Correlations Between Cardiovascular Disease Risk Factors and Lipid Metabolic Pathways

A multiplexed, quantitative analytical workflow was applied to 120 fasting human serum samples collected from 30 normolipidemic, and 90 dyslipidemic donors. The analysis included separation by asymmetric flow field-flow fractionation while collecting fractions with ~1 nm increments of 7-15 nm (HDL), 20-30 nm (LDL) and greater than 30 nm lipoproteins. Size separation was followed by concentration measurements in each size fraction for non-polar lipids (FC, CE and TG), polar lipids (PC, SM, PE and PI), and apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E); using three parallel, high throughput, quantitative liquid chromatography-tandem mass spectrometry methods developed in our laboratory. The average hydrodynamic size in each size fraction was also determined by dynamic light scattering. Measuring all major lipid and protein components and the size in all fractions allowed volumetric estimation of lipoprotein particle numbers (Lp-P). In the LDL size range of 22-26 nm, the calculated mean (N=120 samples) of the average (N=5 fraction/sample) apoB/LDL-P was 1.00 (Stdev=0.31, N=120). The resulting highly comprehensive data set allowed the evaluation of correlations between cardiovascular disease (CVD) risk factors and metabolic pathway specific indicators. For example, multivariate modelling of Total-TG/HDL-C ratios (1.5-17.5) showed negative correlation with HDL-apoC-III/LDL-apoC-III ratios.