Children with familial hypercholesterolemia display changes in LDL and HDL function: A cross‐sectional study

Abstract Background The function of high-density lipoprotein (HDL) cholesterol may play a more important role in the prevention of cardiovascular disease compared to the concentration of the HDL. Cardiovascular diseases such as coronary artery disease (CAD) and atrial fibrillation (AF) have been linked to impaired HDL function. Purpose The aim of the present study is to assess a biochemical measure of the antioxidant function of HDL and its association with presence of CAD and AF. Methods Patients admitted for elective cardiac catheterization were recruited in this cross-sectional study. Out of 1231 participants that were included in the analyses, 727 patients had confirmed CAD (CAD group), 369 patients had no CAD (no CAD group) and 129 persons were included as a control group. HDL function was measured in sera by determination of HDL-lipid peroxidation content (HDLox) assessed by a validated fluorometric cell-free biochemical assay and was normalized for the levels of HDL cholesterol (normalized HDLox/HDL-C ratio or nHDLox; no units). Results are expressed as median with interquartile range. Associations of nHDLox with presence of CAD and AF were assessed by univariate and multivariate analyses. Results Participants in the CAD group had higher levels of nHDLox (0.80, 0.61–1.03) compared to the no CAD (0.70, 0.55–0.93) and control (0.66, 0.55–1.03, no units, p<0.001) group. Out of 1206 participants, 233 (19%) had AF and 973 (81%) had no AF. Patients with AF have also higher nHDLox (0.82, 0.60–10.03) compared to persons without AF (0.73, 0.58–0.98, p=0.03). In univariate analysis nHDLox was associated with CAD (p<0.001). In multivariate analysis adjusted for age, gender, CAD, BMI and hypertension, nHDLox was a strong independent predictor of atrial fibrillation (p=0.015) but was not an independent predictor of CAD (p>0.05) Conclusions Reduced antioxidant function of HDL (increased HDLox measured by a biochemical assay), a metric of HDL function, is increased in patients with atherosclerosis and manifested CAD and is also associated with the presence of atrial fibrillation independent of the presence of CAD. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Medical School of Brandenburg-MHB Fontane

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Comprehensive lipid and metabolite profiling of children with and without familial hypercholesterolemia: A cross-sectional study

Atherosclerosis ◽

10.1016/j.atherosclerosis.2017.09.021 ◽

2017 ◽

Vol 266 ◽

pp. 48-57 ◽

Cited By ~ 10

Author(s):

Jacob J. Christensen ◽

Stine M. Ulven ◽

Kjetil Retterstøl ◽

Ingunn Narverud ◽

Martin P. Bogsrud ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Metabolite Profiling ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional

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Clinical Characteristics, Lipid Treatment and Goal Attainment in a Familial Hypercholesterolemia Cohort in The Netherlands: a Cross Sectional Study

Value in Health ◽

10.1016/j.jval.2015.09.799 ◽

2015 ◽

Vol 18 (7) ◽

pp. A379

Author(s):

JG Kuiper ◽

EM Heintjes ◽

E Houben ◽

FJ Penning-van Beest ◽

RJ Sanchez ◽

...

Keyword(s):

The Netherlands ◽

Familial Hypercholesterolemia ◽

Clinical Characteristics ◽

Goal Attainment ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional

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

10.1101/2020.11.11.20214247 ◽

2020 ◽

Author(s):

Jacob J. Christensen ◽

Ingunn Narverud ◽

Maija Ruuth ◽

Martin Heier ◽

Matti Jauhiainen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Familial Hypercholesterolemia ◽

Lipoprotein Metabolism ◽

Cross Sectional Study ◽

Mirror Image ◽

Atherosclerotic Cardiovascular Disease ◽

Healthy Children ◽

Cross Sectional ◽

Ldl Particles ◽

Hdl Function

AbstractBackgroundThe functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma LDL particles to aggregate and the ability of HDL particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations.HypothesisWe hypothesized that FH children had disrupted lipoprotein function.MethodsWe analyzed LDL aggregation susceptibility and HDL-apoA-I exchange to apoA-I ratio (HAE/apoA-I ratio), and activity of four proteins that regulate lipoprotein metabolism (CETP, LCAT, PLTP and PON1) in plasma samples derived from children with FH (n = 47) and from healthy children (n = 56). Potential biological mechanisms behind any variation in lipoprotein functionalities were explored using an NMR-based metabolomics profiling approach.ResultsLDL aggregation was higher and HAE/apoA-I ratio was lower in FH children than in healthy children. LDL aggregation associated positively with LDL-C and negatively with triglycerides, and HAE/apoA-I ratio associated negatively with LDL-C. Generally, the metabolomic profile for LDL aggregation was a mirror image of that for HAE/apoA-I ratio.ConclusionsFH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL may increase the risk for atherosclerotic cardiovascular disease in FH children.

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