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Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case-control study.

ABSTRACT: Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case-control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.

SUBMITTER: Sanz JM

PROVIDER: S-EPMC10209072 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case-control study.

Sanz Juana Maria JM D'Amuri Andrea A Sergi Domenico D Angelini Sharon S Fortunato Valeria V Favari Elda E Vigna Giovanni G Zuliani Giovanni G Dalla Nora Edoardo E Passaro Angelina A

Scientific reports 20230524 1

Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, ...[more]

PMID: 37225774

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Project description:BackgroundAlthough HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity-a prototypical measure of HDL function-has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain.MethodsWe measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40-79 years, assessed in 1993-97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants.FindingsCholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=-0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51-0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70-0·90) for a per-SD change in cholesterol efflux capacity.InterpretationHDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease.FundingUS National Institutes of Health, UK Medical Research Council, Cancer Research UK.

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Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case-control study.

Publications

Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case-control study.

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