Abstract 11325: Lipidomics Profiling of Risk for Subclinical Atherosclerosis: A Longitudinal Study in American Indians in the Strong Heart Study

Abstract

Background: Dyslipidemia is an established risk factor for atherosclerotic CVD, but full identification of circulating molecular lipids associated with atherosclerosis is still lacking in any racial/ethnic group. Objective: Prospectively identify lipid species associated with risk of atherosclerosis in American Indians. Methods: Using an untargeted LC-MS, we repeatedly measured 3,891 paired fasting plasma samples from 1,950 American Indians at two exams (~5.5 year apart) in the Strong Heart Family Study. Carotid atherosclerosis was assessed by carotid ultrasonography. Incident carotid atherosclerosis was identified if plaque was absent at baseline but detected at follow-up. Elastic net model was used to select baseline lipids or change in lipids (baseline to follow-up) associated with risk for atherosclerosis beyond traditional risk factors (TRFs) including age, sex, center, smoking, BMI, hypertension, diabetes, LDL-c and albuminuria. Multivariate analysis was used to identify lipidomic signatures associated with risk for carotid atherosclerosis. Results: Of 1,319 participants with no evident plaque at baseline (2001-2003), 270 developed incident carotid atherosclerosis at 5-year follow-up (2006-2009). Of 518 known lipids detected, altered baseline levels of 29 lipid species, largely glycerophospholipids and glycerolipids, were significantly associated with risk of atherosclerosis beyond TRFs (HR: 1.06-1.33 for risk lipids; 0.85-0.93 for protective lipids). A lipid score comprising top 5 baseline lipids improves risk prediction beyond TRFs (ROC increases from 0.79 to 0.80, P = 0.03). Longitudinal changes in 20 lipids, mainly glycerophospholipids, were significantly associated with risk of atherosclerosis after adjusting for TRFs and baseline lipids. Multivariate analysis identified distinct lipidomic signatures associated with atherosclerosis. Conclusion: Altered baseline lipids were independently associated with prevalent and incident carotid atherosclerosis in American Indians. Our findings shed light on the mechanisms linking dyslipidemia to atherosclerosis and provide instrumental data for risk stratification and therapeutic targets customized to American Indians.