Prebeta-1 HDL and Assessment of CVD Risk in Overweight/Obese Children

Presentation Number: MON 508
Date of Presentation: April 3rd, 2017

Christine T Ferrara*1, Joshua W Tarkoff2, John P. Kane3 and Mary Malloy3
1University of California, San Francisco, San Francisco, CA, 2Nicklaus Chilldren’s Endocrinology, Miami, FL, 3University of California - San Francisco, San Francisco, CA


Atherosclerotic cardiovascular disease (CVD)continues to be the leading cause of death and disability in the industrialized world. Current screening and management algorithms for pediatric dyslipidemia are based on the fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides (TG)), but fail to incorporate lipoprotein subspecies that may be clinically significant. In the adult population, prebeta-1 HDL, a molecular species of HDL involved in reverse cholesterol transport, is an independent and perhaps superior predictor of CVD in non-diabetic adults than traditional fasting lipid measurements (1). While efforts to uncover novel lipoprotein biomarkers in adults continue, there is a paucity of studies in the pediatric population.

In order to characterize reverse cholesterol transport in children at risk for CVD, we measured prebeta-1 HDL in overweight/obese pediatric subjects, and analyzed the relationship of this biomarker to elements of the traditional lipid profile. A total of 60 subjects age 3-18 (mean 11.02) with BMIZ from 1.38-4.28 (mean 2.42) were included in this study, among whom 60% had dyslipidemia based on a fasting lipid profile. Seventy percent of subjects had additional components of metabolic syndrome beyond obesity (dysglycemia, hypertension, low HDL, elevated TG).

Among the traditional lipid measurements, TG and LDL-C were positively associated with prebeta-1 HDL levels, even after adjusting for age, ethnicity, and BMIZ (p=0.002, 0.000 respectively). Despite no differences in prebeta-1 HDL, total cholesterol, LDL-C, TG, or HDL-C levels between males and females, stratified analysis demonstrated sex-specific differences in the association of prebeta-1 HDL and these lipid components. In male subjects, prebeta-1 HDL was associated only with TG (p=0.001); in females it was associated with only with LDL-C (p=0.011). HDL-C was not independently associated with prebeta-1 HDL in this cohort, but importantly, HDL-C levels modified the effect of TG on prebeta-1 HDL (p interaction=0.003). An HDL-C level below 40mg/dl augmented the association of elevated TG with increased prebeta-1 HDL levels, while those with HDL-C >40mg/dl were protected from this effect. Older age (>11.5 years) and Hispanic ethnicity enhanced the ability of TG to increase prebeta-1 HDL, demonstrating key interactions among demographic covariates

These data suggest that in pediatrics, interpretation of a fasting lipid profile should include an assessment of several lipid biomarkers as well as clinical data including age, sex, and ethnicity. Future studies are needed to characterize prebeta-1 HDL levels in non-obese children and other pediatric populations at risk for CVD to determine whether new dyslipidemia thresholds are needed to guide treatment algorithms.


Nothing to Disclose: CTF, JWT, JPK, MM