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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #10 2025

Parallel efforts focus on APOC3 and LPA, addressing residual AAV vectors, ensuring long-term safety of genome editing,
TG and Lp(a)-driven risk. ASOs and siRNAs targeting these achieving precise hepatic targeting, and addressing the Dyslipidaemia
genes have achieved profound biomarker reductions (up to high cost of gene therapies. Continued clinical research
90% for Lp[a]) in early clinical trials. These therapies could and optimisation are essential to realise the transformative
meaningfully impact CV outcomes once long-term data potential of personalised, gene-based approaches in ASCVD
become available. Furthermore, emerging computational tools prevention and lipid management.
complement these therapeutic innovations. PRSs enhance
risk stratification by identifying individuals at intermediate
clinical risk who may benefit most from gene-targeted therapy. CLINICAL PEARLS FROM THE FACULTY
Meanwhile, ML models improve predictive accuracy by
integrating diverse genomic, biochemical, and clinical data,
paving the way for precision CV medicine.

Gene-based therapies represent a paradigm shift in the
management of lipoprotein disorders. Single-course
interventions that permanently silence or correct pathogenic
genes, such as PCSK9 or ANGPTL3, could overcome the
major limitation of poor adherence to chronic LLTs. These
durable strategies are particularly relevant for patients with
severe monogenic dyslipidaemia. The upstream modulation
of atherogenic gene sequences will augment downstream WATCH
innovations in LLT, and when mature and safe enough to be PROF. CHOONG HOU KOH DISCUSS
deployed, will not only be a paradigm shift in ASCVD risk THE CLINICAL RELEVANCE OF THIS
reduction for high-risk populations, but represents a seismic ARTICLE.
jump in our continued efforts in optimising CV health in
primordial and primary prevention.
CLICK HERE
Widespread implementation will depend on overcoming FOR THE LINK TO FULL ARTICLE
key challenges, such as managing immune responses to

TARGETS AND BIOMARKERS

Great debate: Plasma triglycerides are an important causal factor and therapeutic
target for atherosclerotic cardiovascular disease.
Boren J, et al. Eur Heart J. 2025 Jul 14;46(27):2643-2656.

Plasma triglycerides (TG) and triglyceride-rich lipoproteins (TRLs) are recognised as important contributors to ASCVD, but their
precise causal role remains debated. Clinical trials investigating TG-lowering drugs have yielded controversial results, leading to
uncertainty about which TRL component truly drives the residual CV risk observed even after successful LDL-C reduction. This
“Great Debate” reviews the evidence regarding the role of TRLs in ASCVD and through contrasting viewpoints addresses the
fundamental question: should clinicians focus on plasma TG or remnant cholesterol (remnant-C) as the primary risk factor and
therapeutic target?

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