A Comparison of the Theoretical Relationship between HDL Size and the Ratio of HDL Cholesterol to Apolipoprotein A-I with Experimental Results from the Women's Health Study

Abstract

BACKGROUND HDL size and composition vary among individuals and may be associated with cardiovascular disease and diabetes. We investigated the theoretical relationship between HDL size and composition using an updated version of the spherical model of lipoprotein structure proposed by Shen et al. (Proc Natl Acad Sci U S A 1977;74:837–41.) and compared its predictions with experimental data from the Women's Health Study (WHS). METHODS The Shen model was updated to predict the relationship between HDL diameter and the ratio of HDL-cholesterol (HDL-C) to apolipoprotein A-I (ApoA-I) plasma concentrations (HDL-C/ApoA-I ratio). In the WHS (n = 26 772), nuclear magnetic resonance spectroscopy (NMR) was used to measure the mean HDL diameter (dmean,NMR) and particle concentration (HDL-P); HDL-C and ApoA-I (mg/dL) were measured by standardized assays. RESULTS The updated Shen model predicts a quasilinear increase of HDL diameter with the HDL-C/ApoA-I ratio, consistent with the dmean,NMR values from WHS, which ranged between 8.0 and 10.8 nm and correlated positively with the HDL-C/ApoA-I ratio (r = 0.608, P < 2.2 × 10−16). The WHS data were further described by a linear regression equation: dWHS = 4.66 nm + 12.31(HDL-C/Apo-I), where dWHS is expressed in nanometers. The validity of this equation for estimating HDL size was assessed with data from cholesteryl ester transfer protein deficiency and pharmacologic inhibition. We also illustrate how HDL-P can be estimated from the HDL size and ApoA-I concentration. CONCLUSIONS This study provides a large-scale experimental examination of the updated Shen model. The results offer new insights into HDL structure, composition and remodeling and suggest that the HDL-C/ApoA-I ratio might be a readily available biomarker for estimating HDL size and HDL-P.