HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study

Monika Hunjadi,Andreas Ritsch,Tamara Bernscherer,Claudia Lamina,Mikko Hurme,Päivi Tossavainen,Patrick Kahler,Jorma Viikari,Mika Kähönen,Leena Taittonen,Olli Raitakari,Eero Jokinen,Terho Lehtimäki,Tomi Laitinen,Markus Juonala,Nina Hutri-Kähönen

doi:10.1038/s41598-020-76146-7

Abstract

The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated 3H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial structure and function. CEC was higher in women, correlated with total cholesterol, HDL-C, and apolipoprotein A-I, but not with LDL-C or apolipoprotein B. Compared to the lowest CEC quartile, the highest CEC quartile was significantly associated with high CRP levels and inversely associated with adiponectin. At baseline, high CEC was associated with decreased flow-mediated dilation (FMD) and carotid artery distensibility, as well as an increased Young's modulus of elasticity, indicating adverse changes in arterial structure, and function. The association reversed with follow-up FMD data, indicating the interaction of preclinical parameters over time. A higher CEC was directly associated with a lower risk of subclinical atherosclerosis at follow-up. In young and healthy subjects, CEC was associated with important lipid risk parameters at baseline, as in older patients and CAD patients, but inversely with early risk markers for subclinical atherosclerosis.

Highlights

The atherogenic process begins already in childhood and progresses to symptomatic condition with age
Serum samples from 2282 individuals from the 2001 follow-up of the Young Finns study were available for measurement of cholesterol efflux capacity (CEC)
We investigated parameters influencing CEC including lipid parameters, basic clinical parameters, and classical risk factors for cardiovascular disease (CVD) in a large cohort of young and healthy subjects

Summary

Introduction

The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. Abbreviations apo Apolipoprotein CEC Cholesterol efflux capacity CVD Cardiovascular disease DPM Disintegrations per unit time HDL High-density lipoprotein LDL Low-density lipoprotein Lp(a) Lipoprotein (a) TG Triglycerides FMD Flow-mediated dilation IMT Intima-media thickness CDist Carotid artery distensibility YEM Young’s elastic modulus YFS The Cardiovascular Risk in Young Finns Study. A key function of HDL is the ability to promote the efflux of unesterified cholesterol from peripheral cells within the so-called HDL mediated reverse cholesterol transport This process is considered atheroprotective by transferring excess cholesterol from the periphery, such as the arterial wall, back to the liver where it is secreted into the bile or converted into bile acids. The objective of this study was twofold: first to investigate the effect of known atherosclerotic risk factors and other lipoprotein parameters on CEC within healthy young individuals; and second to evaluate the effects of CEC on preclinical parameters of atherosclerosis, independently of known risk factors, in one of the largest prospective population-based study on initially healthy young individuals

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