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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #10 2025

Human genetic lipid phenotypes in relation to development of atherosclerosis Dyslipidaemia

Because these human genetic lipid phenotypes are driven by genetic variation free from confounding and reverse causation, these conditions illustrate the causal
relationship from respectively elevated LDL, chylomicrons, and remnants to risk of myocardial infarction and ASCVD. mM, mmol/L; Chol, plasma cholesterol. To
convert cholesterol values to mg/dL, multiply values in mmol/L with 38.6. To convert triglyceride values to mg/dL, multiply values in mmol/L with 88.

Studies from human genetic lipid phenotypes provide evidence cholesterol, TG, HDL-C, LDL-C, remnant-C, and non-HDL-C,
that supports the CONTRA argument. FCS, characterised by preferably measured in the non-fasting state to better capture
elevated plasma TG carried in large chylomicrons, does not the average TRL/remnant load throughout the day.
lead to ASCVD because the particles are too large to cross
the endothelial barrier into the arterial intima. Conditions like
familial hypercholesterolaemia (characterised by high LDL-C) CLINICAL PEARLS FROM THE FACULTY
and familial remnant hyperlipidaemia (high remnant-C) cause
accelerated ASCVD because the particles are small enough to
enter the arterial wall. This contrast demonstrates that particle
size and cholesterol content dictate atherogenicity. Furthermore,
large epidemiological studies show that the strong association
between elevated plasma TG and ASCVD risk disappears
completely when adjusted for lipoprotein cholesterol content,
including remnant-C. Therefore, focusing on remnant-C
simplifies the clinical message, aligning it with the established
paradigm of reducing LDL-C.

Regardless of the debate over which component is strictly
causal, the authors on both sides of the debate agree that TRL- WATCH
associated risk must be addressed, and current risk assessment PROF. AHMED SHAWKY DISCUSS
requires improvement. For clinical practice, the key takeaway is THE CLINICAL RELEVANCE OF THIS
that lowering TG may not be clinically relevant unless it results ARTICLE.
in a significant reduction in the number of atherogenic particles,
typically measured via apoB levels. Non-HDL-C and/or apoB
are currently considered the best metrics for assessing CV risk CLICK HERE
beyond LDL-C goals. A consensus recommendation is that the FOR THE LINK TO FULL ARTICLE
optimal laboratory report should include six components: total

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