Beyond LDL cholesterol: remnant cholesterol is associated with cardiometabolic risk factors in children

Abstract

Background: Recent evidence from both randomized controlled trials and cohort studies in adults suggests that plasma remnant cholesterol (RC) levels predict cardiovascular disease. In children, studies are scarce, although high levels of RC might represent a marker of early atherosclerotic damage. Thus, the aim of this study was to explore the cardiometabolic risk associated with RC, which extends beyond low-density lipoprotein cholesterol (LDL-c) in children.

Methods: Cardiometabolic risk factors (plasma insulin levels, homeostatic model assessment for insulin resistance, mean arterial blood pressure (MAP), waist circumference (WC), and cardiorespiratory fitness (CRF)) were examined in 3417 Spanish schoolchildren aged 8-11 years. The children were categorized into four subgroups (low vs. high) based on the cutoff of ≥ 110 mg/dL for LDL-c and of ≥ 15 mg/dL for RC to define higher levels, and ANCOVA models were applied to assess the role of both lipid parameters in cardiometabolic risk. Additionally, multilevel mixed-effects generalized linear regression models were used to assess the associations of RC or LDL-c with cardiometabolic risk factors and to examine whether the associations between RC and these factors varied in children with low or high LDL-c levels.

Results: Children in the high-RC subgroups, specifically those with low LDL-c/high RC and high LDL-c/high RC, presented significantly greater insulin levels and WC than did their peers in the low-RC subgroups. RC was more strongly associated with cardiometabolic risk factors than LDL-c (insulin β = 2.073/ - 0.026; HOMA-IR β = 0.451/ - 0.002; MAP β = 1.214/0.300; WC β = 2.842/1.058; and CRF β = - 0.316/ - 0.194 for RC and LDL-c, respectively). Furthermore, RC exhibited associations even in children with low LDL-c levels: insulin (β = 2.305; p < 0.001), HOMA-IR (β = 0.499; p < 0.001), MAP (β = 1.397, p < 0.001), WC (β = 2.842; p < 0.001), and CRF (β = - 0.367; p < 0.001).

Conclusions: The associations between RC and cardiometabolic risk factors were stronger than those between LDL-c and cardiometabolic risk, extending its significance even in children with low LDL-c levels. These findings may be clinically useful for cardiovascular risk stratification and for guiding future interventions in children, although they should be confirmed by longitudinal studies.

Keywords: Cardiovascular disease; Childhood; HDL-cholesterol; Triglyceride-rich lipoproteins.

Fig. 1

Scatterplots depicting the relationships between cardiometabolic risk factors and levels of LDL-c and remnant cholesterol (RC) and including Pearson’s correlation coefficient (p value) by sex

Fig. 2

Subgroups of concordance/discordance on levels of low-density lipoprotein cholesterol (LDL-c; mg/dL) and remnant cholesterol (RC; mg/dL) across year of study (observations: the lower part of the figure displays columns illustrating the frequencies of lipid profile subgroups concerning the values of LDL-c and RC)

Fig. 3

Analysis of covariance (ANCOVA) models estimating marginal means of cardiometabolic risk factors by subgroup (lipid profile categories according to low-density lipoprotein cholesterol [LDL-c] and remnant cholesterol [RC] levels)