Physicians' Academy for Cardiovascular Education

Increased atherogenicity of LDL and impaired HDL function in children with FH

News - June 7, 2021

Children with FH display changes in LDL and HDL function: a cross-sectional study

Presented at EAS 2021 by Jacob Christensen, PhD (Oslo, Norway)

Introduction and methods

The function of lipoproteins is emerging as an important risk factor in the progression of ASCVD. The intrinsic property of LDL to aggregate upon modification, for instance, is associated with ASCVD. Also, HDL function, which can be quantified by measuring cholesterol efflux capacity, is associated with risk for ASCVD. However, whether children with familiar hypercholesterolemia (FH) have altered lipoprotein particle functions is unknown.

This study assessed LDL and HDL function and activity of four enzymes that are involved in lipoprotein metabolism in plasma samples from children with FH (13±4 years; n=47) and healthy children (10±2 years, n=56).

LDL function was determined by measuring the susceptibility of LDL to form aggregates by induction with human recombinant sphingomyolinase. HDL function was assessed with a HDL-apoA-I exchange (HAE) assay. This assay uses electron paramagnetic resonance spectroscopy which captures the conformational changes that apoA-I undergoes upon direct association or dissociation with HDL particles and correlates with cholesterol efflux capacity. Also, enzyme activity of LCAT, CETP, PLTP, and PON1 was analyzed. The potential biological mechanism behind variations in lipoprotein function was further explored using a nuclear magnetic resonance based metabolomics profiling approach.

Main results


Children with FH had LDL particles with an increased atherogenicity and impaired function of HDL compared to healthy children.

Christensen suggested at the end that alterations in LDL receptor function, plasma LDL concentrations, and the cumulative cholesterol burden in FH may jointly be the overarching drivers and common denominators linking these metrics in a biologically relevant context.

-Our reporting is based upon the information provided at the EAS 2021 congress-

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