Abstract 12762: Plasma Lipidomic Signature of Peripheral Artery Disease in Young and Middle-Aged American Indian Individuals: The Strong Heart Family Study

Abstract

Introduction: Dyslipidemia is an independent risk factor for peripheral artery disease (PAD). Ankle-brachial index (ABI) is a sensitive and cost-effective tool for screening and predicting PAD. The association between individual lipid species and the progression in subclinical PAD, assessed by change in ABI, remains to be determined, especially in understudied populations at high risk. Hypothesis: To identify individual molecular lipid species associated with PAD progression in American Indians, independent of traditional risk factors. Methods: Using an untargeted lipidomic method by liquid chromatography-mass spectrometry, we repeatedly measured 1,542 individual lipid species in 2,830 fasting plasma samples at two time points (2001-2003 and 2006-2009, mean 5 years apart) from 1,415 unique American Indians in the Strong Heart Family Study. Participants were free of prevalent PAD at both time points. ABI was measured in the right arm and bilateral (both left and right posterior tibial artery) using a handheld Doppler and was analyzed as a continuous variable. We first identified baseline lipid species associated with change in ABI by generalized estimating equation models, adjusting for baseline age, sex, BMI, smoking, eGFR, diabetes, hypertension, lipid-lowering medication and baseline ABI. We then examined the longitudinal association between change in lipid species and change in ABI, adjusting for same covariates plus baseline lipids. Results: Participants (63% female) were aged between 18-65 (mean 38) at baseline and 22-72 (mean 43) at follow-up. Higher baseline levels of 36 lipid species were positively (ORs: 1.01 - 3.60), whereas 16 lipid species were inversely (ORs: 0.26 - 0.98), associated with change in ABI. Longitudinal changes in 77 lipid species, largely glycerolipids, glycerophospholipids, and sphingolipids, were significantly associated with change in ABI during 5-year follow-up. Conclusions: Baseline plasma lipid species and their longitudinal changes over time are significantly associated with PAD progression beyond known risk factors. These findings shed light on the role of dyslipidemia in PAD among young and middle-aged American Indians who suffer high rates of obesity, diabetes and other cardiometabolic disorders.