2026

The HDL-C U-shaped curve Dyslipidaemia

EmCAD, Emory Cardiovascular Biobank; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratio; UKB, United Kingdom Biobank.

However, recent evidence reveals a potentially “harmful” with elevated baseline LDL-C. Additionally, there is ongoing
U-shaped relationship, where extremely high HDL-C levels research into next-generation cholesteryl ester transfer protein
(>80 mg/dL) are paradoxically associated with a significantly (CETP) inhibitors like obicetrapib, which is being investigated in
increased risk of all-cause and CV mortality. This harm is the TANDEM trial as a fixed-dose combination with ezetimibe to
thought to occur because HDL particles can become chronically aggressively manage lipid levels.
dysfunctional during acute phases or oxidative stress, losing
their protective benefits and instead impairing endothelial Conditions with effect on HDL-C
function or exhibiting proinflammatory effects. and their corresponding CV risk

Despite the failures of traditional medications designed merely to
increase HDL-C quantities, researchers remain “hopeful” about
novel therapies that actively target HDL function, particularly
its cholesterol efflux capacity. For example, apolipoprotein A-I
(apoA-I) infusions such as CSL112 have shown promise in
reducing the long-term burden of ischaemic events in post-MI
patients who have elevated baseline LDL-C. While the recent
AEGIS-II trial did not meet its short-term 90-day endpoints,
exploratory analyses suggest these infusions might reduce the
longer-term burden of ischaemic events, especially in patients

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