Relationship of Apolipoproteins and Subclinical Cardiovascular Risk in Children and Adolescents

Abstract

INTRODUCTION: Apolipoproteins play a role in regulating cholesterol transportation and clearance with each apolipoprotein having a protective or atherogenic role. However, previous literature in youth have insufficiently described the relationship between each apolipoprotein variable and subclinical cardiovascular risk. Hence, the purpose of this study was to examine the association of apolipoproteins with measures of vascular structure and function in children and adolescents. METHODS: A cross-sectional study of 338 youth (160 males, 178 females; mean age = 13.0+/-2.8 years) with a range of adiposities from normal body weight to severe obesity. Apolipoproteins (AI, AII, B100, CII, CIII, and E) were measured via human apolipoprotein magnetic bead panel. Ultrasound imaging of the carotid artery was used to measure carotid intima-media thickness (cIMT), carotid cross-sectional compliance (cCSC), carotid diameter compliance (cDC), carotid cross-sectional distensibility (cCSD), carotid diameter distensibility (cDD), and carotid incremental elastic modulus (cIEM). Applanation tonometry assessed pulse wave velocity (PWV). Dual X-ray absorptiometry measured total body fat percent. Linear regression models were adjusted for Tanner stage, sex, and race with further adjustments for body fat percent. Data are presented as mean [95% CI] with Holm’s-adjusted p-values to account for multiple testing. All apolipoproteins were scaled to 10 ug/mL and apolipoprotein ratios were scaled to 0.1 ug/mL. RESULTS: Prior to accounting for multiple testing, apolipoprotein CIII:CII ratio was positively associated with cIMT (0.001 [0, 0.003], p = 0.033), but failed to maintain significance after p-value correction. Otherwise, there were no significant associations between any apolipoprotein and cIMT, cCSC, cDC, cCSD, cDD, and cIEM in the presence or absence of body fat percent. There were significant positive associations between PWV and apolipoproteins: AII (0.04 m/sec [0.02, 0.06], p = 0.046) and E (0.16 m/sec [0.08, 0.24], p = 0.012). After adding body fat percent to the models, PWV remained positively associated with higher levels of apolipoproteins E (0.16 m/sec [0.08, 0.24], p = 0.01). CONCLUSIONS: These findings suggest higher levels of apolipoprotein E are associated with higher arterial stiffness (PWV) in pediatrics, both in the presence and absence of excess body fat.