(P21-005-25) Low Density Lipoprotein Lipidomic Differences in Cholesterol-Stratified Atherosclerosis Risk Groups

Objectives: This study will characterize global differences in plasma lipid composition in age, sex and body mass matched participants stratified into high and low atherosclerotic risk groups by low density lipoprotein cholesterol (LDLc) levels.

Methods: A set of fasting plasma samples (n = 40) from sex (20 female/20 male) and BMI (18-39) matched pairs within 2 years of age (23 to 65) with LDLc of < 100 mg/dL (low-risk) or >160 mg/dL (high-risk) were selected from the USDA Western Human Nutrition Research Center Cross-Sectional Nutritional Phenotyping Study (Clinical Trials: NCT02367287). The profile of 500+ lipids from 36 lipid classes was quantified by LC-MS/MS using minor modifications of published procedures. Group segregation was evaluated by partial least squares discriminate analysis (PLS-DA), and group mean lipid levels were compared by t-tests with adjustment by sex, BMI, and age and false discovery rate multiple comparison corrections.

Results: PLS-DA of plasma lipidomics can discriminate Low Risk and High-Risk groups (Q2 =0.525; X² =0.426; Y² =0.980). The High-Risk group showed higher levels of sphingolipids, lysophospholipids and di- and tri-acyl glycerides, but lower levels of ether-linked phospholipids (i.e. plasmalogens).

Conclusions: These findings demonstrate that a broad array of plasma lipids vary between LDLc-stratified atherogenic risk groups. High risk is associated with lower levels of oxidative stress-sensitive plasmalogens and higher levels of proatherogenic sphingolipids, among other changes. Future efforts will investigate the distribution of these lipids within lipoprotein particle subclasses and associated changes in apolipoproteins.

Funding Sources: USDA