Abstract 11297: Longitudinal Lipidomics Profiling of Risk for Hypertension in American Indians: The Strong Heart Study

Abstract

Background: Dyslipidemia is an important risk factor for hypertension (HTN). Routine clinical tests cannot capture all molecular lipid species in blood (i.e., lipidome). Moreover, a longitudinal lipidomic profiling of risk for HTN is still lacking in any racial/ethnic groups. Objective: Identify novel lipid species and lipidomic signatures associated with risk of HTN in American Indians, independent of traditional risk factors (TRFs). Methods: Using an untargeted LC-MS, we repeatedly measured 1,542 lipids in 3,916 fasting plasma samples from 1,958 American Indians attending two clinical examinations (~5.5 years apart) in the SHS. Elastic net was used to select baseline lipids associated with risk of HTN. Longitudinal associations between changes in lipidome and changes in blood pressure measures, e.g., SBP, DBP, mean arterial pressure (MAP), were examined by mixed-effect linear model, adjusting for TRFs and baseline lipids. Multivariate and network analysis was used to identify lipidomic signatures and differentially co-regulated lipid pairs associated with risk of HTN. Results: Of 905 normotensive participants at baseline, 276 developed HTN after 5-year follow-up. After adjusting for TRFs (age, age 2 , sex, center, BMI, smoking, and diabetes), higher baseline levels of 144 lipids (38 known), including glycerophospholipids, glycerolipids, acylcarnitines, sphingolipids, and fatty acids, were significantly associated with increased (HRs:1.03- 2.07) or decreased (HRs: 0.80 - 0.94) risk of HTN. A lipid score comprising 38 baseline lipids significantly improved risk prediction beyond TRFs (ROC increases from 0.678 to 0.725, P<0.001). Longitudinal change in plasma lipidome explains up to 3.2% variability in changes of BP measures. Multivariate and network analysis identified lipidomic signatures and differentially regulated lipid networks associated with risk of HTN. Conclusion: We identified novel molecular lipids and lipidomic signatures associated with risk of HTN, independent of TRFs. If replicated, the newly identified molecular lipids may serve as novel biomarkers for risk stratification and provide therapeutic targets for early intervention tailored to American Indians.